{"id": "CaseReportBench:train-511", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Presentation': 'A 22-year-old Hispanic female with a past medical history of dysmenorrhea and recurrent urinary tract infections (UTIs), previously diagnosed by her primary care physician, presented with an 8-day history of no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation. She had tried multiple laxatives for symptom relief. She also reported frequent antibiotic usage, most recently ciprofloxacin, for recurrent UTIs. She had previously been prescribed an oral contraceptive for dysmenorrhea, but it was recently discontinued due to severe nausea and negligible improvement of her abdominal pain. On presentation, she was afebrile (36.7°C), had a normal heart rate (85 beats per minute), normal respiratory rate (16 breaths per minute), and was normotensive (121/80 mmHg). On physical examination, the patient was alert and oriented to time, place, and person without any objective signs of anxiety, depression, psychosis, or other appreciable psychiatric disturbances. The abdomen was soft, nondistended, with mild upper abdominal and periumbilical tenderness. Laboratory examinations were remarkable only for hyponatremia of 130 mEq/L and hypoalbuminemia at 3.4 g/dL. Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm/kg and urine sodium was 100 mEq/L, indicating a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Her initial computerized tomography (CT) scan of the abdomen and pelvis ( Figure 1 ) revealed a diffusely dilated small bowel filled with fecal matter and marked colonic distention with cecal dilatation measuring 9 cm. She was kept nil per os, except for medications, and a nasogastric tube was placed for bowel decompression. A colonoscopy found only granular and punctate erythematous mucosa in the rectum and sigmoid colon with mild nonspecific ileitis and successfully decompressed the dilated colon. A few days after decompression, she developed several watery bowel movements and continued to have abdominal pain. Rapid stool studies were obtained and returned positive for Clostridium difficile antigen and toxin A&B. She was treated with oral vancomycin for 10 days. A repeat CT scan of her abdomen ( Figure 2 ) noted no further small bowel dilation, free air, or free fluid. CT enterography showed no bowel wall thickening or imaging features to suggest inflammatory bowel disease. Her appetite improved, but her abdominal pain persisted despite the antibiotic course, and pain remained out of proportion to her physical examination. The differential was broadened to include AIP. A random urine PBG was elevated at 99.9 mg/g (normal < 0.22 mg/g), with a urine delta aminolevulinic acid (ALA) elevated at 71.9 mg/g (normal < 5.4 mg/g). The fractionation of porphyrins in plasma ( Table 1 ) and urine ( Table 2 ) was suggestive of a biochemical diagnosis of AIP. Intravenous (IV) hematin 1 mg/kg/d and IV dextrose were given for 3 days. After hematin/dextrose therapy, her abdominal pain and bowel symptoms resolved. On subsequent questioning, it was found that she had no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures within our medical institution. She improved clinically and was later discharged with education on how to reduce AIP acute attacks and followed as an outpatient by hematology. Two weeks after discharge, the patient was seen by her primary care physician and noted significant improvements in her appetite and abdominal pain without recurrence of constipation or diarrhea.'}", "questions": ["Which specific laboratory test results in the case document confirm a biochemical diagnosis of acute intermittent porphyria?", "What pattern of plasma and urine porphyrin fractionation is described as supporting acute intermittent porphyria?"], "ground_truth_arguments": ["biochemical diagnosis of AIP ."]}
{"id": "CaseReportBench:train-188", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'XY2 is a boy of seven years of age with X-linked hypophosphatemia. He inherited this genetic disorder from his mother, who in turn inherited it from her father. Mutations in the PHEX gene to Xp22.1 are responsible for the clinical impression of X-linked hypophosphatemia. A molecular analysis of the PHEX gene and sequence analysis showed a hemizygote 1735 G>A(G579R) missense mutation in exon 17 of the PHEX gene in all subjects. XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth. XY2 is intellectually gifted (WISC-III Full Scale IQ: 135, Verbal IQ: 136, Performance IQ: 133) Psychiatric examination demonstrated a DSM-IV-diagnosis of AD, confirmed by the ADI-R (autism diagnostic interview - revised) of the parents and the ADOS-G (autism diagnostic observation schedule). XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X-linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI-R was conducted with the parents and an ADOS-G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC-III test. XY1 is of normal intelligence (total IQ: 107, verbal IQ: 106, performance IQ: 107). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism'}", "questions": ["What is the age of the boy (XY2) at the time of presentation?"], "ground_truth_arguments": ["seven years of age"]}
{"id": "CaseReportBench:train-129", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}", "questions": ["What demographic information and setting of the initial presentation are described for the patient?", "When did the patient's symptoms begin, and what were the nature and typical frequency of the early symptoms?", "What prior medical consultations did she have before admission, and were any diagnoses established?", "What is her past obstetric history and are there any other notable personal or family medical histories?", "What type of genetic testing was conducted on the patient's children, and what were the overall results concerning the disease‑related gene?"], "ground_truth_arguments": ["A 37 - year - old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital ( May 2019 ). Her symptoms had started 4 months previously ( January 2019 ). The initial symptoms included recurring abdominal pain and bloating ( almost once per month ). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis", "She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease", "Targeted mutation analysis was then performed in her two children, but neither of them carried the disease - causing gene"]}
{"id": "CaseReportBench:train-333", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'2. Case presentation:': 'A 13-year-old girl with no history of medical or familial diseases presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache, which had started 10 days ago. Within the next few days following admission, the patient developed an attack of generalized tonic-clonic seizure associated with low-grade fever. On examination, the patient was confused in post ictal state. Otherwise, the neurological and general examination was unremarkable. Patient was hemodynamically stable. Urgent brain computed tomography (CT) scan showed brain edema ( figure 1 ). Cerebrospinal fluid (CSF) analysis, routine blood chemistry tests, blood culture, and serum electrolyte evaluation were performed. On a clinical basis, central nervous system infection was suspected and the patient started to receive acyclovir. Due to severe abdominal pain, abdominopelvic CT scan with contrast was done, which revealed marked distention of large bowel, and no definite air-fluid level or obstructing masses ( figure 1 ). The initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level: 108 milliequivalents per liter (mEq/L), potassium level: 2.7 mEq/L, total calcium level: 4.9 mg/dl, ionized calcium level: 3.5 mg/dl, magnesium level: 0.7 mEq/L, and phosphorus level: 2.1 mEq/L ( table 1 ). Within the next few days, the patient began to become agitated and developed generalized muscle pain despite proper correction of resistant hyponatremia with hypertonic saline 3%. In addition, the patient started to develop polyuria, and polydipsia, despite the normovolemic state, confirmed by clinical examination and central venous pressure monitoring. High suspicion to Bartter-like syndrome was raised as the renal tubular defect with increased renal loss of electrolyte was confirmed by the following laboratory investigation: urine osmolarity 277mOml/kg, serum osmolality 252 mmol/kg, serum chloride 73 mEq/L, and urinary Calcium/creatinine ratio 1.053 ( table 1 ). Within the next few days, she developed weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic. The rest of the examination was normal. Our opinion about the case changed and we had a rising concern about genetic disease. At that time, the whole-exome sequencing was sent abroad to CENTOGENE GmbH (Rostock, Germany) for genetic analysis. Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy (prolonged first time (F) wave latencies with reduced amplitude of compound motor action potentials). Unfortunately, the condition worsened till the patient became intubated and mechanically ventilated due to respiratory muscle involvement. The CSF examination showed cytoalbuminous dissociation, and this made the diagnosis more in favor of Guillain-Barre Syndrome (GBS). The patient received intravenous immunoglobulin (IV IG) (2gm per Kg divided over 5 days) with partial improvement. Due to the failure of multiple trials for weaning from mechanical ventilation, tracheostomy was performed. Genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase (HMBS) gene, which confirmed the diagnosis of autosomal dominant AIP ( figure 2 ). The patient received dextrose 25% and 2 doses of hemin 250 mg once daily for four days, 2 weeks apart followed by another dose after 2 months. There was a marked improvement regarding the weakness, and abdominal pain, and we managed to wean her from mechanical ventilation.'}", "questions": ["What type of genetic finding was reported in the patient, and what category of disorder does it suggest?", "Which gene was identified with a pathogenic variant, and what general diagnosis is associated with such a finding?", "What evidence was used to confirm the final diagnosis in this case?", "What specific genetic test result led to the confirmation of the final diagnosis?"], "ground_truth_arguments": ["confirmed the diagnosis of autosomal dominant AIP"]}
{"id": "CaseReportBench:train-452", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}", "questions": ["What category of disease is being addressed in the case report?"], "ground_truth_arguments": ["CTX", "CTX"]}
{"id": "CaseReportBench:train-539", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["How are the gastrointestinal symptoms of the second infant described in the case report?"], "ground_truth_arguments": ["vomiting and diarrhea"]}
{"id": "CaseReportBench:train-464", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': 'A 37-year-old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous (IV) drug abuser that required a permanent indwelling venous catheter for his repeated attacks; so, he had a port since 9 months ago and received pethidine via that port during the attacks. On admission, a chest computed tomography revealed multiple cavities in both lungs. A large mobile veg on anterior leaflet of tricuspid valve commissure (TVC) with severe TR was also demonstrated in his transthoracic echocardiography. After starting antibiotic therapy and removing the port, the patient underwent TV replacement. In the day of surgery, prior to induction, all standard monitorings were applied; radial artery line and subclavian central venous (CV) line was also indwelled after induction. Premedication was consisted of incremental doses of fentanyl and midazolam. We used propofol and atracurium for induction. Maintenance of anesthesia was done by propofol, atracurium, midazolam and fentanyl. Following sternotomy and heparinization, cardiopulmonary bypass (CPB) was initiated. The patient cooled to 32–34°C. Myocardial protection was provided by hypothermic antegrade blood cardioplegic. The TV was replaced. After 70 min of CPB, separation from CPB was achieved, and heparin was reversed by protamine. Rewarming and weaning from CPB was uneventful. Four units of packed cell were given during CPB; Hct was maintained about 30%. Postoperatively, in Intensive Care Unit (ICU), the patient was extubated in 6 h. We started parenteral carbohydrate as dextrose 50% to prevent AIP attack, and the patient was encouraged to become per oral (PO) as soon as possible. Finally, he was discharged from ICU on day 2 after surgery. AB therapy was continued for several weeks. By providing adequate IV crystalloid fluids, we had prevented any dehydration. The patient was cautiously observed for any symptoms of AIP attack. Throughout his stay in ICU, he had no symptoms such as abdominal pain, dark urine, and neurologic deficit.'}", "questions": ["What weight-related symptoms did the patient present with upon admission?", "Which abdominal symptoms did the patient experience before surgery and during the postoperative period?", "During the ICU stay, which gastrointestinal symptoms were reported as absent?"], "ground_truth_arguments": ["weight loss,", "abdominal pain", "no symptoms such as abdominal pain"]}
{"id": "CaseReportBench:train-203", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Diagnoses:': 'Ultimately, the patient was diagnosed with argininemia with homozygous mutation (c.32T>C) of the ARG1 gene at 10 years old. Blood tests showed mildly elevated blood ammonia and creatine kinase, and persistently elevated bilirubin.', 'Case report': \"The patient was born at 36 +4 weeks’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness. At this time, his height and weight were 86 cm and 12.5 kg, respectively (both were below the 3rd percentile, according to China's 1995 urban 0–18 year-old male height percentiles scale). A neurologic examination focusing on the motor and sensory nervous system and cerebellar function produced unremarkable findings. Laboratory tests revealed retardation of bone age (equivalent to a 1 year old) and mildly elevated total bilirubin (29.4 μmol/L, normal range: 2–24 μmol/L), direct bilirubin (10.4 μmol/L, normal range: 0–7 μmol/L), and indirect bilirubin levels (18.6 μmol/L, normal range: 1.7–17 μmol/L) but normal hepatic enzyme levels. Blood glucose was slightly lower than normal (3.52 mmol/L, normal range: 3.9–6), whereas his electrolytes were normal. Screening tests for hepatitis B and A were negative. A growth hormone excitement test revealed low levels of growth hormone (0 minute: 0.76 ng/mL; 30 minutes: 4.5 ng/mL; 60 minutes: 6.3 ng/mL; 90 minutes: 4.1 ng/mL; and 120 minutes: 1.5 ng/mL). An MRI revealed a normal pituitary gland, and thyroid function was normal. The boy was diagnosed with PGHD and managed accordingly, being treated with growth hormone for about 1 month. No treatment effect was evident. However, he received no follow-up until 10 years of age. At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance. At this time, his height and weight were still below the 3rd percentile, at 116 cm and 20.1 kg, respectively. He exhibited no organomegaly. His muscle strength of the low extremities was grade 4 (Oxford Scale), and he showed increased distal muscle tone than normal, hyper-reflexia, and a negative Babinski sign. Laboratory tests revealed mildly elevated hepatic enzyme levels, including aspartate transaminase (50.9 IU/L, normal range: 0–50 IU/L) and alanine transaminase (52 IU/L, normal range: 0–45 IU/L), as well as mildly elevated total bilirubin (47.7 μmol/L, normal range: 0–25 μmol/L), direct bilirubin (16.4 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (31.3 μmol/L, normal range: 0–25 μmol/L). His creatine kinase (564.4 IU/L, normal range: 55–190 IU/L) and blood ammonia levels (62.3 mmol/L, normal range: 9–30 mmol/L) were slightly elevated. A urine occult blood test was positive (++). Red blood cells (3–4/HP, normal range: 0–3/HP) were evident in a urine sediment microscopy. Both renal ultrasound and renal function were normal, as were the results of cranial MRI and electroencephalography. A peripheral nerve examination revealed reduced compound muscle action potential (CMAP) of the right peroneal nerve and bilateral tibial nerve, while the right peroneal nerve distal latency was suspected to be prolonged. A muscle biopsy revealed neurogenic lesion (Fig. 1 ). A gene test was performed and the results demonstrated that he carried compound homozygote mutations of ARG1 (c.32T > C) (Fig. 2 ). Lee et al and Wu et al reported the mutation, which can lead to argininemia, in South Korea and Chinese populations in 2011 and 2015. Subsequently, his blood and urine amino acid levels were analyzed, revealing a blood arginine concentration of 108.42 μM (normal range: 10–50 μM) as well as elevated urinary excretion of orotic acid; however, his blood citrulline, glutamine, glutamate, and alanine concentrations were normal. His intelligence quotient was lower than normal, at 80. The boy subsequently diagnosed with argininemia. Following the diagnosis, we recommended that the patient begins a low-protein diet (0.8 g/kg/day) to decrease his blood arginine levels, as well as start taking citrulline (150–200 mg/kg/day). His mental state and vomiting had clearly improved after 3 months of this treatment. Laboratory tests conducted again at a local hospital which the following values were obtained (note that the normal ranges used at this hospital slightly differ from those used at our hospital): aspartate transaminase (45 IU/L, normal range: 0–37 IU/L), alanine transaminase (46.1 IU/L, normal range: 0–40 IU/L), total bilirubin (31.9 μmol/L, normal range: 3.4–20.5 μmol/L), direct bilirubin (14.3 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (17.6 μmol/L, normal range: 0–18 μmol/L). His urine occult blood test was positive (+). No red blood cells were evident in his urine sediment microscopy. After 9 months treatment, his height and weight reached 121 cm and 22 kg, but his spastic diplegia symptoms had not improved.\", 'Patient concerns:': 'A Chinese boy initially presented with severe stunting and partial growth hormone deficiency (PGHD) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later (at 10 years old), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy.'}", "questions": ["What low‑protein diet was recommended after the argininemia diagnosis?", "What supplement was advised following the diagnosis?", "What therapeutic goal was stated for the low‑protein diet in the treatment plan?"], "ground_truth_arguments": ["Following the diagnosis , we recommended that the patient begins a low - protein diet ( 0.8 g / kg / day ) to decrease his blood arginine levels , as well as start taking citrulline ( 150–200 mg / kg / day ) ."]}
{"id": "CaseReportBench:train-538", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': \"A 13-year-old male child born off a consanguineous marriage presented with complaints of red colored urine since birth, reddish brown-pigmented teeth, and excessive facial hair since 6 months of age. He also had a burning sensation and recurrent blistering over the sun-exposed areas, which healed with scarring and disfigurement of nails since 1-year of age. His birth and mental developmental history were normal. He had an asymptomatic female sibling 8 years of age, and there was no family history of similar complaints. Examination revealed a short statured male child of height 133 cm (< −3 standard deviations). Abdominal examination revealed a protuberant abdomen with hepatosplenomegaly and undescended testis on the left side. He had obvious hypertrichosis over face involving the cheek and forehead, the forearms and multiple bullae over the dorsum of hands, fingers, forearms, and feet with postinflammatory hyperpigmentation and scars over affected skin. Teeth showed brownish-red pigmentation, fluorescent under Wood's lamp. Nails were discolored. Investigations revealed anemia an Hb of 8.3 g/dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis. Urine was port wine color, which fluoresced in Wood's lamp. Porphobilinogen was not detected on Watson–Schwartz test in the urine. Ultrasonography of abdomen confirmed the hepatomegaly, splenomegaly, and the undescended testes with hydrocele on the right side. Mutation analysis was carried out for the affected child and his parents. The affected child exhibited a missense mutation in the UROS gene identified as a transversion of A to G at nucleotide 56, resulting in a substitution of tyrosine by cysteine. The patient showed a homozygous mutant profile, and the parents were heterozygous carriers for the mutation. Based on the clinical presentation with onset in early childhood of a photosensitive disorder with erythrodontia, hypertrichosis, fluorescent red urine, absence of porphobilinogen in urine, and a demonstrated mutation of the UROS gene the child was diagnosed as a case of CEP. He was managed with sun avoidance and liberal use of sunscreen administration. He was referred to the surgical center for definitive management of undescended testis. He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens (HLA) matched donor.\"}", "questions": ["What was the patient's mental developmental history?"], "ground_truth_arguments": ["mental developmental history were normal"]}
{"id": "CaseReportBench:train-524", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case 2': 'An 18-year-old girl was admitted to our hospital following development of generalized tonic-clonic seizure in November 2016. Ten days ago, she was diagnosed with ileus because of abdominal pain as well as constipation in her local hospital. However, the symptoms were not relieved and a series of tests including abdominal X-ray, CT scan, and ultrasound were normal. Her brain MRI was performed in her local hospital indicating PRES (Fig. 3 ). MR angiography showed no abnormality (data not shown). However, the diagnosis was vague and the patient was transferred to the emergency department of our hospital due to seizures. Anticonvulsants including benzodiazepines and oxcarbazepine were used to control the seizures. The recurrent abdominal pain and seizures gave us reason to suspect of AIP, given the prognosis from case 1. She had no family history of similar symptomatology or other particularly notable medical history. At the time of admission, her blood pressure was 136/101 mm Hg, and her heart rate was 109/min. The general physical examination was normal and there was no focal neurological deficit. On the night of admission, the patient had hallucination. Except for remarkable hyponatremia of 104 mmol/L, her serum potassium was 3.0 mmol/L, aspartate transaminase 243 U/L, alanine transaminase 142 U/L, and total bilirubin 37 μmol/L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero-negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid (CSF) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution (Fig. 4 ). AIP was confirmed by 3 repeated urine Watson–Schwartz tests. The patient was given a high carbohydrate diet and intravenous dextrose. No hematin was available for her, but her status improved gradually when she was discharged. No seizures occurred, and her abdominal pain regressed. Two weeks later, a repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions (Fig. 5 ). One month later, she recovered completely and went back to work. No acute attacks have occurred to date. Because this was cases report without any research involving human beings or experimental subjects, the ethical approval was not required in our institute. But patients have provided informed consent for publication of the case.', 'Case presentation:': \"Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson–Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up.\", 'Case 1': 'In December 2014, a 27-year-old man was admitted to our hospital for abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week. He was diagnosed with acute pancreatitis with mild elevated urine amylase in his local hospital. No abnormalities were found in his abdominal computed tomography (CT) and X-ray. However, the paroxysmal pain was not relieved, and his blood pressure increased. Six days later, a generalized tonic-clonic seizure occurred. Then, partial seizures in the left limb continued. He was transferred to our hospital. No particular medical or family history was reported. At the time of admission, he described recurrent severe paroxysmal abdominal and lumbar pain. His clinical examination was unremarkable, except for decreased tendon reflex in the 4 limbs. There was no complaint of visual disturbance. The patient had moderately increased blood pressure (159/101 mm Hg) and tachycardia (112/min). His creatine kinase was 246 U/L (normal, 0–170 U/L), aspartate transaminase was 42 U/L (15–40 U/L) and serum sodium was 130 mmol/L (normal, 137–147 mmol/L). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1-weighted images and were hyperintense on T2-weighted and fluid-attenuated inversion recovery images. Diffusion-weighted images (DWI) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient (ADC) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES (Fig. 1 ). There was mild contrast enhancement (data not shown). Electroencephalography showed diffuse slow waves without epileptiform discharges. The results of the cerebrospinal fluid analysis were normal. His severe recurrent abdominal pain without clear etiology was suspect of AIP. The diagnosis of AIP was made after 3 repeated positive urine Watson–Schwartz tests for porphobilinogen (PBG). His urine turned dark and red upon exposure to light (Fig. 2 ). Glucose infusion and a high carbohydrate diet were given to the patient, as hematin was not available in our hospital. The patient responded well and recovered gradually. He was discharged with no seizure or abdominal pain. Upon review, he remained asymptomatic.'}", "questions": ["Which abdominal imaging modalities (X‑ray, CT, ultrasound) were performed for the patients and what were their findings?", "What electrolyte and liver function abnormalities were reported in the female patient, including sodium, potassium, AST, ALT, and bilirubin levels?", "What serologic tests for autoimmune antibodies and viral infections were conducted in the female patient and what were the results?", "What heavy metal screening tests were performed in the female patient and what were the outcomes?", "What were the cerebrospinal fluid analysis results for the female patient?", "What changes were observed on the brain MRI performed six days after admission in the female patient?", "How many urine Watson–Schwartz tests were performed for each patient and what were the results, including any description of urine color change?", "What brain MRI findings indicated posterior reversible encephalopathy syndrome (PRES) in the patients?", "What laboratory values (creatine kinase, AST, serum sodium) and other biochemical test results were reported for the male patient, and were any additional tests (connective tissue, viral, heavy metal, thyroid, antithyroid antibodies) abnormal?", "Describe the MRI signal characteristics of the brain lesions in the male patient (T1, T2, FLAIR, DWI, ADC, contrast enhancement)."], "ground_truth_arguments": ["and a series of tests including abdominal X - ray, CT scan, and ultrasound were normal", "Except for remarkable hyponatremia of 104 mmol / L, her serum potassium was 3.0 mmol / L, aspartate transaminase 243 U / L, alanine transaminase 142 U / L, and total bilirubin 37 μmol / L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero - negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid ( CSF ) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution", "3 repeated urine Watson – Schwartz tests", "PRES on brain magnetic resonance imaging ( MRI ).", "diagnosis was made after repeated Watson – Schwartz tests.", "No abnormalities were found in his abdominal computed tomography ( CT ) and X - ray.", "His creatine kinase was 246 U / L ( normal, 0–170 U / L ), aspartate transaminase was 42 U / L ( 15–40 U / L ) and serum sodium was 130 mmol / L ( normal, 137–147 mmol / L ). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1 - weighted images and were hyperintense on T2 - weighted and fluid - attenuated inversion recovery images. Diffusion - weighted images ( DWI ) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient ( ADC ) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES ( Fig. 1 ). There was mild contrast enhancement", "The results of the cerebrospinal fluid analysis were normal.", "3 repeated positive urine Watson – Schwartz tests for porphobilinogen ( PBG ). His urine turned dark and red upon exposure to light"]}
{"id": "CaseReportBench:train-140", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case report': 'In 1989, a 21-year-old male experienced visual loss after diving from a diving board. Ocular examination was performed the same day, and revealed bilateral subretinal hemorrhages and angioid streaks. After clearing of the hemorrhages, more breaks of Bruch’s membrane were identified. The macula was not affected and vision returned to normal in both eyes. Twenty years later, in April 2009, he presented again because of recent visual loss in the left eye. Visual acuity (VA) was 20/25 in the right eye (RE) and 20/40 in the left eye (LE). Clinical examination, FA, and OCT revealed active choroidal neovascularisation nasal to the fovea with leakage and edema. One month after a first intravitreal injection of bevacizumab, the edema had resolved and vision improved. Close follow-up with consideration of additional anti-VEGF injections was adviced. Moreover, we observed in both eyes angioid streaks, peau d’orange and a few comet tails, and made a tentative diagnosis of PXE. We identified the sequellae of diving induced breaks of Bruchs’ membrane with linear vertical break formation, different from the irregular course and spiderweb configuration of the angioid streaks. During the following months a total of 8 injections of bevacizumab were administred on the LE and despite this treatment growth of the choroidal neovascularization (CNV) was observed with further deterioration of vision. In January 2010, active CNV was also identified in the right eye and treatment with bevacizumab intravitreal injections was initiated. At last examination, in April 2011, VA was 20/60 in the right eye and 20/250 in the left eye, with in the left eye a large subfoveal CNV expanding on both sides of the fovea, and in the RE a smaller and mildly active subfoveal CNV requiring further treatment (Figure 1 (Fig. 1), Figure 2 (Fig. 2), Figure 3 (Fig. 3), Figure 4 (Fig. 4), Figure 5 (Fig. 5), Figure 6 (Fig. 6), Figure 7 (Fig. 7), Figure 8 (Fig. 8), Figure 9 (Fig. 9), Figure 10 (Fig. 10) ). With the aim to confirm PXE, the patient was referred for dermatologic examination and biopsy. At age 43, there were no typical plucked-chicken appearance, no papules, macules or other skin lesions. Three biopsies from the flexural skin of the axilla and the neck did not reveal PXE related changes. Subsequently, to further exclude or confirm PXE, a blood sample for genetic analysis was taken. Analysis showed that our patient was homozygous for the R1141X-mutation in the ABCC6-gene. The diagnosis of PXE was withheld, discussed with the patient, and shared with his treating generalist to allow optimal further follow-up of the condition.'}", "questions": ["Provide a concise summary of the dermatologic examination, noting any skin lesions (or lack thereof) and the histopathologic findings from the skin biopsies."], "ground_truth_arguments": ["no typical plucked - chicken appearance, no papules, macules or other skin lesions. Three biopsies from the flexural skin of the axilla and the neck did not reveal PXE related changes"]}
{"id": "CaseReportBench:train-108", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'We report on a 5-year-old girl with a history of pink-stained urine as a newborn. Disease onset occurred in the tenth month of life. Her deciduous teeth sprouted with a red-brown color. She also suffered from episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation (fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas. Spleen enlargement was also observed. Urine porphyrins were extremely elevated to 16 μmol/dl with a predominance of coproporphyrins and uroporphyrins. However, the detailed concentration of each porphyrin was not analyzed. Severe cutaneous photosensitivity, blistering of light-exposed skin, history of pink-stained diapers and accumulation of porphyrins in the blood and various other tissues, particularly erythrodontia (fig. 1b ), suggested the diagnosis of CEP. The clinical and biochemical data of the patient are summarized in table 1 . With strict avoidance of UV and visible light, use of topical sunscreen, oral treatment with β-carotene and antibiotic for preventing bacterial infection of the skin, the bullae healed, leaving milia and hyperpigmented scars without the need of a blood transfusion. Mutation analysis of the UROS gene of the patient with CEP was performed. The DNA of exons 2–10 including splicing junctions of all exons was amplified by PCR and then sequenced. A single missense mutation corresponding to a G-to-T transversion (11,776 g>t) in exon 2 was found, leading to an amino acid change from valine at position 3 to phenylalanine (fig. 2 ). The result indicated that the patient was homozygous for this mutation. Then, we also analyzed the UROS genes of her parents who were shown to be heterozygote carriers of this mutation (fig. 3 ). Her brother had died of a disease similar to hers in terms of symptoms and abnormalities, suggesting that he had the same gene mutation (V3F). Conversely, on the basis of the pedigree analysis spanning three generations, no other symptomatic patients were found. To confirm the genotype-phenotype relationship, we constructed a pET-duet vector carrying mutated cDNA of UROS and transformed it into an Escherichia coli BL21 strain. The expression of UROS in bacteria was induced at 25°C. After purification of the expressed enzyme with nickel ion-beads (Qiagen Inc., Valencia, Calif., USA), the activity of mutated UROS (V3F) was compared with that of normal enzyme by the method of Wright and Lim. The specific activity of the mutated UROS was less than 16.1% that of the control.'}", "questions": ["At what age did the disease first manifest in the patient?"], "ground_truth_arguments": ["Disease onset occurred in the tenth month of life"]}
{"id": "CaseReportBench:train-27", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case Report': 'A 29-year-old male patient presented with a 6-year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk. He complained of skin tightness around the abdomen while walking. He wandered to and fro between different specialists but without much help. He was diagnosed as Type 1 diabetic 6 years back and was receiving insulin since then. Cutaneous examination revealed large ill-defined hyperpigmented indurated plaques extending symmetrically from mid-truncal area to both thighs characteristically sparing the knees and medial aspect of buttocks. A prominent constriction band was noted around the abdomen. The lesions over thighs were associated with hypertrichosis and were warm to touch. Examination also revealed short stature (145 cm), hypospadias, micropenis, scrotal swelling, and mild hepatomegaly and inguinal lymphadenopathy. Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal. Nails and teeth were normal. Ophthalmologic and auditory examinations were normal. On the basis of cutaneous findings, we kept differential diagnosis of morphea profunda, pseudoscleroderma, POEMS syndrome, Rosai–Dorfman syndrome, pigmented hypertrichotic dermatosis, and scleredema as the possibilities. A deep skin biopsy was done from the indurated plaque on the lateral part of the left thigh and sent for histopathology. Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes. Routine laboratory investigations revealed a fasting blood glucose level of 250 mg/dL and random blood sugar of 338 mg/dL with glycated hemoglobin 10.2%. Thyroid profile, liver function, kidney function, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibody was negative. Ultrasound abdomen revealed mild hepatosplenomegaly and abdominal lymphadenopathy. Color Doppler study of the scrotal region revealed small penis, normal echotexture, no calcific plaques, and small left testis. Chest radiography and nerve conduction studies were normal. Computed tomography (CT) demonstrated marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees. Para-aortic and inguinal lymphadenopathy and mild pericardial effusion were noted. Marked thickening of the scrotum was seen. A diagnosis of “H syndrome” was made. Genetic testing was not possible due to resource constraints.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.'}", "questions": ["What type of diabetes does the patient have and how long has it been diagnosed?", "Describe the condition of the patient's axillary, pubic, and facial hair and any noted voice characteristics.", "How does the patient's glycemic profile (fasting glucose, random glucose, and HbA1c) compare to normal reference ranges?", "Are the patient's serum testosterone, follicle‑stimulating hormone, and luteinizing hormone levels reported as normal or abnormal?"], "ground_truth_arguments": ["as Type 1 diabetic", "Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal", "fasting blood glucose level of 250 mg / dL and random blood sugar of 338 mg / dL with glycated hemoglobin 10.2 %", "serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal"]}
{"id": "CaseReportBench:train-172", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'A 13-year-old boy born out of a consanguineous marriage presented to the outpatient department with hyperpigmentation and hypertrichosis of lower extremities and trunk for last 4 years. The patient also had hearing loss for more than 5 years which was progressive and was using hearing aid for the same. There was no family history of similar skin changes. On mucocutaneous examination well defined, bilaterally symmetrical hyperpigmented, indurated plaques with marked hypertrichosis were present over medial aspect of thighs and legs. Knees and feet were spared. Similar lesions were present over sacral area and lower back bilaterally. General physical examinations showed mild hepatomegaly and pallor. He had short stature for his age (131 vs. 154 cm). Hallux valgus was also present. Routine laboratory investigations revealed haemoglobin to be 6.7 g/dl. Liver function tests, thyroid profile, serum cortisol (15.25 μg/dL), and blood sugar were normal. Chest X-ray was normal. Antinuclear antibody was negative. Growth hormone level was reduced to 0.77 ng/ml (normal range 1–14.4 ng/ml). Serum Vitamin D3 level (51.88 vs. 81–250 nmol/L) was found to be low. No “M” spike was seen in serum protein electrophoresis. Ultrasonography (USG) abdomen revealed mild hepatomegaly. USG of scrotum was normal. Contrast enhanced computed tomography head, and orbit revealed bilateral mild axial proptosis. Skin biopsy was taken from the hyperpigmented plaque on the thigh and revealed mild irregular acanthosis, and increased melanin deposition in basal keratinocytes. Significant thickening of collagen bundles in upper and mid-dermis was seen along with perivascular infiltrate of histiocytes. Immunohistochemistry was positive for CD68 and CD45 in dermal perivascular histiocytic infiltrate and for CD34+ in vessel endothelium. The final diagnosis of H syndrome was made based on the characteristic clinical and histopathological findings.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient had given his consent for his images and other clinical information to be reported in the journal. The patient understood that his name and initial would not be published and due efforts would be given to conceal his identity, but anonymity could not be guaranteed.'}", "questions": ["What is the patient's measured height and the expected normal height for his age?", "What is the patient's hemoglobin concentration reported in the laboratory findings?"], "ground_truth_arguments": ["short stature for his age ( 131 vs. 154 cm )", "haemoglobin to be 6.7 g / dl."]}
{"id": "CaseReportBench:train-247", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}", "questions": ["At what age or age range did the patient first experience symptoms such as muscle stiffness, calf cramps, urinary frequency, or spastic paraparesis?"], "ground_truth_arguments": ["her twenties", "her twenties"]}
{"id": "CaseReportBench:train-495", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}", "questions": ["At what age did the patient first present with symptoms?"], "ground_truth_arguments": ["15‐day‐old"]}
{"id": "CaseReportBench:train-72", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as \"disease causing\" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most \"likely damaging\" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}", "questions": ["At what age did the proband first present with symptoms (e.g., acute viral fever and laboratory abnormalities)?", "What was the age of the proband’s sister when she was screened and diagnosed?"], "ground_truth_arguments": ["4 years of age ,", "3 - year - old"]}
{"id": "CaseReportBench:train-242", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Report': 'A 52-year-old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene. Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme. We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme. After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What systemic medical conditions or comorbidities are reported for the patient in the case description?"], "ground_truth_arguments": ["hypertension"]}
{"id": "CaseReportBench:train-481", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case 2': \"The second case was of a 28-year-old male who was born of a non-consanguineous marriage, had delayed psychomotor milestones with mental retardation, congenital cataract, and recurrent episodes of diarrhea since early childhood. He had history of progressive spastic diplegia, tremulousness in both upper limbs and scanning speech. The patient had impaired attention, vigilance, comprehension, and new learning ability. Pan-sensory impairment was noted below knee with impaired limb coordination in upper limbs. Patient's skin biopsy of swelling over Achilles confirmed xanthoma. MRI brain showed altered signals in bilateral cerebral peduncles, ventral pons, both the middle cerebellar peduncles and medullary pyramids. Based on the clinical, radiological, and biopsy findings of the Achilles tendon swelling, diagnosis of CTX was confirmed.\", 'Case 1': 'A 50-year-old commerce graduate with degree in law presented to us with insidious onset gradually progressive spastic diplegia for 20 years followed later by gradually progressive bladder dysfunction, poor scholastic performance, and a single seizure. He was born to non-consanguineous parents and had unremarkable early psychomotor development. Pedigree analysis revealed absence of any family history in previous two generations. On examination, patient had thoracic kyphosis with contractures at hip, knee, and ankle joints. He had firm, non-tender swellings over ankles, patella, and elbows bilaterally. Detailed higher mental function assessment revealed impairment of attention, new learning and visual memory with normal language functions. His speech was slow and slurred but could be comprehended with little difficulty. All cranial nerve functions were intact. The patient had severe spasticity in both lower limbs with brisk deep tendon reflexes in both the upper and the lower limbs, extensor plantar responses, and normal sensory examination. Blood investigations revealed a normal complete hemogram (including hemoglobin, total leukocyte count, differential leukocyte count), liver and kidney function tests, serum electrolytes and, triglyceride and cholesterol levels. X-rays of ankle, knee, and elbow showed homogenous soft tissue swelling. MRI brain showed T2-weighted hyperintensities in dentate nucleus regions bilaterally and generalized cerebral and cerebellar atrophy. Plasma cholestanol levels were found to be raised suggesting cerebrotendinous xanthomatosis. The genetic analysis of CYP27A1 gene of the patient was carried out by the method of Polymerase Chain Reaction and sequencing of both the DNA strands was done. The analysis revealed heterozygous mutation in exon 6 with substitution of cytosine by thymine at 1151 position (c. 1151C > Tp.P384L) and a novel mutation in exon 1 of CYP 27 gene with substitution of thymine by cytosine at nucleotide position 2 of the gene (c. 2T > Cp.M1T). The mutation in exon 6 is already described as disease causing while the mutation in exon 1 is previously unreported as per the current Human Gene Mutation Database. The mutation causes loss of a highly conserved start codon and likely results in loss of functional protein. The patient is receiving atorvastatin besides physical therapy and chenodeoxycholic acid (CDCA) is being arranged as it is not marketed in India.'}", "questions": ["What congenital eye abnormalities are described in the patients' histories?"], "ground_truth_arguments": ["congenital cataract,"]}
{"id": "CaseReportBench:train-222", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'2. Case presentation:': 'A 13-year-old girl with no history of medical or familial diseases presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache, which had started 10 days ago. Within the next few days following admission, the patient developed an attack of generalized tonic-clonic seizure associated with low-grade fever. On examination, the patient was confused in post ictal state. Otherwise, the neurological and general examination was unremarkable. Patient was hemodynamically stable. Urgent brain computed tomography (CT) scan showed brain edema ( figure 1 ). Cerebrospinal fluid (CSF) analysis, routine blood chemistry tests, blood culture, and serum electrolyte evaluation were performed. On a clinical basis, central nervous system infection was suspected and the patient started to receive acyclovir. Due to severe abdominal pain, abdominopelvic CT scan with contrast was done, which revealed marked distention of large bowel, and no definite air-fluid level or obstructing masses ( figure 1 ). The initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level: 108 milliequivalents per liter (mEq/L), potassium level: 2.7 mEq/L, total calcium level: 4.9 mg/dl, ionized calcium level: 3.5 mg/dl, magnesium level: 0.7 mEq/L, and phosphorus level: 2.1 mEq/L ( table 1 ). Within the next few days, the patient began to become agitated and developed generalized muscle pain despite proper correction of resistant hyponatremia with hypertonic saline 3%. In addition, the patient started to develop polyuria, and polydipsia, despite the normovolemic state, confirmed by clinical examination and central venous pressure monitoring. High suspicion to Bartter-like syndrome was raised as the renal tubular defect with increased renal loss of electrolyte was confirmed by the following laboratory investigation: urine osmolarity 277mOml/kg, serum osmolality 252 mmol/kg, serum chloride 73 mEq/L, and urinary Calcium/creatinine ratio 1.053 ( table 1 ). Within the next few days, she developed weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic. The rest of the examination was normal. Our opinion about the case changed and we had a rising concern about genetic disease. At that time, the whole-exome sequencing was sent abroad to CENTOGENE GmbH (Rostock, Germany) for genetic analysis. Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy (prolonged first time (F) wave latencies with reduced amplitude of compound motor action potentials). Unfortunately, the condition worsened till the patient became intubated and mechanically ventilated due to respiratory muscle involvement. The CSF examination showed cytoalbuminous dissociation, and this made the diagnosis more in favor of Guillain-Barre Syndrome (GBS). The patient received intravenous immunoglobulin (IV IG) (2gm per Kg divided over 5 days) with partial improvement. Due to the failure of multiple trials for weaning from mechanical ventilation, tracheostomy was performed. Genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase (HMBS) gene, which confirmed the diagnosis of autosomal dominant AIP ( figure 2 ). The patient received dextrose 25% and 2 doses of hemin 250 mg once daily for four days, 2 weeks apart followed by another dose after 2 months. There was a marked improvement regarding the weakness, and abdominal pain, and we managed to wean her from mechanical ventilation.'}", "questions": ["What is the age of the patient?"], "ground_truth_arguments": ["13 - year - old"]}
{"id": "CaseReportBench:train-62", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["At what age did the patient first develop facial hair or other virilizing signs?"], "ground_truth_arguments": ["8 - year - old ."]}
{"id": "CaseReportBench:train-230", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Patient Consent': 'Patient consent was obtained.', 'Case Presentation': 'A 24-year-old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease (CKD) was referred for preconception counseling. Cystinosis was confirmed by an elevated leucocyte cystine level in infancy. Early diagnosis, made possible by cystinosis in an older sibling, and good treatment adherence contributed to delayed kidney disease progression. Electrolyte abnormalities secondary to Fanconi syndrome were treated with daily supplemental dosages of potassium 96 mmol, phosphate 25.2 mmol, and sodium bicarbonate 53.6 mmol. There were no overt extra-renal complications apart from mild photophobia. Her average prepregnancy urine protein-to-creatinine ratio was 132 mg/mmol, α1-microglobulin-to-creatinine ratio was 30.7 mg/mmol, and estimated glomerular filtration rate (eGFR) was 89 ml per minute per 1.73 m 2 . On confirmation of pregnancy, losartan and cysteamine were discontinued. Low-dose aspirin was initiated for the prevention of pre-eclampsia. As expected, proteinuria and eGFR increased during pregnancy. 8 Blood pressure remained normal with no evidence of gestational hypertension or pre-eclampsia. Daily electrolyte supplementation increased to potassium 128 mmol and phosphate 33.6 mmol, with no increase in the dose of sodium bicarbonate. Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein. The pregnancy was complicated by recurrent urinary tract infections (UTIs) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia. After treatment of the complicated UTI, prophylactic oral antibiotics were administered for the remainder of pregnancy without UTI recurrence. She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes. The infant was admitted to the neonatal intensive care unit for 23 days. Cysteamine was reinitiated immediately after delivery and enalapril was initiated at 2 weeks postpartum. The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1-microglobulin-to-creatinine ratio and eGFR were stable ( Figure 1 ). Figure 1 Urinary proteins and eGFR at baseline, during pregnancy and postpartum. eGFR, estimated glomerular filtration rate. While breastfeeding, her delayed-release cysteamine dosage was 675 mg twice daily (0.84 mg/m 2 /d) compared with her prepregnancy dosage of 825 mg twice daily (1.06 mg/m 2 /d). The cysteamine dosage was reduced during breastfeeding as a precaution because of the lack of lactation safety data. She exclusively breastfed for 4 months and discontinued at 5 months. The cysteamine dosage subsequently stabilized at 750 mg twice daily (0.95 mg/m 2 /d). Breastmilk samples were collected and analyzed ( Table 1 and Supplementary Methods ). The calculated relative infant dose was 0.4%. The predicted infant cysteamine dose over 24 hours was 0.52 mg. Infant cysteamine levels were not measured. The infant had normal growth and development at 18 months and a normal leucocyte cystine level. Table 1 Breastmilk cysteamine concentration relative to dose of delayed-release cysteamine bitartrate at steady state Time postdose (h) Breastmilk cysteamine concentration (mg/l) 0 0.12 2 0.76 4 1.87 6 0.51'}", "questions": ["What was the maternal blood pressure status throughout pregnancy and was there any evidence of gestational hypertension or pre‑eclampsia?", "What urinary tract infection complications occurred during pregnancy, including timing, recurrence, and any associated bacteremia or specific pathogens?", "What obstetric events occurred at 33 weeks and 1 day gestation, and what were the delivery details such as infant weight, mode of delivery, and Apgar scores at 1, 5, and 10 minutes?", "How did proteinuria, α1‑microglobulin‑to‑creatinine ratio, and eGFR change in the postpartum period compared with pre‑pregnancy values?", "For how many months did the mother exclusively breastfeed, and at what point was breastfeeding discontinued?"], "ground_truth_arguments": ["Blood pressure remained normal with no evidence of gestational hypertension or pre - eclampsia", "The pregnancy was complicated by recurrent urinary tract infections ( UTIs ) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia", "She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes", "The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1 - microglobulin - to - creatinine ratio and eGFR were stable", "She exclusively breastfed for 4 months and discontinued at 5 months"]}
{"id": "CaseReportBench:train-573", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'XY2 is a boy of seven years of age with X-linked hypophosphatemia. He inherited this genetic disorder from his mother, who in turn inherited it from her father. Mutations in the PHEX gene to Xp22.1 are responsible for the clinical impression of X-linked hypophosphatemia. A molecular analysis of the PHEX gene and sequence analysis showed a hemizygote 1735 G>A(G579R) missense mutation in exon 17 of the PHEX gene in all subjects. XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth. XY2 is intellectually gifted (WISC-III Full Scale IQ: 135, Verbal IQ: 136, Performance IQ: 133) Psychiatric examination demonstrated a DSM-IV-diagnosis of AD, confirmed by the ADI-R (autism diagnostic interview - revised) of the parents and the ADOS-G (autism diagnostic observation schedule). XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X-linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI-R was conducted with the parents and an ADOS-G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC-III test. XY1 is of normal intelligence (total IQ: 107, verbal IQ: 106, performance IQ: 107). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism'}", "questions": ["What X‑linked metabolic disorder is confirmed as the diagnosis in the patient?"], "ground_truth_arguments": ["X - linked hypophosphatemia"]}
{"id": "CaseReportBench:train-19", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What vestibular or balance-related symptoms did the patient report?", "Describe the patient's hearing impairment, including its laterality, possible cause, and any use of hearing aids.", "What visual disturbances did the patient experience during her illness?"], "ground_truth_arguments": ["dizziness", "bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years", "blurred vision,"]}
{"id": "CaseReportBench:train-488", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': \"A 27-year-old nulliparous woman, a diagnosed case of 21-hydroxylase deficient simple virilizing form of classic CAH visited our department from the endocrinology department for pregnancy maintenance. Her diagnosis had been identified at eleven years old with a high testosterone level, raised 17-hydroxyprogeterone level, enlarged clitoris and normal karyotype (46, XX). At the age of 12, she underwent clitoral resection and vaginoplasty at urology department of our hospital. She took dexamethasone (minimum dose 0.5 mg/day to maximum dose 1.0 mg/day) after operation. Four months later, her breasts expanded and in six months' time, menstruation began. The treatment sustained without any other complication. The treatment had continued and urology department referred this case to endocrinology department when she was 27 years old. Medication was changed to prednisolone and the endocrinology department had prescribed it (minimum dose 10 mg/day to maximum dose 20 mg/day) before pregnancy. She married at 25 years old and had a spontaneous abortion at 26 years old. After the abortion, she got pregnant spontaneously without any trial of assisted reproductive technology. At 12+3 week of gestation, she first visited our department. The first trimester screening conducted at the first visit of 12+3 week of gestation was normal and quad test conducted at 16+3 week of gestation was also normal. She was diagnosed with gestational diabetes mellitus as blood sugar was mildly increased than normal range in the 100 g oral glucose tolerance test conducted at 24+6 week of gestation. Lifestyle modification was recommended to the patient and blood sugar was well-controlled without any medication. Ultrasonography was performed at two to four weeks. The development of fetus was appropriate to the gestational age without any sign of intrauterine growth retardation or large for gestational age. During pregnancy, she continued to take prednisolone (minimum dose 7.5 mg/day to maximum dose 20 mg/day) on demand at endocrinology department. Cesarean section was preferred other than vaginal delivery, as she had cephalopelvic disproportion on examination and history of vaginoplasty. She delivered female weighs 2,990 g by elective cesarean section at 38+4 week of gestation. The baby exhibited normal 7 Apgar score and did not require oxygen or respiratory assistance. The external genitalia was normal and there was a sign of normal karyotype (46, XX) in the result of chromosomal study. After the delivery, the patient had took prednisolone (15 mg/day) consistently for the CAH. After one time of spontaneous abortion, 3 years later, at the age of 30, she became pregnant of the second baby spontaneously. She was diagnosed with gestational diabetes mellitus due to the mildly increased level of blood sugar at the 100 g oral glucose tolerance test conducted at 23+4 week of gestation, however, the blood sugar was well-controlled by life style modification without medication. The development of fetus was appropriate to the gestational age and antenatal care did not show any particular sign. During this pregnancy, she continuously took the prednisolone (minimum dose 7.5 mg/day to maximum dose 15 mg/day) prescribed by endocrinology department. She delivered 3,250 g female baby at 38+2 week of gestation, by cesarean section. The baby exhibited normal Apgar score and did not require oxygen or respiratory assistance. Four years old baby and eleventh month old bay have shown normal external genitalia and normal development up to now.\"}", "questions": ["What type of congenital adrenal hyperplasia has been diagnosed in this patient?"], "ground_truth_arguments": ["a diagnosed case of 21 - hydroxylase deficient simple virilizing form of classic CAH"]}
{"id": "CaseReportBench:train-273", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case History': 'A 32-year-old, mentally retarded female presented with gait instability and right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints. Patient had undergone surgery for cataracts in both eyes 10 years back. On examination patient was found to have ataxia, soft, non-tender swelling along the posterior aspect of both ankle joints, as well as right malar emminence. A preliminary diagnosis of cerebrotendinous xanthomatosis was made and evaluation was started. Lipid profile revealed total cholesterol of 306 mg/dl (LDL 205 mg/dl, VLDL 46mg/dl, HDL 55 mg/dl) and triglycerides of 526 mg/dl. Rest of the blood chemistry was normal. Radiograph of ankle joints revealed soft tissue swellings along the posterior aspect of both ankle joints and calcaneal bones. MRI of ankle joints revealed fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images consistent with tendinous xanthomatosis. MRI brain revealed hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images. Susceptibility weighted images revealed comma shaped hypointense signal of bilateral dentate nuclei. Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma. Serum cholestanol levels were raised (14 1 micromole/liter). With a combined spectrum of clinical, biochemical and radiological findings, a diagnosis of cerebrotendinous xanthomatosis(CTX) was made.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Describe the clinical swellings noted on examination, including their locations and physical characteristics.", "What soft‑tissue abnormalities were identified on radiographs or MRI of the ankle region?", "What MRI signal characteristics were observed in the subcutaneous tissue of the swelling, and what was the result of the FNAC performed on that lesion?"], "ground_truth_arguments": ["right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints", "soft, non - tender swelling along the posterior aspect of both ankle joints, as well as right malar emminence", "tissue swellings along the posterior aspect of both ankle joints and calcaneal bones", "Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma"]}
{"id": "CaseReportBench:train-50", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}", "questions": ["For the male sibling (Case 2), at what age was metreleptin therapy started, what dose (mg/kg/day) was given, and what immediate changes in hyperinsulinemia and hyperlipidemia were reported?", "For the female sibling (Case 1), at what age was metreleptin trial enrollment and treatment begun, what dose (mg/kg/day) was administered, and how soon after initiation were marked metabolic improvements observed?"], "ground_truth_arguments": ["At 11 yr and 6 mo of age , metreleptin was introduced at a dose of 0.04 mg / kg / d , and there was an immediate improvement of hyperinsulinemia and hyperlipidemia", "At 11 yr and 5 mo of age , she was enrolled in a clinical trial of metreleptin . Metreleptin treatment was initiated at a dose of 0.06 mg / kg / d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation"]}
{"id": "CaseReportBench:train-250", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["How were the newborn's external genitalia described at birth?"], "ground_truth_arguments": ["normal female external genitalia"]}
{"id": "CaseReportBench:train-7", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["What is the confirmed diagnosis for the newborns described in the case report?", "Which specific inborn error of metabolism is associated with the homozygous c.772C>T mutation in the StAR gene?", "What disorder was identified in both the first and second child based on clinical, laboratory, and genetic findings?", "How is the condition characterized by adrenal insufficiency and a StAR gene mutation referred to in the document?"], "ground_truth_arguments": ["CLAH"]}
{"id": "CaseReportBench:train-342", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE REPORT': \"In 1986, a previously healthy 18-year-old male presented to our hospital with a 1-week history of fever, headache and vomiting. Meningism, but no focal neurological signs, was noted on examination. Lumbar puncture was performed, revealing slight elevation of protein in the cerebrospinal fluid (CSF) but no increased cell count. Over the next few days, right-sided weakness developed. Electroencephalogram demonstrated left parieto-occipital focal slowing. Results of T1/T2-weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area. The patient was commenced on acyclovir, but herpes serology came back negative. When generalized tonic-clonic seizures ensued, anticonvulsant therapy with carbamazepine was established. The patient was finally discharged with a provisional diagnosis of viral encephalitis, although no causative agent was found. No residual neurological deficits persisted. In 1989, hearing impairment was first documented and ascribed to the previous encephalitis. The following years saw recurrent admissions for seizures, and sodium valproate was added. The patient's functional status deteriorated progressively. In 1999, he was diagnosed with diabetes mellitus, requiring insulin straightaway. The patient's sister was admitted to our department in October 2010 with gross oedema of the legs. Her medical history included diabetes and sensorineural deafness. Advanced renal impairment was noted. In view of her phenotype, we suspected maternally inherited diabetes and deafness (MIDD). The 3243A>G mutation in the MT-TL1 gene of the mitochondrial DNA (mtDNA) was subsequently demonstrated in blood leucocytes, confirming the diagnosis. When her brother was admitted in October 2011 for anorexia, we re-evaluated his past medical notes. In the initial CSF analysis, no lactate levels had been checked. Electrocardiogram showed Wolff–Parkinson–White syndrome. Macular dystrophy, but no signs of diabetic retinopathy, was found on fundoscopy. CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto-occipital hypodensity, likely representing a previous stroke-like event (Fig. 1 ). Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) was deemed a likely explanation for his multi-systemic disease and was confirmed by demonstration of the 3243A>G transition in blood and urine. The heteroplasmy rate (the mixture of normal and mutated mitochondrial DNA) was 50 and 90%, respectively. Anticonvulsant therapy was switched to levetiracetam and treatment with coenzyme Q 10 was started. The patient now lives in a nursing home. Follow-up at our unit has been arranged. Figure 1: Cerebral computed tomography of a 40-year-old man showing generalized cerebral atrophy, bilateral basal ganglia calcification (asterisks) and a left parieto-occipital hypodensity (arrow).\"}", "questions": ["What mitochondrial supplement was initiated for the patient?"], "ground_truth_arguments": ["treatment with coenzyme Q 10 was started"]}
{"id": "CaseReportBench:train-268", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case report': \"A 16-year-old Iraqi boy, born of first-cousin parents, presented to our outpatient clinic at Al-Sadr Teaching Hospital with hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing. He also had hearing loss, speaking difficulties, premature graying of the hair, gynecomastia, corneal arcus, hypospadias, and finger and toe deformities (hallux valgus). These features started at age 10, except for the hypospadias, which was present since birth, and the hearing loss and speaking difficulties, which were diagnosed in early childhood. The mother stated that the child delayed walking until the age of 2 years, and she reported that he had a severe ear infection by the age of 6. The patient has 3 brothers and 2 sisters; his older brother has bilateral swelling of the feet and deformities of the toes, but the patient's other siblings are all healthy. See Table I for clinical examination findings ( Fig 1, Fig 2, Fig 3 ). Table I Findings on examination Examination Findings Vital signs Pulse rate, 83 beats per minute; blood pressure, 100/70 mmHg; respiratory rate, 13 breaths per minute; and temperature, 37°C Anthropometric parameters Weight, 47.1 kg; height, 160 cm; MUAC, 19.3; BMI, 18.4; height/age, -1.7 SD; BMI/age, -0.9 SD Skin Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well-demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees (see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt-and-pepper gray hair (see Fig 2 ) Head OFC, 51 cm (-2.8 SD, <1 st percentile); face looks flat; ears are of abnormal shape and size. Eyes Bilateral corneal arcus; moderate exophthalmos; asymmetrical corneal light reflex. Ophthalmoscopic examination showed bilateral swelling of the optic disc. Visual acuity is normal. Hearing assessment Severe hearing loss Breast Bilateral gynecomastia Heart Normal Abdomen Mild hepatosplenomegaly Lymph nodes Severely enlarged inguinal lymph nodes, with tenderness on palpation Genitourinary Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal. Musculoskeletal Bilateral hallux valgus deformity, with fixed flexion contractures, in the interphalangeal joints of the toes and the little fingers (see Fig 3 ). There is also a nonpitting edema of the ankles. BMI, Body mass index; MUAC, mid-upper arm circumference; OFC, occipitofrontal circumference. Fig 1 Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees. Fig 2 Posterior view of the patient's head shows salt-and-pepper gray hair. Fig 3 Hallux valgus deformity, with flexion contractures of the toes and little fingers. Laboratory test results showed elevated erythrocyte sedimentation rate of 93 (normal range, 0–15 mm/h), elevated serum cortisol of 1030 nmol/L (normal range at morning, 171-536 nmol/L), and decreased serum testosterone level of 2.63 ng/mL (normal range, 2.8-8 ng/mL). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti–double-stranded DNA, anti-cyclic citrullinated peptide, and lipid profile all were normal. Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal, and pure tone audiometry found bilateral profound mixed hearing loss. Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes (see Fig 4 ). The biopsy was taken from the hyperpigmented patch on the medial aspect of the right thigh. Fig 4 Immunohistochemistry stain shows diffuse infiltration of histiocytes. (CD68 + ; original magnification: ×400.)\"}", "questions": ["Describe any breast changes noted in the examination.", "Describe the patient's secondary sexual characteristic findings.", "Provide the serum cortisol and testosterone concentrations and comment on whether they are within normal limits."], "ground_truth_arguments": ["gynecomastia", "pubic hair presents in normal distribution", "elevated serum cortisol of 1030 nmol / L ( normal range at morning, 171 - 536 nmol / L ), and decreased serum testosterone level of 2.63 ng / mL ( normal range, 2.8 - 8 ng / mL )"]}
{"id": "CaseReportBench:train-147", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as \"disease causing\" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most \"likely damaging\" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}", "questions": ["What findings regarding hirsutism were reported for the patients?"], "ground_truth_arguments": ["no hirsutism"]}
{"id": "CaseReportBench:train-169", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Chief complaints': 'Recurrence of abdominal pain, nausea, and vomiting in a kidney transplant patient.', 'Personal and family history': 'The patient had no known family history of porphyria.', 'CASE SUMMARY': 'The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro-pathy. He subsequently developed diabetes mellitus which required insulin therapy. He had been treated in the recent past with local mesalamine for proctitis. He presented with classic but common symptoms of AIP including intense abdominal pain, hypertension, and anxiety. He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained. His urinary postprandial blood glucose level was 60 mg/24 h (normal, < 2 mg/24 h). He was placed on a high carbohydrate diet, and his symptoms slowly improved.', 'Physical examination': 'The patient was hemodynamically stable with a heart rate of 90 bpm and blood pressure of 160/90 mmHg, but appeared in mild distress. The physical examination revealed an intermittently tender, non-distended abdomen with normal bowel sounds and absent rigidity, rebound, and guarding. The remainder of the physical exami-nation was unremarkable.', 'Imaging examinations': 'Plain X-rays of the abdomen showed distended colon and fecal impaction, and ultrasound revealed that the liver, spleen, pancreas, and transplanted kidney were of normal size and consistency and that the site of the left nephrectomy was occupied by intestinal loops.', 'Laboratory examinations': 'Serum levels of hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C-reactive protein were normal, as was the urine analysis. Renal function was stable with a serum creatinine of 1.2 mg/dL; the urine culture was negative.', 'History of present illness': 'A 65-year-old man reported the appearance of rectal blood in March 2017 and visited a proctologist. He started local mesalamine therapy for proctitis, but the drug was discontinued a few days later due to abdominal pain and constipation. During the subsequent 6 mo, he presented several times to the emergency department complaining of severe abdominal pain, nausea, and vomiting. He related an anxious mood and low energy level in addition to tachycardia and an increase in blood pressure which was no longer well-controlled with his usual therapy. He presented to the emergency room eight times for various complaints (Figure 1 ): Epigastric pain without mention of mesalamine, agitation and anxiety, thoracic pain, abdominal pain, and precordial pain.', 'History of past illness': 'The patient had been treated for hypertension since 1994 and developed ischemic heart disease. His renal function gradually deteriorated over the years due to suspected nephroangiosclerosis and chronic interstitial nephropathy, as ultrasound examination demonstrated small echogenic kidneys. He started hemodialysis in 2008 and was evaluated for renal transplantation; a left nephrectomy was performed for a small incidental renal carcinoma. The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis. He underwent a deceased-donor kidney transplant in 2015, for which he was treated with tacrolimus, mycophenolate mofetil, and methylprednisolone. He developed diabetes mellitus post-transplant and insulin therapy was initiated (see Table 1 ).'}", "questions": ["What was the patient's age at the time of presentation?"], "ground_truth_arguments": ["65 - year - old", "65 - year - old"]}
{"id": "CaseReportBench:train-320", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': \"A 21-year-old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009. Emergent colonoscopy was performed with the findings of (1) a large amount of blood in the rectum and sigmoid colon and (2) oozing from eroded rectal mucosa. Laboratory investigation revealed thrombocytopenia (platelets 10.3 × 10 4 / μl). Although the hemorrhage stopped spontaneously and did not occur again, the patient was referred to our hospital for further examinations. He had had no previous significant rectal bleeding. His past medical history was unremarkable except for occasional nasal bleeding during childhood. On physical examination, the abdomen was soft and flat; a non-tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin. Neurologic examination revealed no evidence of abnormalities. The laboratory data are summarized in table 1 . There were thrombocytopenia and slight leukocytopenia (platelets 6.7 × 10 4 /μl, white blood cells 3,180/μl). Other laboratory findings disclosed: total bilirubin 1.4 mg/dl (reference range 0.2–1.3), direct bilirubin 0.5 mg/dl (reference range 0–0.3), and prothrombin time activity 77.0% (reference range 90–130). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein-Barr virus and Helicobacter pylori ; however, there were no remarkable findings. Anti-DNA antibody test showed a titer of 1:40 (reference range <1:40). His platelet-associated immunoglobulin G (PAIgG) level was elevated to 166 ng/10 7 cells (reference range 9.0–25.0), however anti-platelet antibody (anti-platelet-binding IgG) was negative. Enhanced computed tomography (CT) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed (fig. 1a ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson's capsule (fig. 2 ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin-converting enzyme (ACE) concentrations (table 1 ), which is compatible with Gaucher disease. The enzymatic activity of leukocyte β-glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol/h/mg (reference range 56.76–74.85). We analyzed the seven common mutations (N370S, 84GG, F213I, IVS2+1, L444P, R463C and D409H) in the GBA gene as previously reported with the informed consent of the patient and found the compound heterozygous mutations L444P/D409H. Based on these results, we diagnosed the patient with Gaucher disease type 1. We started enzyme replacement therapy (ERT). 60 U/kg body weight imiglucerase, a macrophage-targeted recombinant human glucocerebrosidase, was injected every 2 weeks. Figure 1b shows the CT scan 5 months after ERT started. The liver and the spleen were sized down (liver: from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen: from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease, were also improved from 7.4 to 11.3 × 10 4 /μl and from 42.5 to 24.7 IU/μl, respectively (fig. 3 ).\"}", "questions": ["What basic demographic and admission information is reported for the patient (e.g., age, sex, presenting complaint, and admission date)?", "What prior history of rectal bleeding, if any, did the patient have before this sudden hemorrhage?", "What elements of the patient’s past medical history are noted, including any childhood bleeding episodes?"], "ground_truth_arguments": ["A 21 - year - old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009", "no previous significant rectal bleeding.", "His past medical history was unremarkable except for occasional nasal bleeding during childhood"]}
{"id": "CaseReportBench:train-483", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made. Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years. There was no other significant positive clinical findings. Case three was a 14-year-old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia. Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth. On examination, he had molluscum contagiosum lesions on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case. Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis. Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern. The features of all these five cases have been summarized in Table 1 .'}", "questions": ["What are the ages of the patients as explicitly stated in the form \"X‑year‑old\" in each case description?", "From the ages obtained, exclude any ages that belong to cases where the description mentions verruca vulgaris, growth retardation, or mental retardation."], "ground_truth_arguments": ["30 - year - old", "22 - year - old", "9 - year - old", "21 - year - old"]}
{"id": "CaseReportBench:train-331", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A one-and-half year old boy presented with generalized scaling over whole body and redness over both cheeks. There was a history of consanguineous marriage and prolonged labor and baby was delivered by normal vaginal delivery. The birth weight of the baby was 2.3 kg and the length of the baby was 36 cm. There was no history suggestive of collodion membrane. Scaling started from 3 weeks of age and had a history of exacerbation in the winter and improvement in summer. Immunization was completed according to the immunization schedule. There was no family history of similar kind of illness. There was no history of any drug intake prior to the scaling or atopic diathesis. On examination there was fine white to brown scaling over the whole body without any spared area with glistening surface over palms and soles with involvement of flexures. On the scalp fine whitish-grey and grayish brown scaling was present and in some areas there was thick crusting which on removal revealed a moistened surface. On the frontal scalp margin, there were large grayish-brown ichthyotic scales. Both the cheeks were erythematous along with scaling and scales also involved the upper eyelid, upper lips and over the nose. There was no abnormality in the eyes except mild ectropion. There was no evidence of seborrheic blepharitis. Left-sided cryptorchidism was present for which the patient was referred to pediatric surgery and they have suggested waiting for another 6 months after which they would suggest surgical intervention. Ophthalmological examination was done and no abnormality found. Blood investigations, chest X-ray, urine examination showed no abnormality. Histopathological examination was done which revealed mild hyperkeratosis. As it is not confirmatory and does not help in making the diagnosis, we made a diagnosis of erythroderma due to X-linked ichthyosis as there were components of history of consanguinity and prolonged labor and examination showed cryptorchidism and generalized scaling with flexural involvement. The patient was prescribed emollient and urea 10% cream and after 4 weeks he showed improvement in scaling and oral retinoid was not needed.'}", "questions": ["What were the findings of the eye (ophthalmological) examination, including any reported abnormalities or the statement that no abnormality was found?"], "ground_truth_arguments": ["no abnormality in the eyes except mild ectropion. There was no evidence of seborrheic blepharitis", "Ophthalmological examination was done and no abnormality found"]}
{"id": "CaseReportBench:train-226", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Cases': 'The older patient was 20 years old. She was a product of a full-term spontaneous vaginal delivery at home. She was found to have severe virilized external genitalia: a phallic-like structure with hypospadias and incompletely fused labioscrotal folds. She was raised and named as a boy and no medical advice was sought at that time. Her parents reported that she had behaved as a female since early childhood. She was interested in playing with girls and in girl’s games, although she studied at male schools. She spent most of her time with her girlfriends and felt most comfortable when she dressed as a female. She was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation. Physical examination showed a short male-looking adolescent with acne and Tanner stage IV breast development. Her height was 133 centimeters. Her blood pressure was 140/88. Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An adrenocorticotropic hormone (ACTH) stimulation test showed a baseline cortisol (F) level of 28 nmol/L, ACTH of 201 ng/mL (normal, 0–46), 11-deoxycorticosterone (11-DOC) of 20 nmol/L (normal, 0.49–3.3), 17-hydroxyprogesterone (17-OHP) of 17 nmol/L and testosterone (T) of 7 nmol/L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol/L, the 11-DOC level was 141 nmol/L (normal, 2.2–6.8) and the 17-OHP level was 22 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X-ray. Examination under anaesthesia combined with cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus. Based on her biochemical and radiological evaluation, she was diagnosed as having 11-hydroxylase deficiency and was started on hydrocortisone 10 mg twice a day. She was evaluated by the pediatric psychiatrist who clearly confirmed her female gender identity and her strong wish to be converted to a female. Feminizing genitoplasty (clitoral reccesion) was performed at the age of 16 years and she was given a female name. She admitted her strong desire to get married and to be a mother. The younger patient was 16 years old. He was born at home and raised and named as a boy based on the appearance of the external genitalia. His parents reported that he behaved as a male and was proud of that. He was interested in playing with boys and in boy’s sports. He was dressed as a boy and had a short haircut. He was referred to our clinic at the age of 13 years. Physical examination showed a short stature, a masculine appearance, acne and Tanner stage IV pubic hair and stage II breast development. His height was in the fifth centile. His blood pressure was 130/80 mm Hg. Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol/L, an ACTH of 231 ng/mL, 11-DOC of 40 nmol/L, 17-OHP of 18 nmol/L and a T level of 7 nmol/L. Sixty minutes after ACTH stimulation, the F level was 45 nmol/L, 11-DOC was 114 nmol/L and 17-OHP was 20 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years. He was diagnosed as having 11-hydroxylase deficiency and started on hydrocortisone 10 mg twice a day. His final height was 139 centimeters. He was interviewed by the pediatric psychiatrist who clearly confirmed his male gender identity and his strong wish to continue to be raised as a boy. We had several separate meetings with him and his parents and informed them that he would be an infertile man if he decided to continue to be raised as a man and there was a possibility that he would be a fertile women if he converted to his genetic sex. The patient, however, refused to change to his female genetic sex and admitted his strong wish to be a man forever. After more that one year of counseling and intensive psychiatric interview, he and his parents decided on a hysterectomy “to avoid menarche which might affect him psychologically” as his mother said. Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed. Both patients were satisfied by the way they were managed and raised and there were no postoperative psychological complications.'}", "questions": ["What medication and dosage were initiated for the patients diagnosed with 11‑hydroxylase deficiency?"], "ground_truth_arguments": ["was started on hydrocortisone 10 mg twice a day", "started on hydrocortisone 10 mg twice a day ."]}
{"id": "CaseReportBench:train-508", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}", "questions": ["At what age did the female patient first present with poor weight gain and signs of CGL?", "At what age did the male patient first show reduction of subcutaneous adipose tissue and other CGL symptoms?"], "ground_truth_arguments": ["1 mo of age .", "3 mo of age"]}
{"id": "CaseReportBench:train-181", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': \"An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.\", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}", "questions": ["What are the patient's demographic details and presenting complaints?"], "ground_truth_arguments": ["An 18 - year - old woman came in with swelling in her ankles and a cognitive decline"]}
{"id": "CaseReportBench:train-115", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case report': 'We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. The Saudi female patient in the UK developed recurrent bouts of abdominal pain, nausea, and vomiting during first pregnancy, diagnosed as hyperemesis gravidarum, and was treated with IV fluids and antiemetics. There was improvement in the condition and the patient delivered a healthy child (in Saudi). After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatremia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities. She was intubated for 3 days. Initial postextubation, physical examination result was unremarkable except for unexplained behavioral disturbances and lower limb weakness. Initial instigations showed sodium levels ranged between 118–125 mmol/L (135–144 mmol/L), mildly elevated transaminases (aspartate aminotransferase/alanine transaminase), and slight elevation of anti-neutrophil antibodies of the perinuclear type (P-ANCA). Alkaline phosphatase, bilirubin, complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid (CSF) analysis findings were all within normal range. The abdominal imaging result was normal, except for contracted gallbladder and stones. Urine became dark red on exposure to light. Total porphyrins in urine were elevated: 29,100 nmol/24 hours (normal: ≤214), with main elevation in uroporphyrin level, 24,200 nmol/24 hours (normal: ≤30), and mild elevation in coproporphyrin level, 118 nmol/24 hours (normal: ≤38). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene (c. 760delC p.L254X). The patient was treated with intravenous heme arginate (4 mg/kg/day) for 5 days, that was followed by an improvement in the chemical and clinical parameters.'}", "questions": ["What type of gastrointestinal symptoms, if any, did the patient report during her first pregnancy?", "What was the overall outcome of the patient's first pregnancy?"], "ground_truth_arguments": ["abdominal pain, nausea, and vomiting during first pregnancy", "patient delivered a healthy child"]}
{"id": "CaseReportBench:train-14", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE': 'A 56-year-old man, who had been a heavy drinker, presented symptoms of general weakness, abdominal discomfort, diarrhea and weight loss and was admitted to the hospital. On examination, he was found to be cachectic and his abdomen slightly distended with shifting dullness. Laboratory examination revealed a hemoglobin level of 13.1 g/dL; white blood cell count, 17,800/mm 3 ; platelet count, 553,000/mm 3 ; albumin, 2.6 g/dL; total bilirubin, 0.3 mg/dL; GOT, 48 IU/L; GPT, 22 IU/L; and alkaline phosphatase, 117 IU/L. His serum amylase was 856 IU/L and serum lipase 1,077 IU/L. A computed tomographic (CT) scan of the abdomen ( Figure 1 ) revealed evidence of acute exacerbated, chronic pancreatitis, including pseudocysts, one of which was approximately 7 cm in diameter and was located in the tail of the pancreas with adjacent splenic vein occlusion. In addition, right portal vein occlusion, with corresponding perfusion defect and liver infarction, was noted. The patient was treated initially with intravenous fluids, antibiotics and TPN. Two weeks after treatment including TPN, the patient exhibited multiple skin lesions and continued to experience diarrhea more than 10 times daily. These skin lesions were vesiculopustular and erythematous eruptions with scales on the face ( Figure 2A ) and perineal areas. During the following week, the lesions spread to involve the hands and feet ( Figure 2B, 2C ). He became depressed and agitated. In view of typical skin lesions, mental change and protracted diarrhea, we strongly suspected acrodermatitis enteropathica due to zinc deficiency. His serum zinc level was found to have fallen to 17.4 μ g/dL (normal range, 70 to 150 μ g/dL) and, therefore, we initiated therapy with zinc sulfate at 5 mg daily. Three to four days of zinc supplementation produced marked improvement of the diarrhea and, after one week of zinc supplementation, the skin lesions began to alleviate. The patient continued to do well until five weeks after TPN when abdominal pain and fever developed. With strong suspicions of an infected pancreatic pseudocyst, we performed an abdominal CT scan and subsequently a percutaneous pigtail insertion to drain the pseudocyst. Soon thereafter, he felt well with no pain or fever. A repeat CT scan 10 days later showed total collapse of the pseudocyst and resolution of the PVT and liver infarction. On the 74th hospital day, he was discharged without any problem. By this time, his skin lesions had almost healed.'}", "questions": ["What was the patient's age at the time of presentation?"], "ground_truth_arguments": ["56 - year - old"]}
{"id": "CaseReportBench:train-490", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case report': 'An 11-year-old male had presented to the hospital with a history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4-5 years. There was no history of fever or localized pain. On examination, the blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg (75th-90th centile) and his height measured 138 cm (50th centile). Generalized skin hyperpigmentation was present. Systemic examinations were normal. Local examination revealed bilateral scrotal swelling with normal-appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia (testis length 3.5 cm, penile length 10 cm) and stage 3 for pubic hair. The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size (right and left testicular volume – 2.9 mL and 2.8 mL respectively) with multiple well-defined round to oval hetero-echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B). On screening abdominal sonography, a large well-defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity ( Figs. 3 A and B). Based on these findings, the possibility of testicular malignancy with adrenal metastasis was considered. Contrast-enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands (left>right) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C). Serum tumor markers (alpha-fetoprotein, LDH, and Beta hCG) were negative hence, the diagnosis was reconsidered for the possibility of testicular adrenal rest tumors in an undiagnosed case of congenital adrenal hyperplasia. Fig. 1 (A) Grayscale US of scrotum showing normal-sized right testis with heterogeneous appearance. (B) US image of bilateral testes with multiple nodules containing tiny calcific foci (black arrow). Fig 1 Fig. 2 (A) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. (B) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 (A) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions (white arrow). (B) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions (white arrow). Fig 3 Fig. 4 (A) Contrast enhanced computed tomography (CECT) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia (White arrows). (B) CECT pelvis axial section showing multiple enhancing nodules in the right testis (black arrow). (C) CECT pelvis axial section showing multiple enhancing nodules in left testis (black arrow). Fig 4 X-ray left wrist AP/lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq/L (normal range: 3.5-4.5 mEq/L), whereas the sodium level remained within normal limits at 140 mEq/L. There was a significantly heightened level of 17-hydroxyprogesterone at 1800 ng/dL (normal range: <110 ng/dL), accompanied by normal levels of lactate dehydrogenase (LDH), beta-human chorionic gonadotropin hormone (B-HCG), and alpha-fetoprotein (AFP). Additionally, the serum adrenocorticotropic hormone (ACTH) concentration was elevated, measuring 564 pg/mL (normal range: 7.2-63.3 pg/mL), while cortisol levels were diminished, measuring 5.7 µg/dL (normal range: 7-25 µg/dL). Dehydroepiandrosterone sulfate (DHEA-S) was measured at 5.25 µmol/L (normal range: ≤ 3.726 µmol/L), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng/dL (normal range: 31-65 ng/dL), and there was a reduced level of Inhibin B, measuring 71.1 pg/mL (normal range: 240-445 pg/mL). Collectively, these findings point towards a diagnosis of congenital adrenal hyperplasia. The patient is currently undergoing treatment with hydrocortisone and is on regular follow-up. The 3-month follow-up revealed clinical improvement with a reduction in testis size and decreased ACTH levels, indicating positive progress. Fig. 5 X-ray of left wrist AP and a lateral view showing accelerated bone age corresponding to approximately 18 years. Fig 5', 'Patient consent': 'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.'}", "questions": ["How was the patient's blood pressure described for each arm?", "How were the patient's weight, height, and growth centile information reported?", "How were the non‑blood‑pressure vital signs described in terms of stability or abnormality?"], "ground_truth_arguments": ["blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg ( 75th-90th centile ) and his height measured 138 cm ( 50th centile )"]}
{"id": "CaseReportBench:train-514", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Patient consent statement': 'Parents of patient have given consent to publish the case report.', 'Case report': 'A 14-year-old girl presented in Dermatology outpatient department, with a few skin lesions over face and anterior aspect of her neck for one month ( Fig. 1 ). The lesions measured approximately 2–5 mm in size. A history of pruritis was present. Clinically, differential diagnosis of Milia over erythematous base was suggested. A history of skin laxity or joint hypermobility was absent. The general physical examination and systemic examination were within the normal limit. Family history was not significant. The clinician kept Milia en plaque and Pseudoxanthoma elasticum as differential diagnosis. A punch biopsy of the lesions was performed, and the tissue was sent for histopathological analysis to confirm the clinical diagnosis. Fig. 1 2–5 mm lesions (milia) over face. Fig. 1 Hematoxylin and eosin (H&E) stained microsections examined from the skin biopsy submitted showed, a prominent granular layer with mild spongiosis and basal layer vacuolization. The papillary dermis was mildly edematous with evidence of mild lymphoplasmacytic infiltrate along with few histiocytes. The mid and lower dermis revealed a prominent zone of chronic inflammatory infiltrate comprising of lymphocytes, histiocytes, and occasional plasma cells. Giant cells were also evident in the mid-dermis. In the middle reticular dermis, deposition of basophilic mucoid material along with haphazardly arranged clumped fragmented elastic fibres were seen. This basophilic mucoid material stained positive for alcian blue, colloidal iron, and Von-Kossa ( Fig. 2 ). The adnexal structures and subcutaneous adipose tissues were essentially unremarkable. Staining for acid-fast bacilli was non-contributory. Based on characteristic histopathology features, a diagnosis of PXE was offered. Fig. 2 Hematoxylin and Eosin stained section of skin biopsy showed (a) upper and mid dermis (demarcated by black line) involved with a prominent chronic inflammatory infiltrate, (b) Deep basophilic mucoid material in dermis (demarcated by arrow mark & star mark) stained positive for alcian blue and, (c) colloidal iron and, (d) Fragmentation and calcification of dermal elastic fibers is evident on Von Koss stain. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.) Fig. 2'}", "questions": ["What diagnosis was concluded from the characteristic histopathology features observed in the skin biopsy?", "Which specific disease was identified based on the histopathological findings described in the case report?", "How did the histopathology results influence the final diagnostic decision for the patient?"], "ground_truth_arguments": ["Based on characteristic histopathology features , a diagnosis of PXE was offered"]}
{"id": "CaseReportBench:train-288", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Description': 'The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like “X”-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS).', 'Case presentation': 'A 32-year-old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient’s visit to our hospital. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Oral informed consent was obtained from the patient. On the patient’s maternal side, there was a history of rectal cancer (the patient’s grandmother, an uncle, and an aunt), uterine cancer (a 29-year-old female cousin), rectal cancer with uterine cancer (two aunts), and colon polyposis (a 29-year-old male cousin) ( Figure 1A ). A physical examination showed mild tenderness only in the right lower abdomen. No significant abnormalities were found in serum tumor markers. A colonoscopy revealed a cauliflower-like mass at the beginning of the ascending colon ( Figure 1B ). Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast-enhanced computed tomography (CT) showed ascending colon cancer with intussusception ( Figure 1D ). The preoperative diagnosis was cT3N0M0 colon cancer, according to the TNM classification. On August 27, 2021, the patient underwent laparoscopic radical right hemicolectomy under general anesthesia. During the operation, we found that there were two ICAs derived from the SMA, with the ileocolic vein (ICV) crossing anterior to the SMA ( Figure 2A ). The right colic vein was also absent ( Figure 2B ). The gastrocolic trunk of Henle was draining into the superior mesenteric vein (SMV), which was joined by the right gastroepiploic and colic veins, the anterior superior pancreaticoduodenal vein, and the superior right colic vein ( Figure 2C ). Furthermore, the SMA and SMV were found to be accompanied like “X”-shaped variant ( Figure 2D ). As we saw in the surgery，abdominal contrast-enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery (RCA) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C ). We summarized the schematic diagram of vascular variation of this patient ( Figure 3D ). The patient was discharged on the fourth day after surgery. Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient’s tumor sample ( Figure 5C,5D ). Given the patient’s family history of cancer, we highly suspected Lynch syndrome (LS). Next-generation sequencing (NGS), performed by 3D Medicines Inc. (Shanghai, China), was used to analyze tumor and blood samples from the patient. As shown in Figure 6, the results revealed MLH1 c.885-1_893del, which may represent a change in the conformation of the acceptor splicing site, which may have impeded mRNA formation, eventually leading to deficient mismatch repair. Seven weeks after surgery, the patient was administered a regimen of adjuvant chemotherapy with CapeOX (day 1, oxaliplatin 130 mg/m 2, day 1 to 14 capecitabine 1,000 mg/m 2, po, twice a day, every 3 weeks) for four cycles. Four months after the end of chemotherapy, CT reexamination showed no tumor recurrence ( Figure 7 ).'}", "questions": ["What vascular anomalies were identified on preoperative contrast‑enhanced CT and intraoperative imaging?", "What is the final surgical pathological diagnosis, including tumor type, differentiation, and stage, for the ascending colon cancer?", "What were the results of serum tumor marker testing in this patient?", "What did the preoperative colonoscopic biopsy reveal about tumor differentiation, and what did the preoperative contrast‑enhanced CT show regarding the tumor?", "What arterial and venous configurations were observed during surgery and on postoperative imaging?", "What were the detailed surgical pathology findings, including tumor histology, stage, and immunohistochemical profile?", "What genetic alteration was identified by next‑generation sequencing?"], "ground_truth_arguments": ["Preoperative abdominal contrast - enhanced computed tomography ( CT ) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery ( SMA ). On the other side, the SMA and superior mesenteric vein ( SMV ) were found to be accompanied like “ X”-shaped variant", "The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon", "No significant abnormalities were found in serum tumor markers", "Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast - enhanced computed tomography ( CT ) showed ascending colon cancer with intussusception", "surgery，abdominal contrast - enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery ( RCA ) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C )", "Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer ( AJCC ) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient ’s tumor sample", "the results revealed MLH1 c.885 - 1_893del"]}
{"id": "CaseReportBench:train-368", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case report': \"A 16-year-old Iraqi boy, born of first-cousin parents, presented to our outpatient clinic at Al-Sadr Teaching Hospital with hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing. He also had hearing loss, speaking difficulties, premature graying of the hair, gynecomastia, corneal arcus, hypospadias, and finger and toe deformities (hallux valgus). These features started at age 10, except for the hypospadias, which was present since birth, and the hearing loss and speaking difficulties, which were diagnosed in early childhood. The mother stated that the child delayed walking until the age of 2 years, and she reported that he had a severe ear infection by the age of 6. The patient has 3 brothers and 2 sisters; his older brother has bilateral swelling of the feet and deformities of the toes, but the patient's other siblings are all healthy. See Table I for clinical examination findings ( Fig 1, Fig 2, Fig 3 ). Table I Findings on examination Examination Findings Vital signs Pulse rate, 83 beats per minute; blood pressure, 100/70 mmHg; respiratory rate, 13 breaths per minute; and temperature, 37°C Anthropometric parameters Weight, 47.1 kg; height, 160 cm; MUAC, 19.3; BMI, 18.4; height/age, -1.7 SD; BMI/age, -0.9 SD Skin Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well-demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees (see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt-and-pepper gray hair (see Fig 2 ) Head OFC, 51 cm (-2.8 SD, <1 st percentile); face looks flat; ears are of abnormal shape and size. Eyes Bilateral corneal arcus; moderate exophthalmos; asymmetrical corneal light reflex. Ophthalmoscopic examination showed bilateral swelling of the optic disc. Visual acuity is normal. Hearing assessment Severe hearing loss Breast Bilateral gynecomastia Heart Normal Abdomen Mild hepatosplenomegaly Lymph nodes Severely enlarged inguinal lymph nodes, with tenderness on palpation Genitourinary Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal. Musculoskeletal Bilateral hallux valgus deformity, with fixed flexion contractures, in the interphalangeal joints of the toes and the little fingers (see Fig 3 ). There is also a nonpitting edema of the ankles. BMI, Body mass index; MUAC, mid-upper arm circumference; OFC, occipitofrontal circumference. Fig 1 Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees. Fig 2 Posterior view of the patient's head shows salt-and-pepper gray hair. Fig 3 Hallux valgus deformity, with flexion contractures of the toes and little fingers. Laboratory test results showed elevated erythrocyte sedimentation rate of 93 (normal range, 0–15 mm/h), elevated serum cortisol of 1030 nmol/L (normal range at morning, 171-536 nmol/L), and decreased serum testosterone level of 2.63 ng/mL (normal range, 2.8-8 ng/mL). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti–double-stranded DNA, anti-cyclic citrullinated peptide, and lipid profile all were normal. Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal, and pure tone audiometry found bilateral profound mixed hearing loss. Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes (see Fig 4 ). The biopsy was taken from the hyperpigmented patch on the medial aspect of the right thigh. Fig 4 Immunohistochemistry stain shows diffuse infiltration of histiocytes. (CD68 + ; original magnification: ×400.)\"}", "questions": ["Describe the cutaneous lesions, including their color, induration, distribution, symmetry, any spared areas, and associated hypertrichosis.", "Explain how the skin lesions evolved over time, noting the initial presentation and subsequent changes.", "Detail the hair findings, including any color changes, pattern, and timing of these changes.", "Summarize the facial and ear morphological features noted on examination.", "What breast findings are reported for the patient?", "Summarize the histopathology findings of the skin biopsy, focusing on dermal fibrosis, collagen changes, and cellular infiltrates.", "What did immunohistochemical staining reveal about the cellular composition of the lesion?"], "ground_truth_arguments": ["hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing", "premature graying of the hair", "Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well - demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees ( see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt - and - pepper gray hair", "face looks flat; ears are of abnormal shape and size", "Bilateral gynecomastia", "Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees", "salt - and - pepper gray hair", "Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes", "Immunohistochemistry stain shows diffuse infiltration of histiocytes"]}
{"id": "CaseReportBench:train-23", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case report': \"We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).\", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}", "questions": ["What eye-related manifestations (e.g., retinal and vitreous findings) are documented for the patient?"], "ground_truth_arguments": ["angioid streaks, atrophic retinal break of the right eye,", "vitreous degeneration, and bilateral posterior vitreous detachment"]}
{"id": "CaseReportBench:train-585", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'CASE REPORT': 'A 4-year-old female patient with a nasal anomaly was admitted to our outpatient clinic. She was born 2300 g prematurely on her 37 th gestational week from a 34-year-old mother with a history of five pregnancies, two still births and two abortions. On her physical examination, she had a left-sided supernumerary nostril and cliteromegaly. Her laboratory studies revealed low levels of androstenedione and her history showed that she had medical therapy for 1 year for her congenital adrenal hyperplasia. No additional anomaly except patent foramen ovale was detected in her work-ups. Paranasal sinus computed tomography study revealed that her left-sided accessory nostril opened to the left nasal cavity. The patient was operated, the opening of the supernumerary nostril to the nasal cavity was obliterated and the widened nostril was narrowed by excisions from the alar ground and lateral side. A revision toward the nostril asymmetry is planned 1 year after the operation.'}", "questions": ["What was the patient's birth weight and gestational age at delivery?", "What was the mother's age at the time of the patient's birth?", "How many pregnancies, stillbirths, and abortions had the mother experienced prior to this child's birth?"], "ground_truth_arguments": ["She was born 2300 g prematurely on her 37 th gestational week from a 34 - year - old mother with a history of five pregnancies, two still births and two abortions"]}
{"id": "CaseReportBench:train-435", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["Provide the patient’s demographic information (age, gender, country of origin) and summarize the initial neurological symptoms and any associated prodromal complaints such as headache, nausea, or dizziness.", "List the patient’s pre‑existing medical conditions and any sensory impairments, noting the control status of chronic diseases and the use of assistive devices.", "Describe the neurological deficits observed on admission, focusing on language, speech, and motor findings.", "Summarize the events that occurred around hospital day 4, including the patient’s discharge disposition, any subsequent seizure activity, and the timing of readmission.", "What does the three‑generation family history reveal about any known neurologic, muscular, cardiac, or visual problems in the patient’s relatives?"], "ground_truth_arguments": ["A 48 - year - old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word - finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness.", "Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years", "moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity.", "On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic – clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night.", "A detailed 3 - generation family history revealed no known neurologic, muscular, cardiac, or vision problems"]}
{"id": "CaseReportBench:train-406", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["What demographic information is provided for Patient 1 in the case description?"], "ground_truth_arguments": [", 68 years old"]}
{"id": "CaseReportBench:train-446", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': \"An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.\", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}", "questions": ["What age group does the patient belong to at the time of presentation?"], "ground_truth_arguments": ["18 - year - old"]}
{"id": "CaseReportBench:train-429", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'The patient was a 41-year-old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age. He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure. His family history was not remarkable. He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age. Three months later, he was admitted to our hospital due to impaired consciousness and vomiting. A neurological examination showed gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities. However, no ophthalmoplegia, hearing loss, or muscle weakness were detected. His mini-mental status examination score was 15/30, and his frontal assessment battery score was 5/18. The findings from routine blood tests including blood sugar and autoimmune antibodies were normal. A laboratory examination showed slightly increased serum pyruvic acid levels (1.2 mg/dL), but his serum lactate levels were normal (14.2 mg/dL). The cerebrospinal fluid lactate (34.8 mg/dL) and pyruvic acid (1.6 mg/dL) levels were elevated. Electrocardiogram and echocardiogram were normal. Brain magnetic resonance imaging (MRI) showed bilateral cortical and subcortical high-intensity lesions on T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion-weighted imaging (DWI) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient (ADC) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H-MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ). 99m Tc-Ethylcysteinate dimer single photon emission computed tomography (SPECT) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions ( Fig. 1E ). We suspected mitochondrial encephalopathy, such as MELAS. A histopathological study of the biopsied right biceps branchii muscle revealed mild variation in the fiber size, measuring from 30 to 90 microns in diameter, which was thought to be a non-specific change. No necrotic or regenerating fibers were seen. On modified Gomori-trichrome stain, ragged red fibers (RRFs) were not observed. Succinate dehydrogenase (SDH) stain revealed no strongly SDH-reactive blood vessels. Cytochrome c oxidase staining revealed no abnormalities ( Fig. 1F ). However, the complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a level of mutant heteroplasmy of 69.5%, in the mitochondrial complex I subunit gene, MT-ND3 ( Fig. 1G ). Because his family had no clinical symptoms suggestive of mitochondrial diseases, we could not conduct a complete mtDNA sequence analysis of his family. Over a two-month period, he experienced two stroke-like episodes with simple partial seizure and vomiting. Each time the stroke-like episodes ended within four days with drip infusion of edaravone and supportive care. To control epileptic seizure, we added levetiracetam (1,000 mg/day) to zonisamide (400 mg/day) and carbamazepine (400 mg/day). Because he had not yet been diagnosed with MELAS-like encephalopathy at that time, we did not administer L-arginine. His higher brain dysfunction and myoclonus worsened with each stroke-like episode.'}", "questions": ["What is the patient's age group at the time of presentation?"], "ground_truth_arguments": ["41 - year - old"]}
{"id": "CaseReportBench:train-558", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 57-year-old woman presented with a history of multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs. The patient was referred from the neurology department for management of these painful masses, which were obstructing her ability to breath and sleep, forcing her to require home oxygen and a wheelchair for ambulation. She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back. Our patient reported a history of myoclonus epilepsy with ragged red fibers (MERRF) syndrome with symptoms including cardiomyopathy, peripheral neuropathy, ataxia, muscle weakness, and myoclonus. She reported multiple family members having MERRF syndrome including her mother, maternal grandmother, maternal great grandmother, sisters, brothers, her sons, and nephews with variable presentations and lipomas. Physical examination found the patient seated in a wheelchair on supplemental oxygen. Multiple symmetric large, variably sized tender masses were easily apparent and palpable around her neck, upper back, upper lateral arms, mid and lower back, lower abdomen, and upper thighs ( Fig 1, Fig 2, Fig 3 ). Fig 1 Frontal view. Patient with symmetric supraclavicular lipomatosis. Fig 2 Posterior neck. Upper back buffalo hump lipomatosis. Fig 3 Lateral view. Symmetric lipomatosis of upper arms.'}", "questions": ["What demographic details and characteristics of the patient's subcutaneous masses are reported, and how do these masses affect her breathing, sleep, and ability to sit or lie down?", "What clinical manifestations of MERRF syndrome does the patient report, including any cardiac, peripheral nervous system, or muscular findings?", "What family members are noted to have MERRF syndrome, and how do their clinical presentations differ?"], "ground_truth_arguments": ["A 57 - year - old woman presented with a history of multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs. The patient was referred from the neurology department for management of these painful masses, which were obstructing her ability to breath and sleep, forcing her to require home oxygen and a wheelchair for ambulation. She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back", "Our patient reported a history of myoclonus epilepsy with ragged red fibers ( MERRF ) syndrome with symptoms including cardiomyopathy, peripheral neuropathy, ataxia, muscle weakness, and myoclonus", "She reported multiple family members having MERRF syndrome including her mother, maternal grandmother, maternal great grandmother, sisters, brothers, her sons, and nephews with variable presentations and lipomas"]}
{"id": "CaseReportBench:train-428", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["What ocular motor abnormalities (e.g., double vision, ocular misalignment) are described, and what ages are given for their onset?", "What details are provided about ptosis, including laterality and age of onset?", "What details are provided about ophthalmoparesis, including laterality and age of onset?", "Is there any statement that mentions ptosis and ophthalmoparesis together, and what ages are associated with that combined description?"], "ground_truth_arguments": ["divergence of the ocular bulbs with double vision since age 6y", "bilateral ptosis since age 23y,", "ophthalmoparesis since at least age 27y", "ptosis, ophthalmoparesis,", "ophthalmoparesis since age 6y, ptosis since age 23y,"]}
{"id": "CaseReportBench:train-484", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What type of diabetes mellitus is documented for the patient?", "What blood glucose measurements are reported in the case, and at which clinical time points were they recorded?"], "ground_truth_arguments": ["Type I DM.", "hyperglycemia ( 257 mg / dl ),", "her blood sugar was 176 mg / dl.", "her blood sugar level was 120 mg / dl."]}
{"id": "CaseReportBench:train-176", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}", "questions": ["Which therapeutic procedure was performed for the infant diagnosed with neonatal hemochromatosis?", "What immunoglobulin therapy was administered to the infant as part of the medical treatment?"], "ground_truth_arguments": ["Medical treatment was given with exchange transfusion and intravenous immunoglobulin ( IVIg )"]}
{"id": "CaseReportBench:train-510", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Presentation': \"Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment. A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5 th percentile), weight 3000 g (<5 th percentile), and head circumference 36.5 cm (5–10 th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance. Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative. The laboratory tests were as follows: serum sodium 102 meq/lit and serum k + level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1 . Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern. Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed. On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25 th percentile), weight 9.5 kg (10–25 th percentile) and head circumference 46 cm (25 th percentile); her neurodevelopment was appropriate for age.\"}", "questions": ["What abnormal physical examination findings were reported in the infant?", "How was the infant's skin coloration described?"], "ground_truth_arguments": ["pallor and decreased subcutaneous fat and ill appearance with severe dehydration", "skin were obviously jaundiced"]}
{"id": "CaseReportBench:train-398", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Diagnoses:': 'The proband underwent a thorough examination in our hospital and was diagnosed as mitochondrial encephalomyopathy. The proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene. Although his parents did not carry the mutation.', 'Case presentation': \"The proband was a 12-year-old boy on first visiting to our hospital. The proband was the first and the only child of his healthy, nonconsanguineous parents of Han Chinese descentand was born at 38 weeks gestation by spontaneous delivery. The proband had no postnatal adaptation, and the Apgar score was unknown. He was admitted to the hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after the treatment of unexplained fever and somnolence. The highest temperature was 37.8°C, accompanied by vomiting 4 to 5 times on the same day, with insufficient spirits. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of our hospital (no. 2018021). Informed written consent was obtained from all participants prior to their enrollment in this study. The proband underwent a thorough examination in our hospital, including electroencephalogram, echocardiogram, electrocardiogram, brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), physical examination, laboratory examination, and mitochondrial gene detection. Genomic DNA from the family was extracted from peripheral whole blood samples using the genomic DNA extraction kit (Qiagen) according to the manufacturer's instructions. The entire mitochondrial genomes of the family were PCR amplified in 24 overlapping fragments by using sets of the light strand and the heavy strand oligonucleotide primers, as described elsewhere. Each fragment was purified and subsequently Sanger sequencings were conducted by TSINGKE Biological Technology(Beijing, China). The resultant sequence data were compared with the revised consensus Cambridge sequence (GenBank accession no. NC-012920). His electroencephalogram showed clear increase of 4–5c/s theta waves, 2–3c/s delta waves, with a small amount of sharp waves. His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right (Fig. 1 A). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS (Fig. 1 B). Normal structure and ejection fraction were observed via echocardiography. Serum lactate dehydrogenase, creatine kinase, α-hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range. Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation (Fig. 2 ). The patient was treated according to the diagnosis of mitochondrial encephalomyopathy. Intravenous acyclovir, ceftriaxone and dexamethasone were used for antiviral, antimicrobial, and anti-inflammatory therapy, respectively. Intravenous mannitol was gradually tapered for reducing intracranial pressure with furosemide for inducing diuresis. Intravenous arginine could help to treat alkalosis and supple some essential amino acids. Oral oxiracetam capsules, vitamin B1, and coenzyme Q10 were used for providing nutrition and improving energy. His medications were 30 mg vitamin B1, 0.1gm vitamin C and mecobalamin 750 μg daily after discharge from our hospital. The patient was able to walk and talk slowly with improved writing skills and no stroke-like episodes. The neurological examination was negative and muscle tension was identified as grade V.\", 'Patient concerns:': \"A 12-year-old boy was admitted to Shaoxing People's Hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after treatment of unexplained fever and somnolence.\"}", "questions": ["Which intravenous agent was administered to provide metabolic or amino‑acid support?", "Which co‑enzyme supplement was prescribed to support mitochondrial energy production?"], "ground_truth_arguments": ["Intravenous arginine", "coenzyme Q10"]}
{"id": "CaseReportBench:train-190", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'2. Case Presentation': 'A 19-year-old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents (cousins). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally. On physical examination, there was diffuse palmoplantar keratoderma ( Figure 1 ). Intraoral examination revealed complete edentulous ridges with normal overlying mucosa. In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X-ray, and skull X-ray were normal. She was subsequently provided with artificial dentures and she was a candidate for mandibular bone graft from her skull and dental implants of lower jaw. Complete blood count and liver function tests were also normal. The patient was informed of the indication, and risks and benefits of fiberoptic nasal intubation under sedation. Preoperatively, after careful intravenous catheter insertion, she was premedicated with intravenous midazolam 1 mg and glycopyrolate 0.2 mg. Topical nasal vasoconstriction was achieved with oxymetazolin nasal drop and xylocaine spray 10% in both nostrils. Nasal oxygenation through the nasopharyngeal airway with 100% oxygen was started 3 minutes before the nasal intubation. The patient received a loading dose of dexmedetomidine (Precedex) 1 µg/kg infused over 10 minutes, followed by maintenance dose of Precedex (0.4 µg/kg/h). Gently, she was intubated by fiberoptic. During the awake nasal intubation, the patient’s SpO 2 remained between 97% and 100%. The heart rate varied from 82 to 96 beat/min. Fentanyl (1.5 µg/kg), propofol (2 mg/kg), and cisatracurium (0.15 mg/kg) were used for induction, and general anesthesia was maintained with Sevoflurane, 50% oxygen and 50% nitro oxide. Vital signs were stable during the surgery. Fentanyl (50 µg) and cisatracurium (2 mg) were repeated every 45 minutes. At the end of the surgery, the patient was extubated when she was fully awake and shifted to post anesthesia care unit (PACU) and had a recovery without any complication. Informed consent was taken from the patient regarding the publication of information in the journal. The patient reviewed the case and gave written permission for the authors to publish the report.', 'Case Presentation': 'We report a 19-year-old girl with palmoplantar hyperkeratosis who presented total loss of her teeth. She was candidate to mandibular bone graft and lower jaw dental implants under general anesthesia.'}", "questions": ["Which clinical findings support the diagnosis of Papillon‑Lefèvre syndrome in this patient?"], "ground_truth_arguments": ["characteristic criteria for PLS"]}
{"id": "CaseReportBench:train-358", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["What cytogenetic findings were reported for the patient in the initial karyotype analysis?", "Which endocrine hormone measurements were reported for the patient, and were they within normal reference ranges?", "What were the key findings of the transvaginal ultrasound regarding uterine and ovarian appearance?", "Which endocrine laboratory results (fasting glucose, FSH, LH, TSH, prolactin) were reported as within normal limits?", "What were the results of the repeat karyotype analysis performed at the authors’ genetics laboratory?", "After the repeat karyotype, which hormone levels were described as normal and which remained elevated?", "What were the findings of the ACTH stimulation test for 17‑hydroxyprogesterone, and how were they interpreted?"], "ground_truth_arguments": ["Her karyotype was reported as 45, X{20}/46, XX{80 },", "17 - hydroxy progesterone ( 17 - OHP ) level was 1.3 ng / ml ( 0.2–1.4 ng / ml ), cortisol ( AM ) was 5–6 μg / dl ( 3.7–9.5 μg / dl ) dehydroepiandrosterone sulfate ( DHEAS ) was 189.6 μg / dl ( 65–380 μg / dl ) and serum total testosterone was 318 μg / dl ( 20–130 μg / dl ) which was highly raised", "transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count", "Her fasting glucose, follicle stimulating hormone ( FSH ), luteinizing hormone ( LH ), thyroid stimulating hormone, and prolactin levels were within normal limits", "karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX", "normal levels of 17 - OHP, Cortisol, FSH, LH, but increased levels of testosterone", "adrenocorticotropic hormone ( ACTH ) stimulation test was done, which showed basal plasma 17 - OHP as 2300 ng / dl and postsynacthen ( 60 min ) as 3400 ng / dl ( < 900 ng / dl )"]}
{"id": "CaseReportBench:train-292", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}", "questions": ["What is the patient's age?"], "ground_truth_arguments": ["28 - year - old"]}
{"id": "CaseReportBench:train-93", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 3-year-old boy was admitted to our emergency department because of convulsions and unconsciousness. He had been diagnosed as 21-hydroxylase deficiency at birth. He had been taking oral steroid (hydrocortisone) replacement therapy since then. His parents had stopped steroid therapy without the knowledge of the physician 3 days before the symptoms started. They were admitted to our hospital 6 hours after the onset of the symptoms. He was in coma and had seizures on admission. Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg/dl and white blood cell (WBC) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies. Intravenous hydrocortisone treatment was initiated. Electroencephalography showed focal epileptic activity. Routine brain MRI was performed. Diffusion weighted images (DWI) and susceptibility weighted images (SWI) were also obtained in order to detect ischemia and hemorrhage. T2-weighted and fluid attenuated inversion recovery (FLAIR) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical-subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical-subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient (ADC) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto-occiptal cortical-subcortical regions due to hypoxia and hypoglisemia. We obtained follow-up brain MRI on fifth, twelfth, and twentieth days once the treatment has started. DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae.'}", "questions": ["What demographic information and presenting symptoms are described for the patient upon admission to the emergency department?"], "ground_truth_arguments": ["A 3 - year - old boy was admitted to our emergency department because of convulsions and unconsciousness"]}
{"id": "CaseReportBench:train-411", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'CASE PRESENTATION': \"Following the complaints of other players over a 14 - year old girl with male phenotype in the under 16 age- group of women's national soccer team, further evaluation about her condition was performed by the team physician. In her general appearance, she had hirsutism, increased muscle bulk, dark skin, voice deepening and short stature. In her physical examination her specifications were as below: height: 145 cm, weight: 46 Kg, body mass index (BMI): 21.8, Tanner staging: 1 ( Fig. 1 ), lack of menstrual period, clitoral enlargement, good strength and excessive fatigue after exercise. In her past medical history, following her family's concern about her ambiguous genitalia, she underwent a number of specific laboratory tests and chromosomal karyotype and based on hormonal assessment the final diagnosis was Congenital Adrenal Hyperplasia (C.A.H) due to 21 hydroxylase deficiency. Afterwards, she had undergone surgery (vaginoplasty) when she was 3 years old and also she had been admitted in hospital 2 times because of electrolytes imbalance. In her drug history, she had been using 30 mg hydrocortisone daily in three divided doses (15.8 mg/m 2 ·d) plus 100 mg fludrocortisone daily in 2 divided doses, but recently her drug doses had been changed to 7/5 mg prednisolone in the morning and 5 mg at night. In her sports career, she used to be in First Division League of indoor soccer for 4 years and she was also selected in preparation training camp of women football team for Singapore's youth Olympic Games. She plays as a striker. She is a speedy player with a high level of technique. Despite her impressive role in the team, she usually cannot play more than one halftime because of excessive fatigue and vomiting due to electrolytes imbalance. As her karyotype was XX, based on the IOC (International Olympic Committee) rules, there was no limitation for her participation in international competitions of women. However, following consultations with the TUE (Therapeutic Use Exemption) Committee of games organization, she received TUE to use corticosteroid only within the games period. Now, mainly because of some problems in her medical conditions including prolonged dysfunction due to her ankle sprain, she is playing in the Second Division League of indoor soccer. Because of her irregular check-ups, there isn't much laboratory tests available. Her most recent one, requested by the team physician is shown in the Table 1 .\", 'Case Presentation': \"The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia. She plays in the women's national soccer team of under 16. She has been in the first division league of indoor soccer for 4 years and was also selected in the preparation training camp of women's football team for Singapore's youth Olympic Games. Her illness and dependence on corticosteroid have caused some concerns for her participation in the international competitions of women. However, following consultations with the Therapeutic Use Exemption (TUE) Committee of games organization, she received TUE to use corticosteroid only within the games period. Despite all her problems, she is now playing in the Second Division League of indoor soccer.\"}", "questions": ["What are the patient's height, weight, and body mass index (BMI)?", "What is the patient's Tanner stage?"], "ground_truth_arguments": ["height : 145 cm, weight : 46 Kg, body mass index ( BMI ): 21.8, Tanner staging : 1"]}
{"id": "CaseReportBench:train-240", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': \"A 16-year-old Iraqi boy, born of first-cousin parents, presented to our outpatient clinic at Al-Sadr Teaching Hospital with hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing. He also had hearing loss, speaking difficulties, premature graying of the hair, gynecomastia, corneal arcus, hypospadias, and finger and toe deformities (hallux valgus). These features started at age 10, except for the hypospadias, which was present since birth, and the hearing loss and speaking difficulties, which were diagnosed in early childhood. The mother stated that the child delayed walking until the age of 2 years, and she reported that he had a severe ear infection by the age of 6. The patient has 3 brothers and 2 sisters; his older brother has bilateral swelling of the feet and deformities of the toes, but the patient's other siblings are all healthy. See Table I for clinical examination findings ( Fig 1, Fig 2, Fig 3 ). Table I Findings on examination Examination Findings Vital signs Pulse rate, 83 beats per minute; blood pressure, 100/70 mmHg; respiratory rate, 13 breaths per minute; and temperature, 37°C Anthropometric parameters Weight, 47.1 kg; height, 160 cm; MUAC, 19.3; BMI, 18.4; height/age, -1.7 SD; BMI/age, -0.9 SD Skin Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well-demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees (see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt-and-pepper gray hair (see Fig 2 ) Head OFC, 51 cm (-2.8 SD, <1 st percentile); face looks flat; ears are of abnormal shape and size. Eyes Bilateral corneal arcus; moderate exophthalmos; asymmetrical corneal light reflex. Ophthalmoscopic examination showed bilateral swelling of the optic disc. Visual acuity is normal. Hearing assessment Severe hearing loss Breast Bilateral gynecomastia Heart Normal Abdomen Mild hepatosplenomegaly Lymph nodes Severely enlarged inguinal lymph nodes, with tenderness on palpation Genitourinary Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal. Musculoskeletal Bilateral hallux valgus deformity, with fixed flexion contractures, in the interphalangeal joints of the toes and the little fingers (see Fig 3 ). There is also a nonpitting edema of the ankles. BMI, Body mass index; MUAC, mid-upper arm circumference; OFC, occipitofrontal circumference. Fig 1 Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees. Fig 2 Posterior view of the patient's head shows salt-and-pepper gray hair. Fig 3 Hallux valgus deformity, with flexion contractures of the toes and little fingers. Laboratory test results showed elevated erythrocyte sedimentation rate of 93 (normal range, 0–15 mm/h), elevated serum cortisol of 1030 nmol/L (normal range at morning, 171-536 nmol/L), and decreased serum testosterone level of 2.63 ng/mL (normal range, 2.8-8 ng/mL). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti–double-stranded DNA, anti-cyclic citrullinated peptide, and lipid profile all were normal. Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal, and pure tone audiometry found bilateral profound mixed hearing loss. Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes (see Fig 4 ). The biopsy was taken from the hyperpigmented patch on the medial aspect of the right thigh. Fig 4 Immunohistochemistry stain shows diffuse infiltration of histiocytes. (CD68 + ; original magnification: ×400.)\"}", "questions": ["What laboratory abnormalities were reported, including erythrocyte sedimentation rate, serum cortisol, serum testosterone, complete blood count, and the results of thyroid, liver, renal, electrolyte, vitamin B12, iron studies, autoantibody panels, and lipid profile?", "What were the findings of the cardiac evaluations (echocardiography and electrocardiogram), abdominal ultrasound, and brain magnetic resonance imaging?", "What histopathological features were observed in the skin biopsy, specifically regarding fibrosis, collagen bundle thickness, and the presence of CD68‑positive histiocytes?", "What did immunohistochemical staining of the biopsy reveal about histiocyte infiltration?"], "ground_truth_arguments": ["elevated erythrocyte sedimentation rate of 93 ( normal range, 0–15 mm / h ), elevated serum cortisol of 1030 nmol / L ( normal range at morning, 171 - 536 nmol / L ), and decreased serum testosterone level of 2.63 ng / mL ( normal range, 2.8 - 8 ng / mL ). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti – double - stranded DNA, anti - cyclic citrullinated peptide, and lipid profile all were normal", "Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal", "Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes", "Immunohistochemistry stain shows diffuse infiltration of histiocytes"]}
{"id": "CaseReportBench:train-580", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Presentation of case': 'The case was a 65-year-old female with VDRR who reported progressive weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm. Imaging studies demonstrated cord compression with ectopic ossification at the rim of the occipital bone and OPLL at C1 level. Ankylosis of the whole spine below the C2 vertebra was also noted with preserved mobility only at the craniovertebral junction. The patient was first referred to our hospital because of difficulty in walking at the age of 34, when she was diagnosed with VDDR. Later, the diagnosis was genetically confirmed as described by a different research group . The patient had previously undergone T7–T9 laminectomy due to thoracic myelopathy at another hospital at the age of 24, after which her myelopathic symptoms subsided for 7 years. At the age of 34, she underwent a second posterior decompression surgery (T4–T9) for gait disturbance due to thoracic myelopathy after a diagnosis of OPLL and OYL, which resulted in improvement of her symptoms. Since then, the patient has been followed-up on annual basis and remained functionally stable for over 30 years. At the age of 65, she reported weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm. She was admitted for further investigation and treatment. On admission, she was 118 cm tall with a marked round back and bowed legs. She was able to walk only short distances supporting herself on a wall. Neurologic examination revealed decreased light touch and pinprick sensation, and motor weakness (3/5 strength) in the distal upper extremities. The grip power was 6 kg in both hands. Tendon reflexes were equivocal with indifferent Babinski sign bilaterally. Plain radiograph showed marked kyphosis of the thoracic spine (T1–T12 angle; 94°) ( Fig. 1 ). Computed tomography demonstrated ankylosis of the whole spine below the C2 vertebra with extensive ossification of the paraspinal ligaments ( Fig. 2 A, B). In contrast, decreased but preserved mobility (9° on flexion and extension) was noted at the craniovertebral junction (CVJ). No overt radiographic instability was found in the atlantoaxial region, with an atlantodental interval of 1 mm. In addition, there was ossification at the rim of the occipital bone, and OPLL at the C1 level. Magnetic resonance imaging (MRI) revealed spinal cord compression at the levels of both the occipital bone and C1 ( Fig. 3 ). The patient underwent posterior decompression, in which the posterior arch of C1 and the ossified rim of the occipital bone were resected. Deformation of the dural sac was observed at locations corresponding to the resected portions of the rim of the occipital bone and C1 posterior arch, indicating that there had been sustained pressure on the sac. Her postoperative course was uneventful. At the 18-month follow-up visit, the patient was free of pain and numbness. Her grip power had improved to 20 kg in the right and 15 kg in the left hand. She had regained the ability to walk with the support of a cane.', 'Patient consent': 'Informed consent was obtained from all individual participants included in this study.'}", "questions": ["What age group does the patient fall into at presentation?"], "ground_truth_arguments": ["65 - year - old"]}
{"id": "CaseReportBench:train-353", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 12-year-old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days. On physical examination the child was found to have retarded growth (dwarfism) and a pendulous abdomen. Per abdominal examination revealed hepatomegaly. USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm–sized, well-defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well-circumscribed, low-attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted. Hepatomegaly with diffusely low attenuation of liver, bilateral renal calculi (which hinted at hyperuricemia – a known feature of von Gierke disease), clinical features of dwarfism, facial dysmorphism, and protuberant abdomen, were all features that favored the diagnosis of von Gierke disease. Moreover, in the pediatric age-group, liver tumors are rare and hepatic adenoma occurs almost exclusively in patients with underlying von Gierke disease. CT scan features like well-circumscribed margins, subcapsular location, and contrast enhancement also supported the diagnosis of hepatic adenoma. Based on these CT scan findings and clinical features, a probable diagnosis of hepatic adenoma in a case of type Ia glycogen storage disease (von Gierke disease) was suggested. Preoperative laboratory evaluation revealed increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits. The patient was operated and the mass in the liver was surgically resected. The specimen was sent for histopathological examination along with a small bit of liver tissue, which showed PAS-positive glycogen-rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma.'}", "questions": ["What ultrasound and CT imaging findings were reported for the liver, including lesion size, location, characteristics, and any renal abnormalities?", "Which laboratory results were abnormal, specifically regarding uric acid, cholesterol, random blood glucose level, and liver function tests?", "What did the histopathological examination of the liver tissue and the hepatic lesion demonstrate, including staining results and final diagnosis?"], "ground_truth_arguments": ["USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm – sized, well - defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well - circumscribed, low - attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted.", "increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits", "histopathological examination along with a small bit of liver tissue, which showed PAS - positive glycogen - rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma."]}
{"id": "CaseReportBench:train-44", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Description': 'The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like “X”-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS).', 'Case presentation': 'A 32-year-old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient’s visit to our hospital. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Oral informed consent was obtained from the patient. On the patient’s maternal side, there was a history of rectal cancer (the patient’s grandmother, an uncle, and an aunt), uterine cancer (a 29-year-old female cousin), rectal cancer with uterine cancer (two aunts), and colon polyposis (a 29-year-old male cousin) ( Figure 1A ). A physical examination showed mild tenderness only in the right lower abdomen. No significant abnormalities were found in serum tumor markers. A colonoscopy revealed a cauliflower-like mass at the beginning of the ascending colon ( Figure 1B ). Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast-enhanced computed tomography (CT) showed ascending colon cancer with intussusception ( Figure 1D ). The preoperative diagnosis was cT3N0M0 colon cancer, according to the TNM classification. On August 27, 2021, the patient underwent laparoscopic radical right hemicolectomy under general anesthesia. During the operation, we found that there were two ICAs derived from the SMA, with the ileocolic vein (ICV) crossing anterior to the SMA ( Figure 2A ). The right colic vein was also absent ( Figure 2B ). The gastrocolic trunk of Henle was draining into the superior mesenteric vein (SMV), which was joined by the right gastroepiploic and colic veins, the anterior superior pancreaticoduodenal vein, and the superior right colic vein ( Figure 2C ). Furthermore, the SMA and SMV were found to be accompanied like “X”-shaped variant ( Figure 2D ). As we saw in the surgery，abdominal contrast-enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery (RCA) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C ). We summarized the schematic diagram of vascular variation of this patient ( Figure 3D ). The patient was discharged on the fourth day after surgery. Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient’s tumor sample ( Figure 5C,5D ). Given the patient’s family history of cancer, we highly suspected Lynch syndrome (LS). Next-generation sequencing (NGS), performed by 3D Medicines Inc. (Shanghai, China), was used to analyze tumor and blood samples from the patient. As shown in Figure 6, the results revealed MLH1 c.885-1_893del, which may represent a change in the conformation of the acceptor splicing site, which may have impeded mRNA formation, eventually leading to deficient mismatch repair. Seven weeks after surgery, the patient was administered a regimen of adjuvant chemotherapy with CapeOX (day 1, oxaliplatin 130 mg/m 2, day 1 to 14 capecitabine 1,000 mg/m 2, po, twice a day, every 3 weeks) for four cycles. Four months after the end of chemotherapy, CT reexamination showed no tumor recurrence ( Figure 7 ).'}", "questions": ["What symptoms did the patient report at presentation, including their duration and any symptoms that were explicitly denied?", "What hospital, department, and admission date are reported for the patient’s initial presentation?", "Summarize the mother’s cancer history as described, including cancer types, years of surgery, and current disease status.", "What cancer types were reported for each maternal‑side relative, and which family members were affected?", "In what way did the clinicians consider the patient’s family history of cancer when forming the diagnostic or management plan, and which organ types were highlighted?", "What surgical procedure was performed for the colon cancer and what type of anesthesia was used, without mentioning the date?"], "ground_truth_arguments": ["The patient was a 32 - year - old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms.", "she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital", "Given the patient ’s family history of colon and uterine cancer", "A 32 - year - old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient ’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient ’s visit to our hospital", "On the patient ’s maternal side, there was a history of rectal cancer ( the patient ’s grandmother, an uncle, and an aunt ), uterine cancer ( a 29 - year - old female cousin ), rectal cancer with uterine cancer ( two aunts ), and colon polyposis ( a 29 - year - old male cousin )", "Given the patient ’s family history of cancer"]}
{"id": "CaseReportBench:train-15", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case presentation': 'We report a case of a 40-year-old man with CAH/21-hydroxylase deficiency, who willingly interrupted Prednisolone therapy for years. In 2007 his left adrenal gland was removed and diagnosed with adrenocortical carcinoma. In 2012 CT scan ( Fig. 1 ) showed a tumor in the right adrenal gland, confirmed in 2013 by MRI, with retroperitoneal lymphadenomegaly. Serum hormonal screening showed high 17-OH progesterone and ACTH. The patient refused operation. He was referred to us from another hospital because of a synchronous progressive enlargement of bilateral testicular masses during substitutive medical therapy ( Fig. 2 ). Serum tumor markers at 12.09.2013: AFP 10.56 IU/mL (AFP 4.03 IU/mL 01.2012), hGT beta and CEA – not elevated, semen analyses: azoospermia. Considering the possibility of malignant testicular neoplasm, the patient underwent bilateral orchiectomy, because the frozen sections were interpreted as malignant tumors. Gross findings: right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds (0.1–1.5 cm). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin-α were positive in 50% of the cells. There were no mitotic figures on HE-staining (Ki 67 negative). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated. We excluded primary germ cell testicular tumors and anaplastic large cell lymphoma, metastatic nonsecreting pheochromocytoma. “TARTs” was the appropriate diagnosis. There was still suspicion for metastatic adrenocortical carcinoma because of the CT and MRI findings. In order to prove the diagnosis the patient agreed to the surgical removal of his right adrenal gland in 01.2014. Adrenocortical carcinoma was histologically diagnosed again at other hospital. We revised all slides and performed immunohistochemical analyses. In the left adrenal gland we found polygonal cells with mild nuclear pleomorphism, conspicuous nucleoli, abundant eosinophilic granular cytoplasm, some with lipochrome pigments, without mitotic activity (Ki 67 positive in <1% of nuclei). The clear cell component was about 26%. In CAH, marked diffuse hyperplasia of zona fasciculata is a result of ACTH stimulation. There is also a conversion of zona fasciculata cells into zona reticularis-type cells (lipid-depleted). The cells exhibited strong positive expression for vimentin, Melan A and inhibin. In the right adrenal gland microscopically we found fields and circumscribed but nonencapsulated nodules that protruded into the adjacent fat, consisting of fasciculata-type cells and nodules composed of zona reticularis-type cells with lipofuscin. Nuclear and cellular pleomorphism was more prominent than in the left adrenal gland. Mitoses necrosis, hemorrhage, sinusoidal, vascular and capsular invasion were not found. The required number of morphological criteria, according to Weiss and Aubert, to classify the lesion as carcinoma, were not met. 2 Revised diagnosis: CAH bilateral adrenal cortical hyperplasia of a diffuse and nodular type with multiple bilateral cortical nodules, pigmented nodules and congenital adrenal cytomegaly and bilateral TARTs revealing morphologically similar changes.'}", "questions": ["Describe the macroscopic characteristics of the testicular masses, including any notable size ranges and appearance.", "What did the frozen‑section analysis conclude about the nature of the testicular tumors?", "What microscopic histopathological features were identified in the testicular tissue, including cellular morphology, immunohistochemical profile (e.g., CD117, PLAP, CK, Melan A, inhibin‑α, Ki‑67), and evidence of vascular or cord invasion?", "What were the findings of the semen analysis performed on the patient?"], "ground_truth_arguments": ["bilateral testicular masses", "semen analyses : azoospermia", "frozen sections were interpreted as malignant tumors. Gross findings : right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds ( 0.1–1.5 cm ). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin - α were positive in 50 % of the cells. There were no mitotic figures on HE - staining ( Ki 67 negative ). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated."]}
{"id": "CaseReportBench:train-425", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case report': 'SH is a 44-year-old female diagnosed with mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure. After her diagnosis was made, she was initially followed by Neurology; however she was subsequently referred to our cardiomyopathy clinic secondary to progressive left ventricular hypertrophy (LVH) on echocardiogram and the known association between MELAS and cardiac disease. Prior to evaluation by our clinic, she had a clinical diagnosis of MELAS but evaluation by our cardiovascular genetics team yielded positive results for the A-to-G transition at nucleotide 3243 (m.3243A > G) of the mitochondrial genome, with 25% heteroplasmic deleterious mutation in MT-TL1, a mitochondrial leucine transfer RNA gene, the most common mutation underlying MELAS. At the time of presentation to our clinic, SH had carried the diagnosis of MELAS for 11 years and her symptoms had progressed significantly so that she was no longer able to be employed and her husband became her primary caretaker. Her clinical status included multiple medical problems related to her MELAS diagnosis: sensorineural hearing loss, myopathy, bilateral ophthalmoplegia, ptosis, seizures and stroke-like episodes with concern for dementia. Her family history is significant for a 12-year-old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss. In addition to a clinical exam and genetic evaluation, cardiac work-up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non-sustained atrial tachycardia ( Fig. 1 ). From a cardiac imaging perspective, an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub-epicardium of approximately 25–50% in thickness in the inferior segment at the base, inferior to lateral segments at the mid-ventricle and lateral segment of the apex, with sparing of the endocardium and septum ( Fig. 1 A and 1 B). Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes (R > L), and moderate cerebellar atrophy with extensive white matter disease. Monitoring laboratory evaluation yielded no significant abnormalities with the exception of a slightly elevated brain natriuretic peptide of 305 (normal < 200 ng/L). Her liver and kidney functions were normal and there was no hyperglycemia. From a cardiac management perspective, she has been maintained on Atenolol 25 mg twice daily and aspirin 325 mg once daily.'}", "questions": ["What left ventricular structural changes were identified on echocardiography, including any progression and systolic function status?", "What arrhythmic abnormalities were reported on the patient's electrocardiogram and Holter monitor?", "What patterns of late gadolinium enhancement were observed on cardiac MRI, including location, extent, and myocardial layers involved?", "How did the patient's brain natriuretic peptide level compare to the normal reference range?"], "ground_truth_arguments": ["progressive left ventricular hypertrophy ( LVH ) on echocardiogram", "cardiac work - up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non - sustained atrial tachycardia", "an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub - epicardium of approximately 25–50 % in thickness in the inferior segment at the base, inferior to lateral segments at the mid - ventricle and lateral segment of the apex, with sparing of the endocardium and septum", "slightly elevated brain natriuretic peptide of 305 ( normal < 200 ng / L )."]}
{"id": "CaseReportBench:train-232", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': \"The patient was a 37-year-old female, of 157 cm in height and 45 kg in weight. She was transferred to our department from a local hospital due to psychiatric features (both agitated behavior and auditory hallucinations), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic-clonic seizures. She had a long history of episodic migraine-like headaches and progressive bilateral hearing loss for 3 years. However, she did not take any medication. Her vital signs showed a normal body temperature of 36.8 °C, a hypotension of 90/56 mm Hg and pulse at 72 beats per minute. Because of the patient's psychiatric symptoms and application of sedative after seizure attacks, she could not cooperate with physical examination. The laboratory data showed high anion gap metabolic acidosis with elevated levels of lactate and pyruvate. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were decreased. Her TSH level was low at 0.26 mU/L (normal range 0.35–5.5 mU/L), and FT4 concentration was 7.56 pmol/L (normal range 10.2–31 pmol/L). Both serum free and total triiodothyronine (FT3 and TT3) were significantly lower than normal range. FT3 concentration was 2.28 pmol/L (normal range 3.5–6.5 pmol/L), and TT3 concentration was 0.6 nmol/L (normal range 1.2–3.4 nmol/L). Moreover, elevated titers of serum anti-thyroglobulin and anti-thyroid microsomal antibodies were detected. Cerebral spinal fluid (CSF) studies were normal for cell counts and biochemistry, and negative for culture. CSF IgG index was 0.48 (normal range ≤ 0.7), and oligoclonal bands (OB) was negative. Computed tomography (CT) scan showed lesions of hypodense in the left temporal and parietal lobe, with brainstem and cerebellar atrophy ( Fig. 1 A). No evidence of subarachnoid or intracerebral hemorrhage. Vascular imaging of the cervical and cerebral arteries by CT angiography excluded the possibility of cerebrovascular disease ( Fig. 1 B). However, CT images were not conclusive to differentiate between the infectious or metabolic lesion. On day 5, brain magnetic resonance imaging MRI (3.0 T) revealed a hypointensity lesion in the left temporal-parietal lobe on T1 weighted image ( Fig. 2 A), and increased signal intensity in the same region on FLAIR sequences ( Fig. 2 B) with a clearly restricted diffusion ( Fig. 2 C). The signal intensity on ADC sequence was mildly reduced ( Fig. 2 D). No obvious enhancement was found on Gd-DTPA enhanced images ( Fig. 2 E). MR spectroscopy was carried out as well. Compared to the ipsilateral normally appearing area ( Fig. 2 F), there was a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) with decreased NAA spectrum and reduced NAA/Cr ratio ( Fig. 2 G). The change of the spectrum reflected the severity of metabolic disorders, suggesting the local accumulation of lactic acid and disturbance of hypoxic processes. Fig. 1 CT scan showed lesions of hypodense in the left temporal and parietal lobe (Panel A). Three-dimensional reconstruction of CT vessel images (Panel B). Fig. 1 Fig. 2 Brain MRI (3.0 T) revealed a hypointense lesion in the left temporal and parietal lobe on T1 (Panel A), and increased signal intensity in the same region on Flair (Panel A) image with a clearly restricted diffusion (Panel C). The signal intensity on ADC sequence is mildly reduced (Panel D). No obvious enhancement was found on Gd-DTPA enhanced images (Panel E). Compared to the ipsilateral normally appearing area (Panel F), MR spectroscopy presented a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) (Panel G). Panels f and g are the molecular findings of metabolites respectively. Fig. 2 An electroencephalogram was performed on day 7 and displayed bilateral slow wave activities. Brainstem auditory evoked potential (BAEP) showed the bilateral sensorineural hearing loss. All the clinical and radiological findings were suggestive of mitochondrial disease. The final diagnosis of MELAS syndrome was confirmed by genetic analysis. The patient's peripheral blood leukocytes was detected by restriction fragment length polymorphism (RFLP) and revealed a mitochondrial DNA (mtDNA) mutation at A3242G point ( Fig. 3 ). Fig. 3 Mitochondrial DNA (mtDNA) mutation at A3242G point. Fig. 3 Her medications included L-arginine, phenobarbital, co-enzyme Q and levothyroxine substitution therapy. The patient's condition continuously improved, and was discharged on day 23. Six months following discharge, this patient had no further seizure.\"}", "questions": ["What metabolic abnormalities were present, including anion gap status and serum lactate and pyruvate levels?", "Which thyroid function tests were abnormal and what was the direction of the abnormality (elevated or decreased) for each?", "What thyroid autoantibodies were detected and were their titers elevated?", "What were the cerebrospinal fluid findings: cell count, biochemistry, IgG index, and oligoclonal band status?", "What did the CT scan show regarding brain parenchymal lesions, brainstem/cerebellar atrophy, hemorrhage, and vascular imaging results?", "What MRI characteristics were observed in the left temporal‑parietal lesion on T1, FLAIR, diffusion‑weighted imaging, ADC, and post‑contrast sequences?", "What metabolic information was revealed by MR spectroscopy of the lesion (e.g., lactate peak, NAA levels, NAA/Cr ratio)?", "Was a mitochondrial DNA mutation identified, and if so, what general type of mutation was reported?"], "ground_truth_arguments": ["high anion gap metabolic acidosis with elevated levels of lactate and pyruvate. Serum levels of thyroid - stimulating hormone ( TSH ) and free thyroxine ( FT4 ) were decreased. Her TSH level was low at 0.26 mU / L ( normal range 0.35–5.5 mU / L ), and FT4 concentration was 7.56 pmol / L ( normal range 10.2–31 pmol / L ). Both serum free and total triiodothyronine ( FT3 and TT3 ) were significantly lower than normal range. FT3 concentration was 2.28 pmol / L ( normal range 3.5–6.5 pmol / L ), and TT3 concentration was 0.6 nmol / L ( normal range 1.2–3.4 nmol / L ). Moreover, elevated titers of serum anti - thyroglobulin and anti - thyroid microsomal antibodies were detected. Cerebral spinal fluid ( CSF ) studies were normal for cell counts and biochemistry, and negative for culture. CSF IgG index was 0.48 ( normal range ≤ 0.7 ), and oligoclonal bands ( OB ) was negative. Computed tomography ( CT ) scan showed lesions of hypodense in the left temporal and parietal lobe, with brainstem and cerebellar atrophy ( Fig. 1 A ). No evidence of subarachnoid or intracerebral hemorrhage. Vascular imaging of the cervical and cerebral arteries by CT angiography excluded the possibility of cerebrovascular disease ( Fig. 1 B ). However, CT images were not conclusive to differentiate between the infectious or metabolic lesion. On day 5, brain magnetic resonance imaging MRI ( 3.0 T ) revealed a hypointensity lesion in the left temporal - parietal lobe on T1 weighted image ( Fig. 2 A ), and increased signal intensity in the same region on FLAIR sequences ( Fig. 2 B ) with a clearly restricted diffusion ( Fig. 2 C ). The signal intensity on ADC sequence was mildly reduced ( Fig. 2 D ). No obvious enhancement was found on Gd - DTPA enhanced images ( Fig. 2 E ). MR spectroscopy was carried out as well. Compared to the ipsilateral normally appearing area ( Fig. 2 F ), there was a significantly elevated lactate peak at 1.3 ppm in region of interest ( ROI ) with decreased NAA spectrum and reduced NAA / Cr ratio ( Fig. 2 G ). The change of the spectrum reflected the severity of metabolic disorders, suggesting the local accumulation of lactic acid and disturbance of hypoxic processes. Fig. 1 CT scan showed lesions of hypodense in the left temporal and parietal lobe ( Panel A ). Three - dimensional reconstruction of CT vessel images ( Panel B ). Fig. 1 Fig. 2 Brain MRI ( 3.0 T ) revealed a hypointense lesion in the left temporal and parietal lobe on T1 ( Panel A ), and increased signal intensity in the same region on Flair ( Panel A ) image with a clearly restricted diffusion ( Panel C ). The signal intensity on ADC sequence is mildly reduced ( Panel D ). No obvious enhancement was found on Gd - DTPA enhanced images ( Panel E ). Compared to the ipsilateral normally appearing area ( Panel F ), MR spectroscopy presented a significantly elevated lactate peak at 1.3 ppm in region of interest ( ROI )", "mitochondrial DNA ( mtDNA ) mutation at A3242 G point"]}
{"id": "CaseReportBench:train-118", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 5 year-old boy was referred to the Pediatric Dentistry Clinic with the complaint of \"a small ball that appeared in the mouth\". During the anamnesis, the patient was diagnosed as having hypophosphatemic vitamin D-resistant rickets. The child was the third twin; however, the parents as well as the siblings, did not have the metabolic disorder. The medicines taken by the patient were calcitriol and phosphate supplements. He presented short stature and several skeletal abnormalities. Clinical examinations revealed fistula at the periapical region of primary maxillary left lateral incisor without caries or trauma ( Figure 1 ). The patient presented complete primary dentition and none of the teeth examined showed evidence of caries ( Figure 2A-B ). Radiographic examinations included periapical, panoramic and occlusal views showing pulp chambers enlarged, with pulp horns extending to the dentino-enamel junction, poorly defined lamina dura and hypoplastic alveolar ridge ( Figure 2C ). The patient presented a large physiologic wear of the incisors, geographic tongue and primary mandibular right lateral incisor (#82) and canine (#83) with crown alteration ( Figure 3A-B ). There were areas of rarefaction around the apices of the primary maxillary right and left central incisor (#51,61), primary maxillary right and left lateral incisor (#52,62), primary maxillary right and left canine (#53,63) and primary maxillary right and left first molar (#54,64), primary mandibular right and left central incisor (#81,71) ( Figure 4 and 5A-B ). Initially, two sections of management were performed. The treatment was divided into two phases: at first, the extraction of the teeth was performed: #51, 61, 81 and 71. At the second phase, endodontic treatment of the teeth: #52, 62, 53 and 63. These procedures were executed with local anesthesia and rubber dam isolation. The root canals were submitted to preparation with Kerr files and dressing with paramonoclorofenol (Biodinâmica LTDA, Brazil) for 48 hours. Canals were filled with zinc oxid-eugenol and iodoform paste and restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA). During the aforementioned treatment, primary mandibular right first molar (#84), primary maxillary right and left first molar (#54,64) and primary mandibular left second molar (#75) showed periapical fistula without evidence of caries or trauma in a short-term. These teeth were extracted. However, the child was constantly sick and did not attend the consultations. In the other teeth, the primary mandibular right second molar (#85), lateral incisor and canine (#82,83), primary maxillary right and left second molars (#55,65), primary mandibular left first molar and lateral incisor and canine (#74,73,72), the choice of treatment was to open the pulp chambers and make a dressing with formocresol (Biodinâmica LTDA, Brazil). After a 7-day period, the dressing with formocresol was removed and the root instrumentation was performed and filled with zinc oxid-eugenol and iodoform paste, afterwards the teeth were restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA) ( Figure 6 ). In order to maintain the space of primary maxillary right and left second molars and primary mandibular right second molar, a fixed space-maintainer was made and cemented with resin modified glass ionomer cement (Rely X, 3M/ESPE, USA) ( Figure 7A-B ). The postoperative clinic course was uneventful and after six months of follow-up, the child did not show clinical abscesses.'}", "questions": ["What radiographic techniques were employed in the patient's examination?", "What abnormalities were observed in the pulp chambers on the radiographs?", "How were the pulp horns described in relation to the dentino‑enamel junction in the imaging findings?", "What description was given for the lamina dura in the radiographic assessment?", "What observations were reported regarding the alveolar ridge on the radiographs?"], "ground_truth_arguments": ["Radiographic examinations included periapical, panoramic and occlusal views showing pulp chambers enlarged, with pulp horns extending to the dentino - enamel junction, poorly defined lamina dura and hypoplastic alveolar ridge"]}
{"id": "CaseReportBench:train-134", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE PRESENTATION': \"Following the complaints of other players over a 14 - year old girl with male phenotype in the under 16 age- group of women's national soccer team, further evaluation about her condition was performed by the team physician. In her general appearance, she had hirsutism, increased muscle bulk, dark skin, voice deepening and short stature. In her physical examination her specifications were as below: height: 145 cm, weight: 46 Kg, body mass index (BMI): 21.8, Tanner staging: 1 ( Fig. 1 ), lack of menstrual period, clitoral enlargement, good strength and excessive fatigue after exercise. In her past medical history, following her family's concern about her ambiguous genitalia, she underwent a number of specific laboratory tests and chromosomal karyotype and based on hormonal assessment the final diagnosis was Congenital Adrenal Hyperplasia (C.A.H) due to 21 hydroxylase deficiency. Afterwards, she had undergone surgery (vaginoplasty) when she was 3 years old and also she had been admitted in hospital 2 times because of electrolytes imbalance. In her drug history, she had been using 30 mg hydrocortisone daily in three divided doses (15.8 mg/m 2 ·d) plus 100 mg fludrocortisone daily in 2 divided doses, but recently her drug doses had been changed to 7/5 mg prednisolone in the morning and 5 mg at night. In her sports career, she used to be in First Division League of indoor soccer for 4 years and she was also selected in preparation training camp of women football team for Singapore's youth Olympic Games. She plays as a striker. She is a speedy player with a high level of technique. Despite her impressive role in the team, she usually cannot play more than one halftime because of excessive fatigue and vomiting due to electrolytes imbalance. As her karyotype was XX, based on the IOC (International Olympic Committee) rules, there was no limitation for her participation in international competitions of women. However, following consultations with the TUE (Therapeutic Use Exemption) Committee of games organization, she received TUE to use corticosteroid only within the games period. Now, mainly because of some problems in her medical conditions including prolonged dysfunction due to her ankle sprain, she is playing in the Second Division League of indoor soccer. Because of her irregular check-ups, there isn't much laboratory tests available. Her most recent one, requested by the team physician is shown in the Table 1 .\", 'Case Presentation': \"The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia. She plays in the women's national soccer team of under 16. She has been in the first division league of indoor soccer for 4 years and was also selected in the preparation training camp of women's football team for Singapore's youth Olympic Games. Her illness and dependence on corticosteroid have caused some concerns for her participation in the international competitions of women. However, following consultations with the Therapeutic Use Exemption (TUE) Committee of games organization, she received TUE to use corticosteroid only within the games period. Despite all her problems, she is now playing in the Second Division League of indoor soccer.\"}", "questions": ["What phenotypic characteristics are described for the patient in relation to typical female development?", "What information is provided regarding the patient's menstrual history and genital examination?", "What details are reported about the patient's genital anatomy in early medical records?"], "ground_truth_arguments": ["girl with male phenotype", ", lack of menstrual period, clitoral enlargement,", "ambiguous genitalia,"]}
{"id": "CaseReportBench:train-164", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory. Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE. Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium. The patient is being followed up and has been specifically instructed to report if she becomes pregnant.'}", "questions": ["What vital sign measurements were documented for the patient?"], "ground_truth_arguments": ["blood pressure and other vital signs were normal"]}
{"id": "CaseReportBench:train-158", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'A 19 year old boy presented with bilateral slow growing and painful swellings of his achilles tendons of 4 year duration. On clinical examination each swelling was of size 5×2 cm, firm, nodular, tender and localized to the distal portion of the tendoachilles just above its insertion point to the calcaneal tuberosity ( Fig. 2 ). He was more symptomatic on the right side. He was initially advised rest, analgesics and foot wear modification. However, the symptoms did not subside and the situation worsened resulting in significant disability with limitation of his walking distance. Initial radiographs of both ankles showed homogenous soft tissue shadow in the lower halves of tendoachilles ( Fig. 3 ). Magnetic resonance imaging showed localized homogenous hyper intense signals with fusiform swellings of tendoachilles ( Fig. 4 ). Surgical excision was offered and the right sided one was selected first as it was more symptomatic. The swollen tendinous portion measuring 6×3 cm was excised ( Fig. 5 ) followed by reconstruction using the ipsilateral peroneus brevis tendon. Immediate and early post-operative period was uneventful. Biopsy of the excised specimen revealed it to be a xanthoma characterized by the accumulation of mononuclear cells with foamy cytoplasm and multinucleated giant cells with high concentration of cholestanol. Thus a diagnosis of cerebro-tendinous xanthomatosis was made. On detailed retrospective inquiry, he had surgery for bilateral juvenile cataracts at the age of 8, along with history of chronic intractable diarrhea. He was coherent and co-operative but slow cerebrated with low intelligence. There were no central nervous system symptoms like convulsions, abnormal gait or incoordination of movements. Family history revealed that he was a child of a consanguineous marriage. Other sibling, a girl was normal. He was short statured measuring 144 cm in height ( Fig. 1 ), thin built with a peculiar yellow conjunctiva. Hematological and biochemical investigations including liver function tests, lipid profile, thyroid function tests and ultrasound examination of abdomen were normal. A special test - serum cholestanol level was elevated to 4.37 mg/dL (normal value: 0.02-0.12 mg/dL). Based on the clinical picture, pathological and serological analysis, the diagnosis of cerebro-tendinous xanthomatosis was confirmed and was kept on medical therapy with chenodeoxycholic acid (CDCA), a synthetic bile acid. RESULT: He was kept under regular follow up with neurologic and neuropsychological evaluation, musculoskeletal examination and serum cholestanol estimation. He started to improve after 3 months of continued medication. According to the latest follow up of 23 months, he achieved complete improvement in his mental status and normal values of serum cholestanol. The pain on the left (non-operated) tendoachilles disappeared completely although swelling persisted. His walking distance improved. However, had reappearance of the swelling in the reconstructed tendon on the right side, although was not painful ( Fig. 6 )', 'Case Report:': 'We find such a rare and perplexing case in a 19 year boy who presented with painful swellings of both achilles tendons causing signification limitation of walking distance. This was initially interpreted as a localized benign disorder and was offered surgical treatment. Excision of the swollen achilles tendon followed by reconstruction using peroneus brevis tendon was done, first on the more symptomatic right side. The diagnosis of cerebrotendinous xanthomatosis was made retrospectively after histopathological as well as biochemical analyses and appropriate medical therapy was initiated.'}", "questions": ["Describe the characteristics of the bilateral Achilles tendon swellings, such as their growth rate, approximate size, consistency, tenderness, typical location, and which side was more symptomatic.", "What impact did the Achilles tendon swellings have on the patient's walking distance and overall functional ability?", "Summarize the radiographic and MRI findings of the Achilles tendons as reported in the case.", "What histopathological features were identified in the excised tendon specimen, including the types of cells present and any notable lipid‑related findings?", "How is the patient's stature described in relation to normal height expectations?", "After surgical excision and subsequent medical therapy, what were the outcomes concerning pain, swelling, and walking distance for the left (non‑operated) and right (reconstructed) Achilles tendons?"], "ground_truth_arguments": ["bilateral slow growing and painful swellings of his achilles tendons", "each swelling was of size 5×2 cm, firm, nodular, tender and localized to the distal portion of the tendoachilles just above its insertion point to the calcaneal tuberosity ( Fig. 2 ). He was more symptomatic on the right side", "significant disability with limitation of his walking distance", "Initial radiographs of both ankles showed homogenous soft tissue shadow in the lower halves of tendoachilles ( Fig. 3 ). Magnetic resonance imaging showed localized homogenous hyper intense signals with fusiform swellings of tendoachilles", "Biopsy of the excised specimen revealed it to be a xanthoma characterized by the accumulation of mononuclear cells with foamy cytoplasm and multinucleated giant cells with high concentration of cholestanol", "short statured", "pain on the left ( non - operated ) tendoachilles disappeared completely although swelling persisted. His walking distance improved. However, had reappearance of the swelling in the reconstructed tendon on the right side, although was not painful", "swellings of both achilles tendons causing signification limitation of walking distance"]}
{"id": "CaseReportBench:train-18", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'A 63-year-old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A-C ) was referred to our hospital due to an abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm ( Fig. 1D ). He had a history of hypertension for 5 years and a smoking habit (10 cigarettes/day). Coronary angiography revealed mild to moderate coronary atherosclerotic lesions ( Fig. 1E and F ). He was initially suspected of having FH based on his physical findings as well as the presence of AAA with a modestly elevated LDL cholesterol level (166 mg/dL). He was born to consanguineous parents (second cousins). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis. Recessive inherited disease was speculated at this point, so we investigated his genetic background using whole-exome sequencing, assuming a recessive form of inheritance. The mean depth was 99.9× per base across the whole exome. The percentage of on-target reads was 84.6%. Also, the coverage rate of target coding lesions (10×) was 99.0%. Bioinformatics analyses and segregation pattern matching followed by exome sequencing were performed for the patient to identify causative variants. The number of aligned variants in the patient that passed the standard quality control was 142,508. Of those, 15,335 were missense, nonsense, splice site, and frameshift variants. After removing “common” variants ( 10 ), 3,042 variants were detected. Subsequently, filtering against the segregation pattern assuming the recessive form of inheritance with the use of an in silico annotation prediction tool (scaled C-score >20) reduced the candidate variants to homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene (c.410G>A or p.Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ). Accordingly, an increased serum level of cholestanol was found (5.2 μg/mL, reference range 1.62-3.08). The patient did not show any neuropathy, although T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging showed periventricular white matter. Other classical phenotypes of CTX, such as juvenile cataract, chronic diarrhea, and intellectual disability, were not found. Endovascular repair (EVAR) was successfully performed for the treatment of his saccular type AAA. Atorvastatin 10 mg was used to reduce his LDL cholesterol, although chenodeoxycholic acid was not used due to the lack of neuropathy.'}", "questions": ["What was observed regarding the patient's Achilles tendon?"], "ground_truth_arguments": ["prominent Achilles tendon thickness"]}
{"id": "CaseReportBench:train-390", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}", "questions": ["What laboratory abnormalities were reported, including lipid profile, inflammatory markers, and cerebrospinal fluid protein levels?", "What findings were observed on Doppler ultrasound of the urinary system (kidney, cyst, bladder)?", "What brain MRI abnormalities characteristic of cerebrotendinous xanthomatosis were identified in this patient (white matter changes, atrophy, T2/FLAIR hyperintensity, dentate nucleus involvement)?", "What changes were described in the six‑year follow‑up cerebellar MR imaging, and what do they suggest about disease progression?", "What imaging abnormalities were found in the lower limbs and ankle, including X‑ray and MRI findings (soft tissue swelling, tendon enlargement, signal characteristics, plantar fat thickening, exudation)?", "What type of genetic alteration in the CYP27A1 gene was reported by targeted sequencing to confirm the diagnosis?"], "ground_truth_arguments": ["There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging ( MRI ) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene ( c.435G > T, c.1263 + 1G > A )", "The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W / FLAIR ( fluid - attenuated inversion recovery ) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei ( DN ) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX", "A 6 - year MR follow - up study revealed that cerebellar hyperintensity in T1 - weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation.", "high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 ( c.435G > T, p. Gly145Gly ) and intron 7 ( c.1263 + 1G > A ) of the CYP27A1 gene.", "X - ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally ( Figure 2E ). Sagittal and axial magnetic resonance imaging ( MRI ) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon ( consisting of low signal intensity on both T1- and T2 - weighted images ), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon", "Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy ( Figure 2 G and H ). ', ' Laboratory examinations ' : ' The laboratory results ( Table 1 ) were as follows : Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high - density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone ( ACTH ) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position ( Figure 2D ). Cerebrospinal fluid protein was mildly elevated : 680.4 mg / L ( normal range : 150 - 400 mg / L ).", "Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene"]}
{"id": "CaseReportBench:train-241", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'A 29-year-old male patient presented with a 6-year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk. He complained of skin tightness around the abdomen while walking. He wandered to and fro between different specialists but without much help. He was diagnosed as Type 1 diabetic 6 years back and was receiving insulin since then. Cutaneous examination revealed large ill-defined hyperpigmented indurated plaques extending symmetrically from mid-truncal area to both thighs characteristically sparing the knees and medial aspect of buttocks. A prominent constriction band was noted around the abdomen. The lesions over thighs were associated with hypertrichosis and were warm to touch. Examination also revealed short stature (145 cm), hypospadias, micropenis, scrotal swelling, and mild hepatomegaly and inguinal lymphadenopathy. Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal. Nails and teeth were normal. Ophthalmologic and auditory examinations were normal. On the basis of cutaneous findings, we kept differential diagnosis of morphea profunda, pseudoscleroderma, POEMS syndrome, Rosai–Dorfman syndrome, pigmented hypertrichotic dermatosis, and scleredema as the possibilities. A deep skin biopsy was done from the indurated plaque on the lateral part of the left thigh and sent for histopathology. Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes. Routine laboratory investigations revealed a fasting blood glucose level of 250 mg/dL and random blood sugar of 338 mg/dL with glycated hemoglobin 10.2%. Thyroid profile, liver function, kidney function, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibody was negative. Ultrasound abdomen revealed mild hepatosplenomegaly and abdominal lymphadenopathy. Color Doppler study of the scrotal region revealed small penis, normal echotexture, no calcific plaques, and small left testis. Chest radiography and nerve conduction studies were normal. Computed tomography (CT) demonstrated marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees. Para-aortic and inguinal lymphadenopathy and mild pericardial effusion were noted. Marked thickening of the scrotum was seen. A diagnosis of “H syndrome” was made. Genetic testing was not possible due to resource constraints.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.'}", "questions": ["What is the patient's recorded height as documented in the physical examination?"], "ground_truth_arguments": ["short stature ( 145 cm"]}
{"id": "CaseReportBench:train-80", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'CASE REPORT': \"A 27-year-old male, presented to our clinic with a history of foreign body sensation in both eyes for the previous 2 years. He had a history of blistering skin lesions on the photo-exposed areas of the body for the past 12 years. At first, blisters started developing over the lower extremities and then gradually involved upper extremities and face. There was also a history of hyper-pigmentation and scarring of the photo-exposed areas of the body. He developed severe pain in the fingers of both hands 1-year prior presentation. He complained of the passage of red colored urine for the past 1 year. There was no history of acute abdominal pain and no family history of the similar phenomenon was found. Striking features on physical examination were a pinched up nose, scarring over the lips, nose, hands, and resorption of distal phalanges of all the fingers in both hands except onycholysis of the smallest digits. Onycholysis was present on all the toes. The remainder of the systemic examination was noncontributory. The patient's uncorrected visual acuity was 20/40 in both eyes. Best corrected visual acuity was 20/20 in both eyes with a correction of –0.5 × 115° in the right eye and –1.25 × 80° in the left eye. Air-puff tonometry measured intraocular pressure of 14 mm-Hg bilaterally. The fundus examination was unremarkable. Slit-lamp examination indicated scleral necrosis in the interpalpebral area of both eyes that was more pronounced temporally compared to nasally. Temporally, it was 4 mm × 3 mm in the left eye and 3 mm × 3 mm in the right eye. Nasally, minimal scleral necrosis was seen with overlying fibrosed conjunctiva in both eyes. Mild conjunctival scarring was present in the temporal necrosed part of the right eye. In the left eye, the temporal necrosed part was devoid of conjunctival tissue, a frill of conjunctival tissue was present at the margin of the necrosed area. Conjunctiva and sclera in the covered area appeared to be normal. Infiltrations were seen in the peripheral cornea of both eyes near the limbus with temporal and nasal involvement. Fluorescein staining indicated normal epithelium. Schirmer's test 1 was 8 mm in the right eye and 10 mm in the left eye. These symptoms were suggestive of porphyria. Laboratory testing based on the definite pattern of accumulation and hyperexcretion of porphyrins and porphyrin precursor is the most effective measure for diagnosis and typing of porphyrias. Exact porphyrin isomer identification requires sophisticated equipment such as high-performance liquid chromatography which is unavailable at our center and in most hospitals in the developing countries. Hematological tests reported hemoglobin, 9.8 g/dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase (423U/l) and mild increase in serum bilirubin (1.8 mg/dL). Ultrasonography of the whole abdomen showed splenomegaly (17 mm). These features are suggestive of hemolytic anemia. The treatment involved complete avoidance of sunlight and use of dark goggles. The patient was prescribed topical cyclosporine 0.5% eye drop 3 times a day and ocular lubricant was prescribed for both eyes. We planned a full-thickness scleral patch graft with amniotic membrane transplant in the necrosed region. The patient was advised to return for periodic follow-up to our cornea clinic.\"}", "questions": ["What measures were recommended to reduce the patient's exposure to light?"], "ground_truth_arguments": ["The treatment involved complete avoidance of sunlight and use of dark goggles ."]}
{"id": "CaseReportBench:train-554", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'2. Case Presentation': 'A 19-year-old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents (cousins). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally. On physical examination, there was diffuse palmoplantar keratoderma ( Figure 1 ). Intraoral examination revealed complete edentulous ridges with normal overlying mucosa. In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X-ray, and skull X-ray were normal. She was subsequently provided with artificial dentures and she was a candidate for mandibular bone graft from her skull and dental implants of lower jaw. Complete blood count and liver function tests were also normal. The patient was informed of the indication, and risks and benefits of fiberoptic nasal intubation under sedation. Preoperatively, after careful intravenous catheter insertion, she was premedicated with intravenous midazolam 1 mg and glycopyrolate 0.2 mg. Topical nasal vasoconstriction was achieved with oxymetazolin nasal drop and xylocaine spray 10% in both nostrils. Nasal oxygenation through the nasopharyngeal airway with 100% oxygen was started 3 minutes before the nasal intubation. The patient received a loading dose of dexmedetomidine (Precedex) 1 µg/kg infused over 10 minutes, followed by maintenance dose of Precedex (0.4 µg/kg/h). Gently, she was intubated by fiberoptic. During the awake nasal intubation, the patient’s SpO 2 remained between 97% and 100%. The heart rate varied from 82 to 96 beat/min. Fentanyl (1.5 µg/kg), propofol (2 mg/kg), and cisatracurium (0.15 mg/kg) were used for induction, and general anesthesia was maintained with Sevoflurane, 50% oxygen and 50% nitro oxide. Vital signs were stable during the surgery. Fentanyl (50 µg) and cisatracurium (2 mg) were repeated every 45 minutes. At the end of the surgery, the patient was extubated when she was fully awake and shifted to post anesthesia care unit (PACU) and had a recovery without any complication. Informed consent was taken from the patient regarding the publication of information in the journal. The patient reviewed the case and gave written permission for the authors to publish the report.', 'Case Presentation': 'We report a 19-year-old girl with palmoplantar hyperkeratosis who presented total loss of her teeth. She was candidate to mandibular bone graft and lower jaw dental implants under general anesthesia.'}", "questions": ["What abnormalities were identified on the panoramic radiograph, specifically regarding the maxillary and mandibular bones and the maxillary sinuses?", "What findings were reported from the physical examination of the chin and from other systemic examinations, routine laboratory tests, chest X‑ray, and skull X‑ray?", "What were the results of the complete blood count and liver function tests?"], "ground_truth_arguments": ["In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X - ray, and skull X - ray were normal", "Complete blood count and liver function tests were also normal"]}
{"id": "CaseReportBench:train-462", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["Describe the respiratory pattern observed in the patient during the clinical evaluation.", "What findings were reported regarding diaphragm mobility from imaging or functional studies?", "Detail the features of the acute respiratory dysfunction at age 45, including gas exchange abnormalities and the underlying cause.", "What explanation was given for the hypercapnia observed in this case?", "Did the respiratory insufficiency recur during hospitalization, and what were the associated observations?", "How did the patient's respiratory function change after receiving immunoglobulin therapy?", "According to the report, how was the respiratory insufficiency attributed to mitochondrial myopathy and which muscle groups were implicated?", "Summarize how the term 'muscular respiratory insufficiency' is used to characterize the patient's condition."], "ground_truth_arguments": ["abnormal respiratory pattern", "Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm", "acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "hypercapnia due to muscular respiratory insufficiency", "The diaphragm was moving normally.", "respiratory insufficiency with hypercapnia recurred", "Under this regimen respiratory function further improved", "hypercapnia due to muscular respiratory insufficiency", "Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra - ocular and the axial muscles but also the shoulder girdle and respiratory muscles.", "muscular respiratory insufficiency"]}
{"id": "CaseReportBench:train-501", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What gastrointestinal symptoms did the patient experience?"], "ground_truth_arguments": ["nausea,"]}
{"id": "CaseReportBench:train-189", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 52-year-old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene. Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme. We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme. After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What is the patient's age, gender, and ethnicity?", "What systemic diagnoses have been recorded for the patient?", "Which antiglaucoma medication is the patient using, and what is its dosing schedule?", "For what clinical purpose was the patient referred to your service?"], "ground_truth_arguments": ["A 52 - year - old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication ( Timolol 2 / day ) was referred to our service to assess the performance of a keratoplasty"]}
{"id": "CaseReportBench:train-467", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': \"The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. The proband (III-1) ( Fig. 1 ) was a 37-year-old man with severe dizziness and double vision. He had first experienced visual and gait disturbances at 10 years of age. The neurological examination performed on admission revealed mild disturbance of cognitive function (Revised Wechsler Adult Intelligence Scale: total IQ=73, performance IQ=58, verbal IQ=91). Neurological disturbances were observed including bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze-evoked nystagmus, and dysarthria. The light reflex was prompt. No disturbances in cranial nerves I, VII, VIII, and XII were detected. Tremor appeared in his neck, but other involuntary movements including palatal myoclonus were not observed. While his upper and lower limbs showed no paralysis, they exhibited severe cerebellar ataxia and hypotonia. No abnormal findings were detected in his deep tendon reflex and sensory system. Ophthalmological examination revealed atrophy of the optic nerve, but there were no pigmentation changes of the retina. Blood and cerebrospinal fluid analyses were normal. Ergometer exercise did not up-regulate his serum lactate and pyruvate. Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1-weighted imaging, and high signal intensities on T2-weighted imaging, suggesting degeneration ( Fig. 2C and D ). The patient was diagnosed as having LHON plus olivocerebellar degeneration. Although the thyrotropin-releasing drug taltirelin did not relieve his symptoms, adenosine triphosphate disodium reduced his dizziness. The patient's mother (II-2) and uncle (II-3) also had optic neuropathy, but other neurological abnormalities such as ataxia and dystonia were not observed. The patient's mother has a history of subarachnoid hemorrhage. MRI of his mother disclosed mild atrophy of the optic nerve ( Fig. 2E ), pons, and cerebellum ( Fig. 2F-H ). No signal changes were observed in the inferior olivary nucleus ( Fig. 2F-H ). We were unable to confirm the detailed clinical information of the proband's grandmother (I-2).\", 'Mutation analyses of mtDNA': \"Blood samples were obtained from the patient and his mother with their informed consent, and the methods used were approved by the institutional review board of Tottori University Hospital. Both mtDNA and genomic DNA were extracted by standard procedures. The polymerase chain reaction (PCR) was carried out using the primers 5'-CCTCCCTACTATGCCTAGAAGGA-3' and 5'-TTTGGGTTGTGGCTCAGTGT-3' for ND4, including 11778G analysis, and 5'-AGTTCAGACCGGAGTAATCCAG-3' and 5'-AGGGTTGTAGTAGCCCGTAG-3' for ND1 . The primer set for ND4 was designed to identify G11778A mutations, which is the main mutation for LHON. The primer set for ND1 was designed to detect not only the T3394C mutation as a minor mutation for LHON but also an A3243G mutation that is frequently detected in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. PCR products that included the previously reported candidate abnormal points were analyzed by capillary electrophoresis using an automated DNA sequencer. The G11778A and T3394C mutations were identified, while the A3243G mutation was not detected. The mutations in the mtDNA were confirmed by performing PCR-restriction fragment length polymorphism (RFLP), in which the PCR products were digested using either HaeIII (for T3394C) or Tsp45I (for G11778A). In order to quantify the heteroplasmic mutation of G117 78A, we prepared vector constructs including 11778G or 11 778A, and semiquantitative analyses of G11778A were performed using a mixture of each with several rate standards (described in Fig. 4 ). Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr-to-His amino acid substitution in ND1. PCR-RFLP data revealed that the T3394C mutation present in both the proband (III-1) and his mother (II-2) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg-to-His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR-RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92% heteroplasmic G11778A mutation, and II-2 had a 70% heteroplasmic G11778A mutation ( Fig. 4C ). Established genetic abnormalities associated with cerebellar ataxia including polyglutamine diseases were not found.\"}", "questions": ["What atrophic changes were described on brain and orbital MRI, including the optic nerve, cerebellum, and brain stem?", "What signal abnormalities on MRI indicated degeneration of the bilateral inferior olivary nuclei?", "What types of mitochondrial DNA alterations were reported for the patient and his mother, and how were they characterized in terms of heteroplasmy?", "What amino‑acid changes are associated with the reported mitochondrial DNA mutations, and which laboratory methods were employed to verify them?", "How did the level of the G11778A mutation differ between the patient and his mother?", "Were any additional common mitochondrial mutations (e.g., A3243G) found in the analysis?", "What were the results of routine blood and cerebrospinal fluid examinations?", "How did serum lactate and pyruvate levels change, if at all, after ergometer exercise?"], "ground_truth_arguments": ["Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus", "Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations.", "Blood and cerebrospinal fluid analyses were normal", "Ergometer exercise did not up - regulate his serum lactate and pyruvate", "Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1 - weighted imaging, and high signal intensities on T2 - weighted imaging, suggesting degeneration ( Fig. 2C and D ).", "The G11778A and T3394C mutations were identified, while the A3243 G mutation was not detected.", "Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr - to - His amino acid substitution in ND1. PCR - RFLP data revealed that the T3394C mutation present in both the proband ( III-1 ) and his mother ( II-2 ) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg - to - His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR - RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92 % heteroplasmic G11778A mutation, and II-2 had a 70 % heteroplasmic G11778A mutation ( Fig. 4C )."]}
{"id": "CaseReportBench:train-504", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What were the findings of the routine hematological and biochemical examinations, including any abnormalities such as anemia?", "What serological investigations were performed and what were their overall results?", "What were the radiographic findings on the chest X‑ray (posterior‑anterior view) and the orthopantomogram?", "What did the neutron activation analysis of the patient’s hair and nail indicate regarding the diagnosis?"], "ground_truth_arguments": ["Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia", "Serological tests like anti - nuclear antibody, anti - cytoplasmic neutrophilic antibody, HIV - I and II, and VDRL were negative", "Chest X - ray posterior - anterior view was within normal limit. Orthopantomonograph ( OPG ) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “ floating in air ” appearance.", "Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis"]}
{"id": "CaseReportBench:train-41", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 38-year-old female presented to the out-patient department with a 6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week. The patient gave no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits. On cutaneous examination, prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin-colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin-colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face. Fundus examination of both eyes showed dark brownish-red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks. 2D-echo and electrocardiogram were investigated to check for cardiac involvement but were normal. A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid-dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material (mucin). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition. Based on the clinical and histopathological findings, a diagnosis of PXE was made. The patient was started on oral and topical sunscreens, advised rigid eye protection to prevent accidental blunt trauma, and regular follow-up.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Describe the chronicity and distribution of the patient's skin changes.", "What visual or neurological complaints has the patient mentioned, and what is their time course?"], "ground_truth_arguments": ["6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week"]}
{"id": "CaseReportBench:train-59", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Description': 'Polyhydramnios in the second and third trimester of pregnancy is defined by (semiquantative) measurements such as a maximum vertical pocket (MVP) >8 cm, or an amniotic fluid index (AFI) >24 cm. Approximately 90% of cases are idiopathic or caused by gestational diabetes (GDM) 1 . However, 10% of cases are associated with fetal structural abnormalities 2 . Most frequent causes are impaired swallowing from any cause (gastrointestinal, facial, musculoskeletal, or brain abnormalities), cardiac failure, hydrops, and renal abnormalities. Metabolic diseases, such as congenital disorders of glycogen storage, are also incidentally reported to present with polyhydramnios in pregnancy 3 . The usual diagnostic work‐up of polyhydramnios is to exclude GDM and maternal infections, and to perform an extensive structural assessment to rule out fetal anomalies. The presence of structural anomalies, involves increased risk of aneuploidy or other chromosomal and syndromic disorders. In isolated polyhydramnios, the risk of perinatal adverse outcome is, however, still increased when compared with uneventful pregnancies 4 . A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios. Aside from a spontaneously closed ventricular septal defect (VSD) in her own infancy, both parents were healthy. A maternal uncle of the mother had died postnatally of an unknown cause. First‐trimester combined test revealed a low risk for trisomies (NT 1.1 mm). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios (uterine size that outpaced gestational age) and premature contractions. She received tocolytics and corticosteroids for fetal lung maturation. Ultrasound showed polyhydramnios (MVP 9.9 cm, AFI 27.5 cm) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles (11 mm). Amniotic fluid drainage (1.8 L) was performed in an attempt to cease the premature contractions. More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna (12 mm) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm (slightly below p3, with head circumference p50, Fig. 1 A). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD. QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 (11q22.1), including exon 1 of the contactine 5 ( CNTN5 ) gene. This variant is not reported as genomic variant in the normal population, neither known to be associated with a genetic disorder or malformation. A relation with the clinical signs appears unlikely. Maternal serum infection testing (TORCHES) was also normal. Two days later (26 + 0), she spontaneously delivered a boy of 835 g (−0.5 SDS), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively. At birth, he was started on CPAP and transported to the neonatal intensive care unit. Physical examination showed a hypotonic infant with a lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus (Fig. 1 B). He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges. The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels. Testes were not palpable in the scrotum. Postnatal cardiac ultrasound confirmed the presence of a small VSD. Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy. A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome. He developed hypotension and was treated with fluid boluses and inotropic support and antibiotics. Despite stabilization of blood pressure and systemic circulation, he developed a progressive lactate acidosis with extremely high plasma lactate: 19.1 mmol/L and high pyruvate: 269 μ mol/L. The L/P (lactate/pyruvate) ratio was 71, which is strongly increased (normal <20). Organic acid analysis in urine showed a strong increase of lactate (56540 μ mol/mmol creatinine) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal. In the absence of secondary causes, these findings are consistent with primary lactic acidosis, caused by a disorder of the pyruvate metabolism or a mitochondrial respiratory chain defect. Due to the severity of the cumulative problems, the neonate died 2 days after birth. Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst (Figure S1C), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst (Figure S1D). DNA analysis of the PDHA1 ‐gene (most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency) showed no pathogenic mutations. Large deletions, point mutations, and small insertions/deletions in mitochondrial DNA (mtDNA) derived from blood were excluded by next‐generation sequencing (NGS) using the Illumina MiSeq platform and a dedicated bioinformatics pipeline (available on request). For whole exome sequencing, exome enrichment was performed by the Agilent SureSelectXT exome enrichment kit version 4, including the UTR regions. Sequencing was performed by an Illumina HiSeq2000 (San Diego, CA) using a 2 × 100 bp paired‐end recipe. Basecalling, and demultiplexing was done using bcl2fastq 1.8.4.,(Illumina, San Diego, CA) reads were aligned onto the human reference genome (hg19) using BWA 0.5.9., duplicates marked using the PICARD software suite 1.77 (GitHub Enterprise, San Francisco, CA), and variants were called using GATK 2.1‐8. Annotations were added using an in‐house build annotation database, according to UCSC RefGene track, dbSNP137, and the dbNSFP (v2.0). Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing: c.292C>T (p.(Arg98*))and c.1303C>T (p.(Arg435*)). Both are nonsense mutations resulting in a premature stop codon at position p.98 and p.435 of the FBXL4 protein, respectively. The location of these mutations on different alleles (compound heterozygosity) was confirmed by testing the parents. Missense and stop mutations in the FBXL4 gene were reported recently to be associated with severe autosomal recessively inherited mitochondrial encephalomyopathy 5, 6, 7, 8 . Our case is the first case demonstrating a premature prenatal onset of symptoms of FBXL4‐ related mitochondrial encephalomyopathy. The polyhydramnios was the primary sign, leading to the detection of brain abnormalities on more detailed fetal ultrasound examination. This early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements. The cases of FBXL4 ‐related encephalopathy reported so far are characterized by increased serum lactate level, psychomotor delay, hypotonia, failure to thrive, swallowing difficulty, and muscle wasting 6 . Onset of symptoms varied from neonatal onset after term birth, to the age of 14 months 5, 6, 8 . Other reported cases were born at term or premature due to medical intervention for intrauterine growth retardation or reduced fetal movements 5, 6 . The FBXL4 gene is situated on nuclear DNA on chromosome 6q16.1. The FBXL4 mitochondrial protein contains an F‐box in its N‐terminal half, followed by 11 leucine‐rich repeats 9, and is expressed in heart, kidney, liver, lung, pancreas, and placenta 10 . Evidence of the pathogenetic effect of FBXL4 mutations was provided by skeletal muscle biopsies and fibroblasts showing defects in mitochondrial respiratory chain enzyme activities, loss of mitochondrial membrane potential, a disturbance of the dynamic mitochondrial network, and mtDNA depletion 5 . The nonsense mutation p.Arg435* in the FBXL4 gene, present in our patient, was earlier reported in homozygous form in a child of consanguineous parents with early onset mitochondrial encephalopathy, severe hypotonia, cardiomyopathy, MRI abnormalities, increased serum lactate, and premature death 5 . The second mutation detected in our patient (p.Arg98* mutation) has not been reported previously. However, like the other mutation reported, this nonsense mutation leads to nonsense‐mediated decay (NMD, RNA degradation) or a truncated protein 5, 6 . As a result, our patient would have been unable to produce a normal FBXL4 gene product. The mother was pregnant again before exome sequencing had started. Within the prenatal timeframe, exome sequencing lead to the diagnosis of the first child, consequently enabling prenatal diagnosis for the second child. Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child. The VSD in our patient is considered to be a separate finding (familial trait), which is not related to the syndrome. Our case demonstrated a prenatal onset of mitochondrial encephalomyopathy presenting with polyhydramnios, causing premature delivery, and cerebellar atrophy. The neonate was hypotonic and in a poor condition with need for mechanical ventilation, inotropic support, and persistent lactate acidosis. Targeted exome sequencing using a mitochondrial gene panel proved its benefit by revealing compound heterozygous mutations in the FBXL4 gene. Prenatal testing was successfully carried out in the current pregnancy. Direct testing for mutations in the FBXL4 gene should be considered in patients with severe encephalomyopathy with high levels of serum lactate.'}", "questions": ["What ventricular septal defect history was reported for the mother and how was it described?", "What cardiac abnormalities were identified prenatally and confirmed postnatally in the fetus, including myocardial appearance and VSD characteristics?", "What signs of circulatory instability, such as blood pressure abnormalities, were observed in the newborn?", "How was the identified VSD interpreted regarding its relationship to the diagnosed mitochondrial encephalopathy?"], "ground_truth_arguments": ["spontaneously closed ventricular septal defect ( VSD ) in her own infancy,", "The myocardium was hypertrophic with a small perimembraneous VSD", "Postnatal cardiac ultrasound confirmed the presence of a small VSD", "hypotension", "The VSD in our patient is considered to be a separate finding ( familial trait )"]}
{"id": "CaseReportBench:train-582", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case presentation': \"An 11-month-old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full-term by Cesarean section and was the second child of the nonconsanguineous parents. The patient's older sibling was phenotypically female, but died in infancy without a clear diagnosis. Although the karyotype was 46, XY, the patient was raised as female gender since she had female external genitalia. In addition, hyponatremia and an elevated adrenocorticotropic hormone (ACTH) level were detected by tests. The blood pressure at clinic was 80/50 mm Hg. Laboratory analysis revealed that the baby had a mildly elevated cholesterol level of 5.72 mmol/L (normal: 2.85–5.70 mmol/L), but a normal triglyceride level. Her plasma sodium level was 131.7 mmol/L (normal: 135–145 mmol/L) with potassium concentration of 6.61 mmol/L (normal: 3.5–5.5 mmol/L). ACTH was >1250 pg/mL (0–46 pg/mL) with a morning cortisol of 1.23 μg/dL (normal: 4–22 μg/dL). Baseline sex hormone tests revealed luteinizing hormone <0.10 U/L, follicle stimulating hormone 1.78 U/L, testosterone 2.50 ng/dL, progesterone 0.44 ng/dL, estradiol 22.99 pg/mL, and dehydroepiandrosterone (DHEA) sulfate <0.1 μg/dL. Adrenal computed tomography (CT) scan revealed enlarged adrenal glands. Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular-like tissues were detected in the bilateral inguinal regions (left: 0.6 × 0.4 cm; right: 0.7 × 0.4 cm) by ultrasonography. Plasma renin activity (PRA) was 0.11 ng/mL per h (normal: 0.93–6.56 ng/mL per h) with a normal aldosterone level of 8.84 ng/dL (normal: 6.5–29.6 ng/dL). Given ambiguous genitalia, karyotype of 46, XY and decreased DHEA and testosterone levels, the diagnosis of 21-hydroxylase deficiency and 11 beta hydroxylase deficiency were excluded. Lacking hypertension and hypopotassemia, the clinical presentation of salt loss and decreased progesterone also did not support the diagnosis of 17OHD. Without an elevated progesterone level, cytochrome PORD was less considered. The differential diagnosis included 3β-HSD deficiency and LCAH. After the informed consent form was signed by the families and approved by the Institutional Review Board of Peking Union Medical College Hospital, further genetic analysis with gene sequencing indicated it is not defective HSD3B2 (related to 3β-HSD deficiency). However, a homozygous variant c.707_708delins CTT (p.Lys236Thrfs∗47) was found on exon 6 of the STAR gene. A truncated disease-causing protein was predicted with MutationTaster software. The variant mutation was found to cause a frameshift at codon 236 with a stop at codon 282. Both parents were found to be heterozygous for the variant (c.707_708delins CTT, p.Lys236Thrfs∗47) at the same locus of the STAR gene without phenotypic consequences. To further evaluate the family pedigree for mutation carriers, the patient's paternal and maternal grandparents also took part in the gene sequencing. The patient's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes (such as mild amenorrhea in women) were recorded, and there were no abnormalities in physical and laboratory examinations. The results of the patient, her parents, and paternal grandfather and maternal grandmother are shown in Fig. 1 . The genogram of LCAH in this family is presented in Fig. 2 . The patient was prescribed hydrocortisone 10 to 12 mg/m 2 and 9α-fludrocortisone 100 μg/d. Gradually, her skin hyperpigmentation and vomiting disappeared, and she had normal growth and development without adrenal crisis attacks. Her hormone and electrolyte levels remained normal, except for a persistently elevated ACTH level throughout 2 years of follow-up. At follow-up for 2 years, the patient is now 104.5 cm tall and weighs 23.3 kg at the age of 4 years old. Her plasma sodium level is 138 mmol/L with a normal potassium concentration of 4.8 mmol/L. Her ACTH level is still elevated (1176 pg/mL). Her baseline sex hormone levels are testosterone <0.1 ng/dL and progesterone <0.08 ng/dL. The level of PRA (1.06 ng/mL per h) is within normal range.\", 'Patient concerns:': 'A case was reported that an 11-month-old Chinese girl who presented with a sex development disorder and hyponatremia. The clinical and genetic tests were carried out to confirm the diagnosis. The genogram of this case was also explored and analyzed. The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular-like tissue in the bilateral inguinal regions were detected with abdominal ultrasound. She was suspected of having LCAH, and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT (p.Lys236Thrfs∗47) on exon 6 of the STAR gene.'}", "questions": ["What were the patient's blood pressure measurements and did they indicate hypertension?"], "ground_truth_arguments": ["Lacking hypertension"]}
{"id": "CaseReportBench:train-351", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': \"A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency.\"}", "questions": ["At what age was the child first admitted to the hospital for respiratory syncytial virus and seizure-like activity?", "How old was the patient when the MRI that revealed limited myelination was performed?", "What was the age of the patient at the time of presentation with seizures and other neurological symptoms?"], "ground_truth_arguments": ["age of 3 months"]}
{"id": "CaseReportBench:train-26", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case report': 'A 2-year-old boy was referred to our hospital due to developmental delay, ichthyosis, asthma, and recurrent pneumonia. His parents were related but there was no history of asthma, and allergic disorders in his family, and close relatives. He had ichthyosis at birth, and mild intermittent asthma, and 2 episodes of pneumonia also were observed in his first year of life. He had no history of seizure. His physical examination revealed spastic diplegia and brisk deep tendon reflexes in lower limbs. He was not able to stand or walk, independently and his speech was limited to 2–3 meaningful words. Acquisition of other developmental skills was mildly delayed with achieving head control and sitting without support at 5 and 12 months, respectively. Extensive hyperkeratosis and scaling of the skin were seen particularly in the dorsum of hands, skin flexures, and lower abdomen ( Fig. 1 ). Funduscopic examination was normal. Electroencephalography, routine laboratory tests, and chromosomal study were also normal. Magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the deep white matter around the trigons of lateral ventricles ( Fig. 2 ). Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging and parakeratosis consistent with ichthyosis. Molecular genetics study utilizing sequencing of the polymerase chain reaction product using the exon-specific primers revealed a c.370-372 (GGA) deletion mutation in the second exon of ALDH3A2 gene in a homozygote state. Therefore, the diagnosis of SLS was confirmed. The patient was treated, symptomatically with inhaled corticosteroid, and bronchodilator, local paraffin applicants, and rehabilitation therapy.'}", "questions": ["At what age did the patient first develop ichthyosis?"], "ground_truth_arguments": ["at birth"]}
{"id": "CaseReportBench:train-400", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': \"A 22-month-old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control. She was born at full term through normal vaginal delivery. She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time. Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement ( Fig. 1 ). Developmental regression was similar to that in GM2 gangliosidosis, such as Tay-Sachs disease and Sandhoff disease. The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A (%) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol/hr/mg (reference range, 620–1,000 nmol/hr/mg) and 74.3% (reference range, 55%–72%), respectively. Based on these findings, the patient was diagnosed with Sandhoff disease. However, the patient did not show cherry red spot on fundoscopy. At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable ( Fig. 2 ). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale (MAS). Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross-motor domain, by 3 months in language and fine motor domain, and by 2 months in personal-social interaction domain in the Denver Developmental Screening Test II. Dietary assessment revealed that the patient irregularly ingested a soft and blended diet of 70–130 kcal, five times a day, and the mean eating duration was approximately 1 hour. She had difficulty in eating and she showed signs of aspiration (e.g., coughing, gagging). Moreover, she had a poor feeding posture with inadequate trunk and head support. Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas. The patient underwent videofluoroscopic swallowing study (VFSS), and was given barium-containing free water, yogurt (thick liquid), and rice porridge (soft). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time (1.3 seconds) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing ( Fig. 3 ). The patient's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight-for-height Z-score (−0.3) was in the 15th–50th percentile of the World Health Organization (WHO) growth standards. Nutritional evaluation showed that the patient needed a regular daily intake of 989 kcal. However, she could only consume 700 kcal/day, which was less than the required caloric intake. The patient was given supplementary balanced nutrition twice a day. The patient received an intensive dysphagia rehabilitation program for 30 minutes a day, five times a week, for 6 weeks, and it comprised both direct and indirect interventions, such as oromotor facilitation, thermo-tactile stimulation, and lip strengthening, and compensatory techniques, such as postural modification and alteration of the feeding utensil to facilitate swallowing. She was given anti-spasticity drugs for managing spasticity and achieving a stable posture during feeding. After the treatment, she was fed in a semi-reclined position, which reduced the signs of aspiration and the amount of food or liquid leakage from the mouth. However, her nutritional status showed no improvement, with her daily calorie intake decreasing to 600 kcal/day after 4 weeks of admission. At 6 weeks postadmission, her total intake further decreased to 392 kcal/day. Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight-for-height Z-score (−1.6) decreased to the 3rd–15th percentile of the WHO growth standards, which was a sharp decrease of one major percentile line in a short period. Gastrostomy was therefore recommended, but her parents refused the procedure. She was then referred to another hospital for treatment of deconditioning due to dehydration, and she received gastrostomy.\"}", "questions": ["What overall pattern was observed in the hexosaminidase assay performed on white blood cells, and how did the results compare to normal reference ranges?", "What did the brain magnetic resonance imaging performed at 15 months reveal about myelination and any abnormal enhancement?", "What types of test materials were used during the videofluoroscopic swallowing study, and what general oral‑phase and pharyngeal‑phase abnormalities were identified?"], "ground_truth_arguments": ["Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement", "The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A ( % ) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol / hr / mg ( reference range, 620–1,000 nmol / hr / mg ) and 74.3 % ( reference range, 55%–72 % ), respectively", "videofluoroscopic swallowing study ( VFSS ), and was given barium - containing free water, yogurt ( thick liquid ), and rice porridge ( soft ). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time ( 1.3 seconds ) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing"]}
{"id": "CaseReportBench:train-472", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}", "questions": ["What were the patient’s vital sign measurements (e.g., oxygen saturation, heart rate, blood pressure) at the time she suddenly developed dyspnea, muscle weakness, and altered consciousness?"], "ground_truth_arguments": ["SPO 2 86 %", "130 bpm", "blood pressure 80/59 mmHg"]}
{"id": "CaseReportBench:train-494", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Patient 2': 'The elder sister of patient 1 was an 84-year-old woman with a stooping posture presenting with tremors since the age of 60. In her 70s she started walking with the aid of a walking stick. At 82 years of age, she was hospitalized for generalized seizures and disturbed consciousness. CT of T10 revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 e). Brain MRI revealed hyperintense lesions around the white matter (Fig. 2 f); elevated serum and CSF lactate levels were also noted at this time. The mitochondrial DNA analysis of the lymphocytes did not indicate MELAS (m.3243A>G) or MERRF (m.8344A>G) mutations. The patient’s condition remained undiagnosed and she died at the age of 84. CK levels in all her four sons were found to be elevated and her third son was diagnosed with epilepsy. She and her fourth son had also been previously diagnosed with Hashimoto thyroiditis (Fig. 1 ). Patient 1 was examined using pathological, biochemical, and genetic analyses. The Institutional Review Board of Kagoshima University approved this study. Patient 1 gave the written and informed consent for her participation in this study.', 'Histochemical and immunohistochemical studies': 'Frozen biopsies of the biceps brachii muscle specimens were obtained from patient 1. The specimens were sliced into 8 μm sections and placed on aminosilane-coated slides. Histochemical and immunohistochemical procedures were performed as previously described.', 'Histological and immunohistochemical characterizations': 'The muscle fibers ranged from 10 to 80 μm in diameter. Sixty-nine of the 609 Gomori trichrome stained muscle fibers (11.3%) were ragged-red fibers (Fig. 3 a). Cytochrome c oxidase (COX) activity was deficient in many of the ragged-blue fibers that were stained with succinate dehydrogenase (SDH) and COX (233 of 881 muscle fibers, 26.4%) (Fig. 3 b, c), and no blood vessels showing strong SDH reactivity were observed. In NADH dehydrogenase-reactive sections, focal decreases and increases in oxidative enzyme activities were observed. Adenosine monophosphate (AMP) deaminase activity was normal. The random checkerboard distribution of the histochemical fiber types was preserved as shown in the ATPase-reactive sections. Acid phosphatase activity was slightly high in some fibers. Muscle fiber glycogen contents appeared normal and the lipid contents were slightly high in some fibers. Electron microscopy showed abnormal proliferation of mitochondria with paracrystalline inclusions (Fig. 4 ). Fig. 3 Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged-red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged-blue fibers with COX deficiency. a−c Bar 100 μm Fig. 4 Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions that are suggestive of mitochondrial myopathy are shown. a bar 1 μm, b bar 500 nm', 'Mitochondrial DNA analysis': 'In case of patient 1, the total DNA was extracted from the peripheral blood leukocytes and the frozen muscle specimens using the DNeasy Blood & Tissue kit (Qiagen). MitoChip v2.0 (The GeneChip ® Human Mitochondrial Resequencing Array 2.0), which provides a standard assay for the complete sequence analysis of human mitochondrial DNA, was obtained from Affymetrix. The patient’s entire mitochondrial DNA was sequenced using MitoChip v2.0 as previously described. Analysis of the microarray data obtained with MitoChip v2.0 was performed using GeneChip Sequence Analysis Software v4.0 (Affymetrix). In order to reveal the mutations that were confirmed by MitoChip v2.0, a 465-base pair PCR product that spanned all of the mutation sites was screened by DNA sequencing. In brief, 50 ng of the patient’s genomic DNA was amplified using the hot-start PCR method and a forward (5′-CACCATTCTCCGTGAAATCA-3′) and reverse primer (5′-AGGCTAAGCGTTTTGAGCTG-3′). Each PCR product was generated under the following conditions: 15 min at 95°C, 42 cycles of amplification (95°C for 30 s, 61°C for 30 s, and 72°C for 1 min), and 30 min at 72°C. Using a presequencing kit (USB, Cleveland, OH, USA), the patient’s PCR products with abnormal elution profiles were purified, and the appropriate PCR products from relatives and control chromosomes were obtained and sequenced by dye-terminator chemistry using an ABI Prism 377 sequencer (Applied Biosystems, Foster City, CA, USA). The resulting sequences were then aligned and any mutations were evaluated using the Sequencher sequence alignment program (Gene Codes, Ann Arbor, MI, USA). The polymorphic and pathogenic natures of the confirmed mutations were checked against two databases: the MITOMAP ( http://www.mitomap.org/ ) and GiiB-JST mtSNP database ( http://mtsnp.tmig.or.jp/mtsnp/index.shtml ). Using MitoChip v2.0, 37 missense variants were detected in the mitochondrial DNA of the peripheral blood lymphocytes. All of these variants show polymorphisms and are listed in the MITOMAP and GiiB-JST mtSNP databases. Two additional missense variants were detected in the mitochondrial DNA of the muscle homogenate; the variants were m.602C>T in the tRNA Phe gene and m.16111C>G in the D-loop. The variant m.16111C>G is listed as a polymorphism, but the variant m.602C>T is not reported in either database. The m.602C>T variant was also confirmed by direct sequencing. The sequence chromatogram showed a heteroplasmic m.602C>T transition in the muscle homogenate mitochondrial tRNA Phe gene (Fig. 5 a). The proportion of mutant mitochondrial DNA in the muscle was 64.7 ± 1.2% (mean ± SD; the operation was performed thrice). Mutant mitochondrial DNA was not detected in the blood lymphocytes when measured using real-time amplification refractory mutation system quantitative PCR analysis (RT-ARMS qPCR), as previously described. Healthy Japanese controls ( n = 100) did not show these mutations in their blood lymphocytes, at least not within the limits of Sanger’s method for DNA sequencing. Fig. 5 a Sequence chromatogram of the mitochondrial DNA region that encompasses the m.602C>T alteration ( asterisk ) that was obtained from the skeletal muscle of patient 1 (reverse complement). b Schematic diagram of the mitochondrial tRNA Phe cloverleaf structure showing previously reported mutations and the m.602C>T alteration in the D-stem. c Comparison of mitochondrial tRNA Phe from different species. Base pairs, including the 602 nucleotides, are shown in boxes', 'Patient 1': 'A 73-year-old woman (Fig. 1, III-8) presenting with abnormal posture and gait disturbance. Since the age of 63, the patient had a slight stooping posture and a pushed-out waist. At 68 years of age, she started using a walking stick because of her unstable gait. She was diagnosed with hypothyroidism by her family physician and administrated with 25 μg/day levothyroxine; however, her symptoms did not improve. At 70 years of age, it gradually became more difficult for her to climb the stairs. At 71 years of age, she was admitted to another hospital. Doctors suspected myopathy because of elevated serum CK levels. She visited our hospital presenting with prominent paraspinal muscle atrophy and mild proximal weakness of limbs. Hypothyroidism-related myopathy was suspected in her, and hence, the levothyroxine dose was increased to 50 μg/day; however, her symptoms did not improve. She had a family history of bent spine, i.e., in her elder sister (patient 2, Fig. 1, III-5), mother (Fig. 1, II-3), and maternal aunt (Fig. 1, II-4). Physical examination on arrival revealed a marked atrophy of the paraspinal muscles and abnormal posture (Fig. 2 a, b). She also presented with right ptosis, dysarthria, bilateral cataracts, and hearing loss. Her eye movements were normal. But there was moderate weakness of the neck flexion and mild weakness of the proximal limb muscles. Tendon reflexes were symmetrical, and Babinski’s sign was absent. She had poor balance with tandem gait without limb ataxia. Sensory systems were intact and Romberg’s sign was negative. She scored poorly on the attention and calculation tests that are a part of the Mini-Mental State Examination (score: 25 points). Fig. 1 Pedigree of the family. The arrow indicates the proband. The affected individuals are represented by the solid black symbols ; open symbols represent healthy individuals. Gray symbols indicate individuals with elevated CK levels Fig. 2 a The full-length figure indicates the posture of patient 1 showing her pushed-out waist. b The dorsal view shows the marked atrophy of the paraspinal muscles in patient 1. CT of T10 of c patient 1 (age 71), e patient 2 (age 82), and g a healthy female (age 74) reveals the profound atrophy of the paraspinal muscles in c patient 1 and e patient 2, but not in g the healthy female. Brain MRI studies revealed several differences between the patients 1 and 2. d Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter Laboratory data were as follows: serum CK level was 290 IU/l (normal range 45–163 IU/l), resting blood and cerebrospinal fluid (CSF) lactate levels were normal, thyroid-stimulating hormone levels were slightly low at 0.47 μIU/ml (normal range 0.5–5.0 μIU/ml). Under the administration of 50 μg/day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U/ml (normal range <0.3 U/ml), antithyroid peroxidase antibody levels were high at 46.5 U/ml (normal range <0.3 U/ml), rheumatoid factor levels were high at 152.3 IU/ml (normal value <15.0 IU/ml), antinuclear antibody levels were mildly elevated (titer of 1:80). Autoimmune analyses, including anti-Jo-1, anti-RNP, anti-SS-A, and anti-SS-B, were negative. The oral glucose tolerance test (75 g) was within normal limits, but Holter monitoring revealed high-frequency premature contractions. Pure-tone audiometry indicated sensorineural and high-frequency hearing loss. Needle electromyographic findings of the biceps brachii and rectus femoris muscles indicated mild myopathic features. Computed tomography (CT) of the thoracic spinal nerve 10 (T10) revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 c). Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery imaging showed moderate cerebellar and temporo-parieto-occipital lobe atrophy (Fig. 2 d). MR spectroscopy revealed the absence of increased lactate peaks. 123I-IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions.', 'Biochemical studies': 'Enzyme activity levels, blue native polyacrylamide gel electrophoresis (BN-PAGE), and other biochemical measurements of the frozen muscle specimens from patient 1 were performed as previously described. All respiratory chain enzyme activities, which are expressed as a percentage of the normal control values relative to the citrate synthase activity, were greater than 20% (Table 1 ). BN-PAGE revealed no abnormalities in either the respiratory chain complexes or their molecular assembly structures. Table 1 Enzymatic activities for mitochondrial respiratory complexes in patient 1 CI activity (CI/CS) CII activity (CII/CS) CIII activity (CIII/CS) CIV activity (CIV/CS) CS activity Patient 1 0.1938 (0.7027) 0.2723 (0.9874) 1.2737 (4.6192) 0.0579 (0.21) 0.2757 Control 0.3194 (1.6183) 0.2751 (1.3444) 1.3132 (6.5512) 0.0826 (0.3840) 0.2151 Patient 1/control ratio 60.7% (43.4%) 98.9% (73.4%) 97.0% (70.5%) 70.1% (54.7%) Enzymatic activities for individual mitochondrial respiratory complexes are given in nmol/min protein, and represent percentage of normal control ( n = 10) mean relative to a reference enzyme of citrate synthase (CS) The activities are relatively low in complex I and complex IV compared with other complexes CI complex I, CII complex II, CIII complex III, CIV complex IV'}", "questions": ["Describe the status of the patient's eye movements.", "What cataract-related findings are reported for the patient?", "What hearing impairments are reported for the patient?", "Summarize the pure‑tone audiometry results for the patient."], "ground_truth_arguments": ["bilateral cataracts, and hearing loss", "eye movements were normal", "Pure - tone audiometry indicated sensorineural and high - frequency hearing loss."]}
{"id": "CaseReportBench:train-85", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What were the patient's blood pressure, heart rate, and oxygen saturation before induction of anesthesia?", "What were the patient's blood pressure, heart rate, oxygen saturation, and body temperature during the operation?"], "ground_truth_arguments": ["blood pressure 115/65 mmHg, heart rate 100 beats / min, oxygen saturation rate 97 %", "blood pressure at 120 - 140/60 - 80 mmHg, heart rate 80 - 100 beats / min, oxygen saturation 100 %, body temperature 37.0 - 37.4 ℃"]}
{"id": "CaseReportBench:train-543", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE PRESENTATION': 'A 20-year-old male presented with a gradually increasing swelling of the left testis for 1 year duration. He was otherwise asymptomatic. He was diagnosed to have CAH at the age of 1 year but had defaulted treatment at the age of 4 years. The patient had a strong reluctance to seek medical care due to his poor socioeconomic status and fear of receiving an unfavourable prognosis. Genital examination revealed a large hard indurated swelling of both epididymes more prominent on the left side. Left testis was ill-defined with an approximate diameter of 3.5 cm. Ultrasonography showed bilateral enlargement of the testes and epididymes (right testis measuring 41 ml in volume (6.6 cm × 3.7 cm × 2.3 cm), left testis measuring 52.1 ml in volume (6.2 cm × 4.5 cm × 3.6 cm)). In addition, there were bilateral grade-II varicocele. Seminal fluid analysis showed azoospermia. A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma (Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent (Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin (Fig. 3 ). Thus, the histopathological analysis was more in favour of TART rather than Leydig cell neoplasm. A course of prednisolone was started and there was good response. In 6 weeks, there was marked reduction in the sizes of testes with minimal induration. He was followed up for 6 months but was eventually lost to follow up.'}", "questions": ["Can you describe the patient's demographic information and summarize the presentation of the testicular swelling, including side, progression, and duration?"], "ground_truth_arguments": ["A 20 - year - old male presented with a gradually increasing swelling of the left testis for 1 year duration"]}
{"id": "CaseReportBench:train-236", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["What was the infant's heart rate on initial examination?", "Describe the infant's eye appearance, oral mucosa, and anterior fontanelle status at presentation.", "What were the preductal and postductal oxygen saturation percentages on arrival?", "What cardiac murmur was auscultated, including its grade and location?", "What findings were reported on the initial electrocardiogram?", "What did the repeat electrocardiogram show after treatment?", "What were the findings of the echocardiogram performed on the infant?"], "ground_truth_arguments": ["bradycardic", "sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle", "His preductal oxygen saturation was 98 % in air and postductal oxygen saturation was 97 % in air", "he had a 2/6 systolic murmur best heard in the pulmonary area", "His ECG showed broad complex bradycardia", "repeat ECG showed regular sinus rhythm", "An echocardiogram was done, and it was normal"]}
{"id": "CaseReportBench:train-389", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE PRESENTATION': 'A 20-year-old male presented with a gradually increasing swelling of the left testis for 1 year duration. He was otherwise asymptomatic. He was diagnosed to have CAH at the age of 1 year but had defaulted treatment at the age of 4 years. The patient had a strong reluctance to seek medical care due to his poor socioeconomic status and fear of receiving an unfavourable prognosis. Genital examination revealed a large hard indurated swelling of both epididymes more prominent on the left side. Left testis was ill-defined with an approximate diameter of 3.5 cm. Ultrasonography showed bilateral enlargement of the testes and epididymes (right testis measuring 41 ml in volume (6.6 cm × 3.7 cm × 2.3 cm), left testis measuring 52.1 ml in volume (6.2 cm × 4.5 cm × 3.6 cm)). In addition, there were bilateral grade-II varicocele. Seminal fluid analysis showed azoospermia. A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma (Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent (Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin (Fig. 3 ). Thus, the histopathological analysis was more in favour of TART rather than Leydig cell neoplasm. A course of prednisolone was started and there was good response. In 6 weeks, there was marked reduction in the sizes of testes with minimal induration. He was followed up for 6 months but was eventually lost to follow up.'}", "questions": ["What abnormalities were reported on scrotal ultrasonography, including testicular size and the presence of varicoceles?", "What did the seminal fluid analysis reveal regarding sperm presence?", "What histopathological features were observed in the right epididymal biopsy, including cellular morphology and stromal characteristics?", "What findings were reported in the testicular tissue regarding seminiferous tubules, germ cell presence, and Leydig cell collections?", "What did the special stain and immunohistochemical studies reveal about the tissue?"], "ground_truth_arguments": ["Ultrasonography showed bilateral enlargement of the testes and epididymes ( right testis measuring 41 ml in volume ( 6.6 cm × 3.7 cm × 2.3 cm ), left testis measuring 52.1 ml in volume ( 6.2 cm × 4.5 cm × 3.6 cm ) ). In addition, there were bilateral grade - II varicocele. Seminal fluid analysis showed azoospermia", "A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma ( Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent ( Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin"]}
{"id": "CaseReportBench:train-95", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case History': 'A 32-year-old, mentally retarded female presented with gait instability and right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints. Patient had undergone surgery for cataracts in both eyes 10 years back. On examination patient was found to have ataxia, soft, non-tender swelling along the posterior aspect of both ankle joints, as well as right malar emminence. A preliminary diagnosis of cerebrotendinous xanthomatosis was made and evaluation was started. Lipid profile revealed total cholesterol of 306 mg/dl (LDL 205 mg/dl, VLDL 46mg/dl, HDL 55 mg/dl) and triglycerides of 526 mg/dl. Rest of the blood chemistry was normal. Radiograph of ankle joints revealed soft tissue swellings along the posterior aspect of both ankle joints and calcaneal bones. MRI of ankle joints revealed fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images consistent with tendinous xanthomatosis. MRI brain revealed hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images. Susceptibility weighted images revealed comma shaped hypointense signal of bilateral dentate nuclei. Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma. Serum cholestanol levels were raised (14 1 micromole/liter). With a combined spectrum of clinical, biochemical and radiological findings, a diagnosis of cerebrotendinous xanthomatosis(CTX) was made.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What were the results of the patient's lipid profile and other blood chemistry tests?", "What abnormalities were identified on the radiograph of the ankle joints?", "What did the MRI of the ankle joints reveal regarding the Achilles tendons?", "What signal abnormalities were observed on brain MRI (T2W, FLAIR, and T1W) in the dentate nuclei, deep cerebellar white matter, and posterior limbs of the internal capsules?", "What findings were seen on susceptibility weighted imaging of the brain?", "What lesion was identified in the subcutaneous tissue of the right malar eminence and what did its FNAC reveal?", "What were the serum cholestanol levels?"], "ground_truth_arguments": ["Lipid profile revealed total cholesterol of 306 mg / dl ( LDL 205 mg / dl, VLDL 46mg / dl, HDL 55 mg / dl ) and triglycerides of 526 mg / dl. Rest of the blood chemistry was normal. Radiograph of ankle joints revealed soft tissue swellings along the posterior aspect of both ankle joints and calcaneal bones. MRI of ankle joints revealed fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images consistent with tendinous xanthomatosis. MRI brain revealed hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images. Susceptibility weighted images revealed comma shaped hypointense signal of bilateral dentate nuclei. Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma. Serum cholestanol levels were raised ( 14 1 micromole / liter )."]}
{"id": "CaseReportBench:train-500", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case presentation': 'We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia. She received critical care symptomatic management including mechanical ventilation. The diagnosis was based on a positive urine test for porphobilinogen and confirmed by the presence of a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). This work has been reported in line with the SCARE criteria . A 24 year-old- single female patient was admitted because of right lower abdominal pain and distension for 2 weeks. The pain was colicky, episodic, with no precipitating factors and only relieved after bowel motion. She had no constitutional symptoms of chronic illness. She was not on any medications and her social history was unremarkable. Her menstrual cycle was regular and she was menstruating one day after admission. Physical examination revealed a thin patient in mild pain distress with normal vital signs. Her abdomen was soft and lax with normal bowel sounds. Routine laboratory tests including CBC and renal and liver function tests were normal. Serum transaminases remained normal during her hospital stay. Aspartate aminotransferase (AST, SGOT) range was 18–33 U/L (normal range: 15–37 U/L). Alanine aminotransferase (ALT, SGPT) range was 25–51 U/L (normal range: 14–63 U/L). On admission, level of serum sodium (Na) was normal: 138 mEq/L (normal range 135–145 mEq/L) and remained normal (range: 135–139 mEq/L) until the 5th postoperative day (see below). Plain abdominal X-ray and abdominal computed tomography (CT) showed a distended cecum located in the pelvis with fecal impaction; the rest of the viscera were unremarkable. These findings were consistent with mobile cecum syndrome. The patient was scheduled for laparoscopy and possible laparotomy. The only abnormality during laparoscopy was that the cecum and ascending colon were not attached to posterior abdominal wall. The procedure was converted to laparotomy. Right hemi-colectomy was performed. She was kept on epidural analgesia, intravenous (IV) fluids and nil by mouth for four days and had a smooth post-operative course. After surgery, she received intravenous (IV) 5% dextrose/0.9% NaC) three liters/day (her weight was 48 kg). In addition, her pain was controlled by epidural analgesia of lidocaine and fentanyl. The histology revealed normal colon. On the 5th postoperative day, oral intake was resumed and epidural analgesia was discontinued. Eight hours later, she had a sudden deterioration of consciousness level and became unresponsive with a Glasgow Coma Scale of 7/15. Her pupils were dilated and had a sluggish reaction to light. The patient was immediately intubated, mechanically ventilated, resuscitated, and admitted to the intensive care unit (ICU). Blood work up revealed severe hyponatremia; serum Na: 107 mEq/l with normal renal and liver function tests. Our differential diagnoses for the severe hyponatremia included drug intoxicity, encephalitis, and salt losing nephropathy. Consultations to neurology and psychiatry were made and they advised brain CT scan and magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. These tests and septic work-up were normal. She was extubated two days later. At this stage, she started to complain of acute abdominal pain and developed altered mental status, personality changes, visual and auditory hallucinations with euphoric and aggression episodes despite correction of serum Na. The presence of abdominal pain, neurological and psychiatric symptoms and unexplained severe hyponatremia raised the suspicion of AIP. The diagnosis of AIP was based on the presence of high PBG in the urine (test was done at another center). At no time, her urine was dark. In retrospect, the family history showed that two of her cousins (from mother side) had AIP. The patient condition improved markedly after proper pain control and high carbohydrate intake. We referred her to a higher center where she was found to have a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). There, she received premenstrual regime of IV hematin (heme arginate) 4 mg/Kg body weight/day for three days. She had four recurrent milder attacks in the form of abdominal and back pain and confusion and was treated with similar regime of hematin. Thereafter, she was kept on once monthly prophylactic IV hematin 4 mg/Kg body weight/day for three days. Now, one and a half years after discharge from our service, she is doing fine and on no hematin treatment.'}", "questions": ["What neuro‑visceral and psychiatric manifestations did the patient exhibit during the acute porphyria attack?", "Describe the sudden deterioration in consciousness observed during the acute attack, including any changes in level of alertness and pupil response.", "Which brain imaging studies (CT, MRI) and cerebrospinal fluid analyses were performed, and what were the findings of these tests and the septic work‑up?", "What types of neuropsychiatric manifestations, such as changes in mental status, personality, or hallucinations, were noted during the episode?", "Did the patient experience any recurrent milder attacks after the initial event, and what general categories of symptoms were associated with those attacks?"], "ground_truth_arguments": ["neuro - visceral and psychiatric manifestations", "sudden deterioration of consciousness level and became unresponsive with a Glasgow Coma Scale of 7/15. Her pupils were dilated and had a sluggish reaction to light", "brain CT scan and magnetic resonance imaging ( MRI ), and cerebrospinal fluid analysis. These tests and septic work - up were normal", "developed altered mental status, personality changes, visual and auditory hallucinations with euphoric and aggression episodes", "neurological and psychiatric symptoms", "four recurrent milder attacks in the form of abdominal and back pain and confusion"]}
{"id": "CaseReportBench:train-289", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}", "questions": ["Were any abnormalities noted in the white blood cell count or differential on laboratory testing?", "What was the patient's recorded body temperature, and was it considered elevated?"], "ground_truth_arguments": ["Increased leukocyte count, neutrophil ratio", "T ≤ 38.2 ° C )"]}
{"id": "CaseReportBench:train-261", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["What were the infant's initial respiratory rate and the preductal and postductal oxygen saturation percentages while breathing room air?"], "ground_truth_arguments": ["His respiratory rate was 50 breaths/ min and was saturating at 99 % in air. His preductal oxygen saturation was 98 % in air and postductal oxygen saturation was 97 % in air"]}
{"id": "CaseReportBench:train-571", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to house soiling and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. The environment consisted of two young adult humans with no children. They lived in a flat of 85 m 2, with two terraces of 5 m 2 each. There were three separated litter boxes at home, all of which were non-covered with low sides. The owners had used clumping, non-clumping, silica-based and soil-based litter during the months between the adoption (when the cat was 4 months old) and the first visit. One of the latrines always had clumping substrate. There were three food and three water troughs, all of them far from the latrines. The impression of the owners was that the cat eliminated where it was at any given moment. It eliminated many more times in front of the owner (90%) than when it was alone (10%). The cat never tried to cover its faeces or urine after depositions. Occasionally, the owners punished the cat verbally and physically, but only when it eliminated in front of them. The substrates used by the cat were ceramic tiles, the sofa and beds. It always adopted an emptying-body posture. Spots were always located on horizontal surfaces. The owners used bleach-based products in order to clean the spots, and just water in the case of the sofa and beds. Regarding the play-related problem, the owners said that the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘tried to bite, catch and scratch the air’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat’s behavioural history was unremarkable. The differential diagnoses of the house-soiling problem included problems with the litter trays, including insufficient number, incorrect type, competition with other cats for the latrines, incorrect location, acquired aversion, or inappropriate substrate; a preference for another location or substrate; a problem with preference acquisition (ie, because of a cognitive impairment, or a sensory impairment or an unavailability of appropriate latrines or substrate during the first few weeks of life); and marking behaviours. Finally, a medical illness can contribute to all of these problems or to be the main cause. 1, 2 We could rule out most of these problems after interviewing the owners. Firstly, it was unlikely that there was a problem with the litter tray because the number, type and location were correct. The locations were correct because the animal eliminated near the litter tray if it was there. Many different substrates had been used. Secondly, it was not a problem of preference because the cat eliminated in different locations and surfaces. The age of the animal, the distribution of the spots and the body posture during elimination ruled out marking behaviours. Alterations in play behaviours described by the owners could have been due to a cognitive impairment, and/or a sensory impairment (ie, blindness). Play behaviours depend on learning capability and sensory systems. 3 Additionally, an enriched environment is necessary to learn and display play behaviours in a proper manner. 4 In that case, the social and instrumental environment was good. Regarding elimination, a problem of substrate preferences acquisition was diagnosed. A cognitive impairment, a medical condition or both could have been the cause of the problem during the elimination habits acquisition. Moreover, cognitive impairment and some medical conditions also could explain the play-related behavioural problems. During the consultation, the physical examination was unremarkable; however, the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. A complete ophthalmological examination was performed by the ophthalmological service in order to rule out ocular diseases. No ophthalmological abnormalities were detected. Additionally, based on the behaviours at home described by the owners (the inability to find some toys, and the behaviour of ‘scratching and biting the air’), some degree of visual impairment was suspected but not confirmed with the neurological examination. The cat did not crash with objects either at home or at the consultation room. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits. The feline immunodeficiency virus/feline leukaemia virus test was negative. A thorax radiograph, abdominal ultrasound, brain magnetic resonance imaging (MRI; 0.2 T) and cerebrospinal fluid analysis showed no abnormalities. Although some small lesions could be missed with low-field MRI, we had to assume the absence of lesions obtained in the work-up. Thus, a degenerative condition such as a lysosomal storage disease, organic aciduria or mitochondrial encephalopathy was suspected. Samples of blood and urine were sent to the University of Pennsylvania School of Veterinary Medicine for metabolic screen tests. Amino acids, organic acids, carbohydrates, nitroprusside, ketone and mucopolysaccharide concentrations were analysed, as was α-mannosidase, β-mannosidase, fucosidase and hexosaminidase A and B activity. All of these were within normal limits. No treatment was prescribed for the neurological problem. The owners were given advice on correcting the soiling problem in the house using reward-based training with a clicker. During the first week, the clicker was conditioned by a food reward, and the entire floor was covered with newspaper. Each time that the cat eliminated, it was rewarded with a clicker and food. Newspaper was removed progressively. Three months later, the cat used a small newspaper-covered area to eliminate. This partial improvement suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability. After 3 months, the cat was referred to the neurology service again, in status epilepticus. Neurological findings, after the postictal phase, included a lack of bilateral menace response and cerebellar ataxic gait. A bilateral carpal valgus that had already been found in the first visit and a visible suture line in the posterior capsule of both crystalline lenses were also detected. The owners reported progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status (probably seizure activity). A symptomatic treatment with diazepam (1 mg/kg intrarectally only if seizures) and phenobarbital (2 mg/kg PO q24h) was started, with a very poor response. After 15 days of treatment, levetiracetam was added (10 mg/kg PO q8h) owing to an increase in seizure activity, with an initially good response. However, seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting <2 mins. After 2 years of treatment and a progressive worsening, the cat was euthanased. A complete necropsy was immediately performed. No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS. In order to rule out prion aetiology, a PrPsc inmunohistochemistry assay was performed, and the results were negative. Thus, congenital spongiform polioencephalomyelopathy (CSP) was diagnosed postmortem. Spongy vacuolation seen by light microscopy in the neural tissue is defined as spongy degeneration, and may take the form of vacuoles within processes of the neuropil, vesiculation of myelin sheaths, or swelling of astrocyte or oligodendrocyte cytoplasm. 5 A congenital problem, retrovirus infection and prion disease have been suggested as possible aetiologies. 6 – 10 Congenital spongiform degeneration of the grey matter has been previously described in a few cases of cats; 6 – 8 however, the cause remains still unknown. Common clinical signs include gait alteration, seizures, blindness, bilateral cataracts, behavioural changes and cranial nerve alterations. These signs appear during very early stages of development (just after birth), with a progressive fatal outcome in a few days or months. Behavioural signs are poorly described in animal science literature. 6 – 8 Although the degeneration usually affects diffusely all the grey matter, the behavioural alterations and the evolution of the clinical signs depend on the affected area of the brain in each case. Nevertheless, the clinical signs do not always correlate with the degree of the histological lesions. A spongy degenerative problem of grey matter has also been described in humans, and occurs in isolated cases and in sibs. 11 – 13 In all of human cases reported, the problem appears early in infancy and the outcome is always fatal. All the affected children show learning disabilities (ie, retarded speech development) during the early periods of infancy. Additionally, they rapidly develop neurological signs, especially seizures. The clinical findings and neuropathological changes are very similar in humans and the present case. There are no studies regarding degeneration of grey matter and its effect on learning ability in animals. However, other neurodegenerative problems (ie, lysosomal storage diseases) and problems that lead to structural abnormalities of the forebrain (ie, hydrocephaly) may be correlated with learning disabilities in animals and humans. 14 – 17 The acquisition of the elimination habits occurs during the first weeks of a kitten’s life. Most kittens naturally seek out sand-like materials for elimination purposes. However, the preference for a substrate needs to be learnt during those first weeks of age. Learning disabilities and/or sensory impairments could modify the acquisition of these habits.'}", "questions": ["What were the findings of the complete ophthalmological examination performed to rule out ocular disease?", "What home behaviors prompted owners to suspect visual impairment, and was this impairment confirmed on clinical examination?", "Did the examinations reveal any ocular structural abnormalities, and if so, what were they?"], "ground_truth_arguments": ["No ophthalmological abnormalities were detected", "based on the behaviours at home described by the owners ( the inability to find some toys, and the behaviour of ‘ scratching and biting the air ’ ), some degree of visual impairment was suspected but not confirmed", "visible suture line in the posterior capsule of both crystalline lenses were also detected"]}
{"id": "CaseReportBench:train-210", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case Report': 'At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine. She was born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively. As a 3-week-old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed. At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day. Physical examination revealed multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back. The spleen was of normal size and physical and intellectual development was normal. Again, moderate hemolytic anemia was also found (red blood cells: 3.68 × 10 6, hemoglobin: 10.6 g/dl, hematocrit: 33.0%, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G/DL, platelets 124 × 10 3 ml, white blood cells: 3.6 × 10 3, reticulocytes: 58 (5-15)), but did not require a blood transfusion. Further laboratory investigations were as follows: urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal. Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable. Now, aged 14 years, the severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands. Using all available measures to protect herself from the sun (hat, eyeglasses, cosmetic camouflage, and long sleeves) has not succeeded in protecting her from the mutilating effects of sun. This has caused scarring of her skin at sun-exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp. In addition, she has restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust. Moderate hypertrichosis on the back of the neck was also noted and her teeth have progressively stained brownish-red. The results of the biochemical investigations are summarized in Table 1 . Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High-pressure liquid chromatography of the urine demonstrated 85% of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617. These results confirmed a diagnosis of CEP. Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T>C (p.Cys73Arg) in exon 4 and c.683c>T (p.Thr228Met) in exon 10. These missense mutations have previously been described, where the patient had a moderate to severe phenotype.'}", "questions": ["Summarize the pregnancy and delivery, noting whether the birth was at term and if any complications occurred, and give an approximate description of the newborn's size (weight and length)."], "ground_truth_arguments": ["born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively"]}
{"id": "CaseReportBench:train-103", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE REPORT': 'A 12‐year‐old girl, born from consanguineous marriage, was presented with a five‐year progressing bilateral, symmetrical, hyperpigmented, and thickened patches with hypertrichosis. These lesions were present not only in the inner thighs but also in pubic and lumbar regions. On examination, she has gluteal lipodystrophy, swelling with hyperpigmentation of labia majora as well as finger and toe flexion contracture (camptodactyly and hallux valgus), and deformation of teeth (Figure 1 ). Erythematous, annular, and figurate lesions slightly keratotic without atrophy were present in cheeks and nose (Figure 2 ). Dermoscopy revealed multiple telangiectasias drawing a reticulated network (Figure 3 ). A four‐mm punch biopsy showed perifollicular focal para‐keratotic hyperkeratosis of the epidermis. The dermis was slightly edematous and contain ectatic capillaries. There was a lymphocytic and histiocytic infiltrate (Figure 4 ). IHC was positive for CD68 (Figure 5 ). The diagnoses of a mycological cause, porokeratosis of Mibelli, and sub‐acute lupus erythematous were excluded. She has also been explored for hearing loss in the early childhood with hearing aids. Ophthalmological examination showed chorioretinal atrophy. Biological data showed low hemoglobin (9.5 g/dL) and high erythrocyte sedimentation rate (75 mm/h). The rest of laboratory tests including thyroid function tests, lipid profile, liver function tests, renal function tests, and antinuclear antibodies profile were all normal. Echocardiography and electrocardiogram were normal. Abdominal ultrasound found small uterus and ovaries with thickened skin and subcutis of vulva. Genetic analysis revealed homozygous missense mutation c.1088G>A; p.Arg363GIn in exon 6 in linkage disequilibrium with the same non‐pathogenic variant at intron 2 c.300+3A>G. H Syndrome was diagnosed based on histological, immunohistochemical (IHC) examination and molecular analysis. The unusual feature of this case of H Syndrome was the presence of erythematous annular and figurate lesions that were slightly keratotic in cheeks and nose, thus representing a new clinical feature of H Syndrome.'}", "questions": ["Were any pigmentary abnormalities observed on the patient's external genitalia?"], "ground_truth_arguments": ["hyperpigmentation of labia majora"]}
{"id": "CaseReportBench:train-540", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}", "questions": ["Describe any seizure events the patient experienced before hospital admission, including where and how they occurred.", "What neurological status did the patient attain immediately after the short intravenous anesthesia, and how did her neurological and psychological symptoms evolve in the post‑intervention period?", "Detail the seizures that developed during hospitalization, specifying their type, associated agitation, and progression to epileptic status.", "What level of psychomotor agitation was observed in the patient after the epileptic status resolved?", "Summarize the neuroimaging findings reported, describing any notable abnormalities on CT and MRI."], "ground_truth_arguments": ["seizure attack at home", "reached full orientation and cooperativeness within few minutes. The post - intervention period remained uneventful and the neurological and psychological symptoms returned to the pre - exacerbation status", "patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status", "state of high psychomotor agitation after the epileptic status", "The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico - subcortical distribution, parieto occipital and frontal,"]}
{"id": "CaseReportBench:train-297", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'CASE REPORT': \"A two-month-old female infant was transferred to Seoul National University Children's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg (<3rd percentile). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion. The initial laboratory findings after birth showed the following increased values on the liver function test: aspartate aminotransferase (AST), 176 U/L; alanine aminotransferase (ALT), 106 U/L; total bilirubin, 1.76 mg/dL; and direct bilirubin, 1.2 mg/dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non-diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract. The patient was fed with preterm formula milk without feeding intolerance. No definitive sepsis event occurred during her hospitalization. When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg/dL and a direct bilirubin level of 9.61 mg/dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum-ascites-albumin gradient level was elevated, and portal hypertension was suspected. By the age of 70 days, the infant was transferred to our hospital for further evaluation of persistent ascites suggesting portal hypertension and hyperbilirubinemia. On the day of admission to our unit, the infant's height was 42 cm (<3rd percentile), her weight was 2.9 kg (<3rd percentile), and her head circumference was 33.5 cm (<3rd percentile). A physical examination indicated whole-body jaundice, a markedly distended abdomen with ascites and an umbilical hernia. The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g/dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg/dL, a direct bilirubin level of 6.4 mg/dL, an AST level of 225 U/L and an ALT level of 114 U/L. The albumin level was 2.4 g/dL, and the ammonia level was increased to 149 µg/dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng/mL (normal values are 14.0-647.2 ng/mL), and the transferrin saturation was 97.2%. The serum alpha-fetoprotein level was in the high normal range (19,737.27 ng/mL; normal values are 40-19,953 ng/mL). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging (MRI) verified a diffuse heterogeneous low signal intensity in the liver on T2-weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra-hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non-diagnostic findings. The infant received supportive medical treatment, including fat-soluble vitamins, ursodeoxycholic acid, fresh frozen plasma, lactulose, diuretics, and sodium benzoate. Her general condition and coagulopathy were aggravated, and her vital signs were unstable. She was transferred to the intensive care unit on day 18 of hospitalization for further management. Her mother began the donor evaluation process. Active gastrointestinal bleeding was observed on day 21 of the infant's hospitalization, and an emergency living donor liver transplantation was performed. The infant was 3 months old, and her weight was 3 kg on the day of transplantation. The graft was tailored by reducing its left lateral section. The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining. The infant fully recovered from hepatic failure after liver transplantation. The infant was discharged one month after the operation. She exhibited normal renal function after transplantation. She received medical treatment for hyperkalemia, which occurred after the administration of tacrolimus. Following her discharge, the patient's neurological development was delayed, and she entered rehabilitation with outpatient clinic follow-up in the hospital's neurology department. Assessments by brain MRI and chromosomal study produced normal findings.\"}", "questions": ["What was the gestational age at birth and the mode of delivery?", "What was the infant's birth weight and how did it rank percentile-wise?", "What were the Apgar scores at 1 minute and at 5 minutes?", "Why was the infant admitted to the neonatal intensive care unit immediately after birth?", "What metabolic abnormality was observed shortly after birth and what treatment was administered?", "What did antenatal sonography show regarding fetal hydrops and hepatomegaly?"], "ground_truth_arguments": ["born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg ( < 3rd percentile ). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly."]}
{"id": "CaseReportBench:train-480", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case report': \"A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency.\"}", "questions": ["What was the gestational age at delivery and were any complications reported during the pregnancy or birth?", "Did the case report describe any abnormal fetal movements observed in utero?", "What clinical signs or symptoms were noted for the newborn during the first week of life, specifically regarding muscle tone, irritability, and feeding method or success?"], "ground_truth_arguments": ["born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate"]}
{"id": "CaseReportBench:train-595", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Cases': 'The older patient was 20 years old. She was a product of a full-term spontaneous vaginal delivery at home. She was found to have severe virilized external genitalia: a phallic-like structure with hypospadias and incompletely fused labioscrotal folds. She was raised and named as a boy and no medical advice was sought at that time. Her parents reported that she had behaved as a female since early childhood. She was interested in playing with girls and in girl’s games, although she studied at male schools. She spent most of her time with her girlfriends and felt most comfortable when she dressed as a female. She was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation. Physical examination showed a short male-looking adolescent with acne and Tanner stage IV breast development. Her height was 133 centimeters. Her blood pressure was 140/88. Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An adrenocorticotropic hormone (ACTH) stimulation test showed a baseline cortisol (F) level of 28 nmol/L, ACTH of 201 ng/mL (normal, 0–46), 11-deoxycorticosterone (11-DOC) of 20 nmol/L (normal, 0.49–3.3), 17-hydroxyprogesterone (17-OHP) of 17 nmol/L and testosterone (T) of 7 nmol/L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol/L, the 11-DOC level was 141 nmol/L (normal, 2.2–6.8) and the 17-OHP level was 22 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X-ray. Examination under anaesthesia combined with cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus. Based on her biochemical and radiological evaluation, she was diagnosed as having 11-hydroxylase deficiency and was started on hydrocortisone 10 mg twice a day. She was evaluated by the pediatric psychiatrist who clearly confirmed her female gender identity and her strong wish to be converted to a female. Feminizing genitoplasty (clitoral reccesion) was performed at the age of 16 years and she was given a female name. She admitted her strong desire to get married and to be a mother. The younger patient was 16 years old. He was born at home and raised and named as a boy based on the appearance of the external genitalia. His parents reported that he behaved as a male and was proud of that. He was interested in playing with boys and in boy’s sports. He was dressed as a boy and had a short haircut. He was referred to our clinic at the age of 13 years. Physical examination showed a short stature, a masculine appearance, acne and Tanner stage IV pubic hair and stage II breast development. His height was in the fifth centile. His blood pressure was 130/80 mm Hg. Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol/L, an ACTH of 231 ng/mL, 11-DOC of 40 nmol/L, 17-OHP of 18 nmol/L and a T level of 7 nmol/L. Sixty minutes after ACTH stimulation, the F level was 45 nmol/L, 11-DOC was 114 nmol/L and 17-OHP was 20 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years. He was diagnosed as having 11-hydroxylase deficiency and started on hydrocortisone 10 mg twice a day. His final height was 139 centimeters. He was interviewed by the pediatric psychiatrist who clearly confirmed his male gender identity and his strong wish to continue to be raised as a boy. We had several separate meetings with him and his parents and informed them that he would be an infertile man if he decided to continue to be raised as a man and there was a possibility that he would be a fertile women if he converted to his genetic sex. The patient, however, refused to change to his female genetic sex and admitted his strong wish to be a man forever. After more that one year of counseling and intensive psychiatric interview, he and his parents decided on a hysterectomy “to avoid menarche which might affect him psychologically” as his mother said. Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed. Both patients were satisfied by the way they were managed and raised and there were no postoperative psychological complications.'}", "questions": ["What type of metabolic disorder was each patient diagnosed with?"], "ground_truth_arguments": ["she was diagnosed as having 11 - hydroxylase deficiency", "He was diagnosed as having 11 - hydroxylase deficiency"]}
{"id": "CaseReportBench:train-438", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE REPORT': 'Patient 1 (UPN 1) is a male who was diagnosed with WAS at the age of 5 months. He presented with incidentally detected thrombocytopenia (23,000/µL) with skin eczema and severe, recurrent otitis media and diarrhea on admission. The second male patient (UPN 2) presented with neonatal thrombocytopenia at birth and received intermittent intravenous immunoglobulin (IVIG). Thereafter he experienced skin eczema and recurrent infections such as cellulitis and pneumonia, until he visited our hospital at 3 months old. Flow cytometric analysis of peripheral blood mononuclear cells (PBMC) for these 2 patients revealed a defect in WASP, leading to the diagnosis of WAS. Subsequently, the nonsense mutations, Arg211stop and Arg13stop, were confirmed by genomic analysis ( 17 ). Before transplantation, these patients were treated with monthly infusions of IVIG as well as supportive treatment but there was no clinical improvement. CBSCT was performed in a laminar air flow room with conventional supportive therapy. The pre-transplantation conditioning regimen for the 2 patients was 1 mg/kg of busulfan intravenously every 6 hr on days -9 through -6. This was followed by 50 mg/kg of intravenous cyclophosphamide on days -5 through -3 and 30 mg/kg of intravenous antithymocyte globulin (ATG) on days -3 through -1. Prophylaxis for acute graft versus host disease (GVHD) included continuous infusion of cyclosporine A beginning on day -1, targeting whole blood levels to be 200 to 400 ng/mL, and 1 mg/kg/dose of methylprednisone every 12 hr on days 5 through 19, and then a taper. The degree of human leukocyte antigen (HLA) match confirmed by high resolution DNA typing between the infused CB and the patients was 4/6 for UPN 1 and 5/6 for UPN 2. Infused cell doses of TNC and CD34+ cells for UPN1 and UPN2 were 6.24×10 7 /kg and 5.08×10 7 /kg for TNC, respectively, and 1.33×10 5 /kg and 4.8×10 5 /kg for CD34+ cells, respectively. T-, NK-, and B-cell enumeration and quantitative immunoglobulin studies (for immunoglobulin G, A, M, D, and E) were performed. Cytofluorographic analyses of lymphocyte subpopulations were performed with murine monoclonal antibodies conjugated to either fluorescein (FITC) or phycoerythrin (PE) and then analyzed by flow cytometry (FACScan; Becton Dickinson, San Jose, CA, U.S.A.). Heparinized venous blood samples from patients and family members were fractionated on a Ficoll-Hypaque gradient to isolate PBMCs. For mutational analysis, genomic DNA was extracted from the peripheral lymphocytes, and 12 WASP gene exons were amplified by polymerase chain reaction (PCR) followed by direct sequencing according to the protocol of Sasahara et al. ( 18 ). Hematopoietic reconstitution following CBSCT was uneventful, with an absolute neutrophil count (ANC) of more than 500/µL on days 31 and 13 and a platelet count of more than 20,000/µL on days 58 and 50, for UPN 1 and UPN 2, respectively. Molecular chimerism studies using the VNTR method showed a complete donor cell type for these patients (data not shown). Acute GVHD did not occur, even after the infusion of HLA 1 or 2 antigen mismatched CB. UPN 1 experienced 1 episode of sepsis with B. cepacia during the pre-engraftment period without any complications. UPN 2 experienced fever and respiratory distress with hypoxemia due to pulmonary edema as well as skin rashes on the trunk in the pre-engraftment period (from days 8 to days 10), which mimics engraftment syndrome. He recovered with oxygen supply via endotracheal tube and fluid restriction as well as methylprednisone therapy. Both patients were clinically well without eczematous skin and recurrent infections at 60 months (UPN 1) and 55 months (UPN 2) post CBSCT. Clinical data regarding CBSCT are shown in Table 1 . The elevated total eosinophil counts and serum IgE levels have been normalized since 7 months post-transplantation in both children ( Table 2 ). Other immunologic parameters including IgG, IgA, IgM, IgD and lymphocyte subsets are summarized at Table 2 . To determine whether the genotype was corrected by CBSCT, we analyzed the WASP gene sequence before and after CBSCT in UPN 1. UPN 1 had a single base substitution (C665T) in exon 7 that results in an amino acid change in codon 211 (Arg211stop) before CBSCT. Following CBSCT, UPN1 had a normal sequence at the mutation site in exon 7 of the WASP gene ( Fig. 1 ).'}", "questions": ["What age was patient 1 first reported to have clinical signs or a diagnosis of the disease?", "According to the case description, at what age did patient 2 first present to the reporting hospital with clinical signs of the disease?"], "ground_truth_arguments": ["5 months", "3 months old ."]}
{"id": "CaseReportBench:train-471", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': \"We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).\", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}", "questions": ["What eye‑related manifestations of the disease are described for the patient?"], "ground_truth_arguments": ["angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment"]}
{"id": "CaseReportBench:train-90", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE REPORT': 'A 37-year-old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous (IV) drug abuser that required a permanent indwelling venous catheter for his repeated attacks; so, he had a port since 9 months ago and received pethidine via that port during the attacks. On admission, a chest computed tomography revealed multiple cavities in both lungs. A large mobile veg on anterior leaflet of tricuspid valve commissure (TVC) with severe TR was also demonstrated in his transthoracic echocardiography. After starting antibiotic therapy and removing the port, the patient underwent TV replacement. In the day of surgery, prior to induction, all standard monitorings were applied; radial artery line and subclavian central venous (CV) line was also indwelled after induction. Premedication was consisted of incremental doses of fentanyl and midazolam. We used propofol and atracurium for induction. Maintenance of anesthesia was done by propofol, atracurium, midazolam and fentanyl. Following sternotomy and heparinization, cardiopulmonary bypass (CPB) was initiated. The patient cooled to 32–34°C. Myocardial protection was provided by hypothermic antegrade blood cardioplegic. The TV was replaced. After 70 min of CPB, separation from CPB was achieved, and heparin was reversed by protamine. Rewarming and weaning from CPB was uneventful. Four units of packed cell were given during CPB; Hct was maintained about 30%. Postoperatively, in Intensive Care Unit (ICU), the patient was extubated in 6 h. We started parenteral carbohydrate as dextrose 50% to prevent AIP attack, and the patient was encouraged to become per oral (PO) as soon as possible. Finally, he was discharged from ICU on day 2 after surgery. AB therapy was continued for several weeks. By providing adequate IV crystalloid fluids, we had prevented any dehydration. The patient was cautiously observed for any symptoms of AIP attack. Throughout his stay in ICU, he had no symptoms such as abdominal pain, dark urine, and neurologic deficit.'}", "questions": ["What demographic information is provided about the patient?", "Which symptoms did the patient present with upon admission?", "What chronic condition is mentioned in the patient's history, and when was it initially diagnosed?", "Is there a history of intravenous drug use, and are any long-term venous catheters referenced?"], "ground_truth_arguments": ["A 37 - year - old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous ( IV ) drug abuser that required a permanent indwelling venous catheter for his repeated attacks"]}
{"id": "CaseReportBench:train-330", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case 2': 'An 18-year-old girl was admitted to our hospital following development of generalized tonic-clonic seizure in November 2016. Ten days ago, she was diagnosed with ileus because of abdominal pain as well as constipation in her local hospital. However, the symptoms were not relieved and a series of tests including abdominal X-ray, CT scan, and ultrasound were normal. Her brain MRI was performed in her local hospital indicating PRES (Fig. 3 ). MR angiography showed no abnormality (data not shown). However, the diagnosis was vague and the patient was transferred to the emergency department of our hospital due to seizures. Anticonvulsants including benzodiazepines and oxcarbazepine were used to control the seizures. The recurrent abdominal pain and seizures gave us reason to suspect of AIP, given the prognosis from case 1. She had no family history of similar symptomatology or other particularly notable medical history. At the time of admission, her blood pressure was 136/101 mm Hg, and her heart rate was 109/min. The general physical examination was normal and there was no focal neurological deficit. On the night of admission, the patient had hallucination. Except for remarkable hyponatremia of 104 mmol/L, her serum potassium was 3.0 mmol/L, aspartate transaminase 243 U/L, alanine transaminase 142 U/L, and total bilirubin 37 μmol/L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero-negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid (CSF) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution (Fig. 4 ). AIP was confirmed by 3 repeated urine Watson–Schwartz tests. The patient was given a high carbohydrate diet and intravenous dextrose. No hematin was available for her, but her status improved gradually when she was discharged. No seizures occurred, and her abdominal pain regressed. Two weeks later, a repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions (Fig. 5 ). One month later, she recovered completely and went back to work. No acute attacks have occurred to date. Because this was cases report without any research involving human beings or experimental subjects, the ethical approval was not required in our institute. But patients have provided informed consent for publication of the case.', 'Case presentation:': \"Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson–Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up.\", 'Case 1': 'In December 2014, a 27-year-old man was admitted to our hospital for abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week. He was diagnosed with acute pancreatitis with mild elevated urine amylase in his local hospital. No abnormalities were found in his abdominal computed tomography (CT) and X-ray. However, the paroxysmal pain was not relieved, and his blood pressure increased. Six days later, a generalized tonic-clonic seizure occurred. Then, partial seizures in the left limb continued. He was transferred to our hospital. No particular medical or family history was reported. At the time of admission, he described recurrent severe paroxysmal abdominal and lumbar pain. His clinical examination was unremarkable, except for decreased tendon reflex in the 4 limbs. There was no complaint of visual disturbance. The patient had moderately increased blood pressure (159/101 mm Hg) and tachycardia (112/min). His creatine kinase was 246 U/L (normal, 0–170 U/L), aspartate transaminase was 42 U/L (15–40 U/L) and serum sodium was 130 mmol/L (normal, 137–147 mmol/L). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1-weighted images and were hyperintense on T2-weighted and fluid-attenuated inversion recovery images. Diffusion-weighted images (DWI) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient (ADC) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES (Fig. 1 ). There was mild contrast enhancement (data not shown). Electroencephalography showed diffuse slow waves without epileptiform discharges. The results of the cerebrospinal fluid analysis were normal. His severe recurrent abdominal pain without clear etiology was suspect of AIP. The diagnosis of AIP was made after 3 repeated positive urine Watson–Schwartz tests for porphobilinogen (PBG). His urine turned dark and red upon exposure to light (Fig. 2 ). Glucose infusion and a high carbohydrate diet were given to the patient, as hematin was not available in our hospital. The patient responded well and recovered gradually. He was discharged with no seizure or abdominal pain. Upon review, he remained asymptomatic.'}", "questions": ["What gastrointestinal symptoms, such as abdominal pain, constipation, or other disturbances, were reported in the cases?", "How was the abdominal pain characterized regarding recurrence, severity, and pattern (e.g., recurrent, severe, paroxysmal) for each patient?", "What was the duration of the abdominal and lumbar pain, and were any precipitating factors like heavy food intake or alcohol consumption noted?", "Was pancreatitis diagnosed, and what clinical or laboratory findings supported that diagnosis?", "What changes in the abdominal pain were observed after treatment?", "How was the abdominal pain described in relation to the onset of seizures?"], "ground_truth_arguments": ["ileus", "abdominal pain as well as constipation", "recurrent abdominal pain", "her abdominal pain regressed", "Unexplained abdominal pain", "abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week", "acute pancreatitis", "paroxysmal pain was not relieved", "recurrent severe paroxysmal abdominal and lumbar pain", "severe recurrent abdominal pain"]}
{"id": "CaseReportBench:train-211", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What are the characteristics of the patient's hearing impairment, including when it began and its classification?", "What ocular abnormality was observed on physical examination of the patient?"], "ground_truth_arguments": ["bilateral hearing loss was present since 5 years of age", "proptosis,", "Auditory evaluation revealed bilateral sensorineural hearing loss"]}
{"id": "CaseReportBench:train-461", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case 2': \"A 13-year-old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks. On examination, there were severe atrophic scars on the face and exposed parts of the extremities, which had resulted in mutilating deformities of the fingers. Hypertrichosis, pigmentation, and milia formation were also present on the face. Though erythrodontia was not spotted with the naked eyes, the teeth revealed a pink-red fluorescence under Wood's lamp. Histopathological examination of an intact bulla revealed the subepidermal location of the blister. A clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity, blistering, and hypertrichosis. The early onset and the mutilation of the fingers were highly suggestive of CEP. The patient was investigated. Routine investigations, including liver and renal function tests, were within normal limits except for mild anemia (Hb 8.0 g/dl, reticulocyte count 7% of circulating erythrocytes). ELISA for HIV was negative. PBG was normal in urine. On screening with a spectrophotometer, urinary total porphyrin was 1187 nmol/mmol of creatinine (normal <35 nmol/mmol). Twenty-four-hour urinary levels of uroporphyrin and coproporphyrin were raised. The erythrocytic porphyrins showed a level of 124.3 μg/100 ml (reference value less than 40 μg/100 ml using the hematofluorometric method). A diagnosis of CEP was made.\", 'Case 1': \"A 3-year-old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks. On examination, the child's face was badly scarred. There was hypertrichosis on the shoulders, arms, and face. The teeth were of coppery-red color. There were a few intact blisters and crusted lesions on the hands and feet. Atrophic scars were also present on the extremities. On the basis of the history of blistering on the exposed areas since early infancy, healing with atrophic scarring, erythrodontia, and red-colored urine, we made a clinical diagnosis of CEP. Routine investigations were within normal limits except for mild anemia. The urine did not show increased level of porphobilinogen (PBG). Further investigations were not carried out. The child was treated symptomatically.\"}", "questions": ["What is the patient’s age at presentation and does the history mention consanguineous parents?", "Summarize the onset age, typical distribution (e.g., exposed areas), and healing pattern of the photosensitivity‑related blisters.", "What urine coloration abnormalities, if any, are described in the case?", "If the document reports it, state the patient’s mental and physical developmental status.", "Is there any family history of similar blistering or photosensitivity conditions?", "Is there any history of acute neurological attacks?"], "ground_truth_arguments": ["A 13 - year - old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks", "A 3 - year - old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child 's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks."]}
{"id": "CaseReportBench:train-177", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}", "questions": ["What are the patient's height, weight, and body mass index (BMI) as reported in the case description?"], "ground_truth_arguments": ["height 149.0 cm, weight 39.2 kg, BMI 17.7 kg / m 2"]}
{"id": "CaseReportBench:train-58", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': \"A 3-yr-old boy was admitted because of eczema, recurrent infection, and thrombocytopenia with a platelet count less than 10×10 9 /L and was diagnosed as having WAS with a large deletion in the exon 1 to 11 of the WAS gene ( Fig. 1 ). For the detection of mutation, the following primers were used; exon 1 forward 5'-GGT TTT TTG CAT TTC CTG TTC-3' and exon 1 reverse 5'-AGG AAG AGG AAG AAA CGG TG-3', exon 2 forward 5'-CCT GAC CAG ACT CCA CTG AC-3' and exon 2 reverse 5'-CTT GAA GCT ATG GAC ACA TAT G-3', exon 3 forward 5'CCT CAG TGC CAC TGT GCC TC3' and exon 3 reverse 5'-TTC CCA TCT CCT CTC CAC AC-3', exon 4 forward 5'-GTG TGG AGA GGA GAT GGG AA-3' and exon 4 reverse 5'-CAC TCA CCT CTG CCC AAC TT-3', exon 5 forward 5'-AAG TTG GGC AGA GGT GAG TG-3' and exon 5 reverse 5'-AGA GAG TTA TCA CAG CCC TG-3', exon 6 forward 5'-GGC TGT GAT AAC TCT CTA CA-3' and exon 6 reverse 5'-CCA TCC ATC CAG AGA CAC AG-3', exon 7 forward 5'-TGG TAA GTG GGT CAA TGA GC-3' and exon 7 reverse 5'-CAG CTG TCC ACT TGT TCA TG-3', exon 8 forward 5'-AAG GAA GGG CAG TGA GGA TT-3'and exon 8 reverse 5'-GGT GGA AGT TTA GTG GAG TC-3', exon 9 forward 5'-CGC CTT ATT CCT CTA CTC CT-3'and exon 9 reverse 5'-GAC TGA GTG ACT TAG TGC GT-3', exon 10-1 forward 5'-TCA GTC AGG AGT TGG TCA GT-3'and exon 10-1 reverse 5'-GTC CAG AAC GTC CAG TAG CT-3', exon 10-2 forward 5'-CAG CTA CTG GAC GTT CTG GA-3'and exon 10-2 reverse 5'-CAG TAT CCT GAC TTA GAC GG-3', exon 11 forward 5'-GAG AAA TGC TCC TTT CCC AG-3'and exon 11 reverse 5'-TAG CCC TGG GAG CCA GGT TT-3', exon 12 forward 5'-CTC CCA GGG CAT CTT ATC TT-3'and exon 12 reverse 5'-AGC ACA GGG CAG CAA GTA AC-3'. He received transplantation from an HLA-A, B, C, DR, and DQ-matched unrelated male donor confirmed by a high-resolution molecular method, after the conditioning regimen composed of fludarabine (40 mg/m 2 on days -8, -7, -6, -5, -4, -3), busulfan (0.8 mg/kg i.v. q 6 hr on days -6, -5, -4, -3), and thymoglobulin (2.5 mg/kg on days -4, -3, -2). Written informed consent was obtained from parents of the patient before transplantation. Graft versus host disease (GVHD) prophylaxis was composed of cyclosporin, methotrexate (15 mg/kg on day 1, 10 mg/kg on days 3 and 6), and thymoglobulin (1.25 mg/kg on days 7, 9, 11). Other supportive care was performed according to the guideline for stem cell transplantation of our center ( 6 ). The number of infused nucleated cells and CD34-positive cells were 7.6×10 8 /kg and 6.2×10 6 /kg, respectively. He received G-CSF from 7 days after stem cell infusion and the nadir of white blood cells (0.09×10 9 /L) occurred 12 days after transplantation. The number of days required for absolute neutrophil count of more than 0.5×10 9 /L and 1.0× 10 9 /L were 14 days and 15 days, respectively, and spontaneous platelet recovery to more than 20×10 9 /L and 100× 10 9 /L required 16 days and 43 days, respectively. Grade I hematuria, grade II proteinuria, and grade II hepatic toxicity occurred during the transplantation but recovered spontaneously. No other serious complications occurred during transplantation. Grade II acute GVHD occurred 17 days after transplantation but resolved after the treatment with steroid. Bone marrow examination performed at one month post-transplantation revealed the donor type chimerism at 98.4% analyzed by short tandem repeat analysis and the normal polymerase chain reaction pattern in exons of the WAS gene ( Fig. 1 ). After 3 months of transplantation, complete donor type chimerism was achieved. Post-transplatation lymphoproliferative disease occurred 4 months after BMT but completely resolved with rituximab therapy. Chronic GVHD did not occur, and he is alive at 16 months after transplantation without any disease characteristics of WAS.\"}", "questions": ["What category of mutation is reported for the WAS gene, and which part of the gene is affected?"], "ground_truth_arguments": ["WAS with a large deletion in the exon 1 to 11 of the WAS gene"]}
{"id": "CaseReportBench:train-506", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case Description': 'Polyhydramnios in the second and third trimester of pregnancy is defined by (semiquantative) measurements such as a maximum vertical pocket (MVP) >8 cm, or an amniotic fluid index (AFI) >24 cm. Approximately 90% of cases are idiopathic or caused by gestational diabetes (GDM) 1 . However, 10% of cases are associated with fetal structural abnormalities 2 . Most frequent causes are impaired swallowing from any cause (gastrointestinal, facial, musculoskeletal, or brain abnormalities), cardiac failure, hydrops, and renal abnormalities. Metabolic diseases, such as congenital disorders of glycogen storage, are also incidentally reported to present with polyhydramnios in pregnancy 3 . The usual diagnostic work‐up of polyhydramnios is to exclude GDM and maternal infections, and to perform an extensive structural assessment to rule out fetal anomalies. The presence of structural anomalies, involves increased risk of aneuploidy or other chromosomal and syndromic disorders. In isolated polyhydramnios, the risk of perinatal adverse outcome is, however, still increased when compared with uneventful pregnancies 4 . A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios. Aside from a spontaneously closed ventricular septal defect (VSD) in her own infancy, both parents were healthy. A maternal uncle of the mother had died postnatally of an unknown cause. First‐trimester combined test revealed a low risk for trisomies (NT 1.1 mm). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios (uterine size that outpaced gestational age) and premature contractions. She received tocolytics and corticosteroids for fetal lung maturation. Ultrasound showed polyhydramnios (MVP 9.9 cm, AFI 27.5 cm) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles (11 mm). Amniotic fluid drainage (1.8 L) was performed in an attempt to cease the premature contractions. More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna (12 mm) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm (slightly below p3, with head circumference p50, Fig. 1 A). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD. QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 (11q22.1), including exon 1 of the contactine 5 ( CNTN5 ) gene. This variant is not reported as genomic variant in the normal population, neither known to be associated with a genetic disorder or malformation. A relation with the clinical signs appears unlikely. Maternal serum infection testing (TORCHES) was also normal. Two days later (26 + 0), she spontaneously delivered a boy of 835 g (−0.5 SDS), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively. At birth, he was started on CPAP and transported to the neonatal intensive care unit. Physical examination showed a hypotonic infant with a lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus (Fig. 1 B). He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges. The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels. Testes were not palpable in the scrotum. Postnatal cardiac ultrasound confirmed the presence of a small VSD. Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy. A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome. He developed hypotension and was treated with fluid boluses and inotropic support and antibiotics. Despite stabilization of blood pressure and systemic circulation, he developed a progressive lactate acidosis with extremely high plasma lactate: 19.1 mmol/L and high pyruvate: 269 μ mol/L. The L/P (lactate/pyruvate) ratio was 71, which is strongly increased (normal <20). Organic acid analysis in urine showed a strong increase of lactate (56540 μ mol/mmol creatinine) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal. In the absence of secondary causes, these findings are consistent with primary lactic acidosis, caused by a disorder of the pyruvate metabolism or a mitochondrial respiratory chain defect. Due to the severity of the cumulative problems, the neonate died 2 days after birth. Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst (Figure S1C), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst (Figure S1D). DNA analysis of the PDHA1 ‐gene (most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency) showed no pathogenic mutations. Large deletions, point mutations, and small insertions/deletions in mitochondrial DNA (mtDNA) derived from blood were excluded by next‐generation sequencing (NGS) using the Illumina MiSeq platform and a dedicated bioinformatics pipeline (available on request). For whole exome sequencing, exome enrichment was performed by the Agilent SureSelectXT exome enrichment kit version 4, including the UTR regions. Sequencing was performed by an Illumina HiSeq2000 (San Diego, CA) using a 2 × 100 bp paired‐end recipe. Basecalling, and demultiplexing was done using bcl2fastq 1.8.4.,(Illumina, San Diego, CA) reads were aligned onto the human reference genome (hg19) using BWA 0.5.9., duplicates marked using the PICARD software suite 1.77 (GitHub Enterprise, San Francisco, CA), and variants were called using GATK 2.1‐8. Annotations were added using an in‐house build annotation database, according to UCSC RefGene track, dbSNP137, and the dbNSFP (v2.0). Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing: c.292C>T (p.(Arg98*))and c.1303C>T (p.(Arg435*)). Both are nonsense mutations resulting in a premature stop codon at position p.98 and p.435 of the FBXL4 protein, respectively. The location of these mutations on different alleles (compound heterozygosity) was confirmed by testing the parents. Missense and stop mutations in the FBXL4 gene were reported recently to be associated with severe autosomal recessively inherited mitochondrial encephalomyopathy 5, 6, 7, 8 . Our case is the first case demonstrating a premature prenatal onset of symptoms of FBXL4‐ related mitochondrial encephalomyopathy. The polyhydramnios was the primary sign, leading to the detection of brain abnormalities on more detailed fetal ultrasound examination. This early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements. The cases of FBXL4 ‐related encephalopathy reported so far are characterized by increased serum lactate level, psychomotor delay, hypotonia, failure to thrive, swallowing difficulty, and muscle wasting 6 . Onset of symptoms varied from neonatal onset after term birth, to the age of 14 months 5, 6, 8 . Other reported cases were born at term or premature due to medical intervention for intrauterine growth retardation or reduced fetal movements 5, 6 . The FBXL4 gene is situated on nuclear DNA on chromosome 6q16.1. The FBXL4 mitochondrial protein contains an F‐box in its N‐terminal half, followed by 11 leucine‐rich repeats 9, and is expressed in heart, kidney, liver, lung, pancreas, and placenta 10 . Evidence of the pathogenetic effect of FBXL4 mutations was provided by skeletal muscle biopsies and fibroblasts showing defects in mitochondrial respiratory chain enzyme activities, loss of mitochondrial membrane potential, a disturbance of the dynamic mitochondrial network, and mtDNA depletion 5 . The nonsense mutation p.Arg435* in the FBXL4 gene, present in our patient, was earlier reported in homozygous form in a child of consanguineous parents with early onset mitochondrial encephalopathy, severe hypotonia, cardiomyopathy, MRI abnormalities, increased serum lactate, and premature death 5 . The second mutation detected in our patient (p.Arg98* mutation) has not been reported previously. However, like the other mutation reported, this nonsense mutation leads to nonsense‐mediated decay (NMD, RNA degradation) or a truncated protein 5, 6 . As a result, our patient would have been unable to produce a normal FBXL4 gene product. The mother was pregnant again before exome sequencing had started. Within the prenatal timeframe, exome sequencing lead to the diagnosis of the first child, consequently enabling prenatal diagnosis for the second child. Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child. The VSD in our patient is considered to be a separate finding (familial trait), which is not related to the syndrome. Our case demonstrated a prenatal onset of mitochondrial encephalomyopathy presenting with polyhydramnios, causing premature delivery, and cerebellar atrophy. The neonate was hypotonic and in a poor condition with need for mechanical ventilation, inotropic support, and persistent lactate acidosis. Targeted exome sequencing using a mitochondrial gene panel proved its benefit by revealing compound heterozygous mutations in the FBXL4 gene. Prenatal testing was successfully carried out in the current pregnancy. Direct testing for mutations in the FBXL4 gene should be considered in patients with severe encephalomyopathy with high levels of serum lactate.'}", "questions": ["Describe the findings related to the infant's testes on physical examination."], "ground_truth_arguments": ["Testes were not palpable in the scrotum"]}
{"id": "CaseReportBench:train-591", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 12-year-old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days. On physical examination the child was found to have retarded growth (dwarfism) and a pendulous abdomen. Per abdominal examination revealed hepatomegaly. USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm–sized, well-defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well-circumscribed, low-attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted. Hepatomegaly with diffusely low attenuation of liver, bilateral renal calculi (which hinted at hyperuricemia – a known feature of von Gierke disease), clinical features of dwarfism, facial dysmorphism, and protuberant abdomen, were all features that favored the diagnosis of von Gierke disease. Moreover, in the pediatric age-group, liver tumors are rare and hepatic adenoma occurs almost exclusively in patients with underlying von Gierke disease. CT scan features like well-circumscribed margins, subcapsular location, and contrast enhancement also supported the diagnosis of hepatic adenoma. Based on these CT scan findings and clinical features, a probable diagnosis of hepatic adenoma in a case of type Ia glycogen storage disease (von Gierke disease) was suggested. Preoperative laboratory evaluation revealed increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits. The patient was operated and the mass in the liver was surgically resected. The specimen was sent for histopathological examination along with a small bit of liver tissue, which showed PAS-positive glycogen-rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma.'}", "questions": ["What was the patient's age at presentation (in years)?"], "ground_truth_arguments": ["12 - year - old"]}
{"id": "CaseReportBench:train-319", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Description': 'The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like “X”-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS).', 'Case presentation': 'A 32-year-old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient’s visit to our hospital. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Oral informed consent was obtained from the patient. On the patient’s maternal side, there was a history of rectal cancer (the patient’s grandmother, an uncle, and an aunt), uterine cancer (a 29-year-old female cousin), rectal cancer with uterine cancer (two aunts), and colon polyposis (a 29-year-old male cousin) ( Figure 1A ). A physical examination showed mild tenderness only in the right lower abdomen. No significant abnormalities were found in serum tumor markers. A colonoscopy revealed a cauliflower-like mass at the beginning of the ascending colon ( Figure 1B ). Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast-enhanced computed tomography (CT) showed ascending colon cancer with intussusception ( Figure 1D ). The preoperative diagnosis was cT3N0M0 colon cancer, according to the TNM classification. On August 27, 2021, the patient underwent laparoscopic radical right hemicolectomy under general anesthesia. During the operation, we found that there were two ICAs derived from the SMA, with the ileocolic vein (ICV) crossing anterior to the SMA ( Figure 2A ). The right colic vein was also absent ( Figure 2B ). The gastrocolic trunk of Henle was draining into the superior mesenteric vein (SMV), which was joined by the right gastroepiploic and colic veins, the anterior superior pancreaticoduodenal vein, and the superior right colic vein ( Figure 2C ). Furthermore, the SMA and SMV were found to be accompanied like “X”-shaped variant ( Figure 2D ). As we saw in the surgery，abdominal contrast-enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery (RCA) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C ). We summarized the schematic diagram of vascular variation of this patient ( Figure 3D ). The patient was discharged on the fourth day after surgery. Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient’s tumor sample ( Figure 5C,5D ). Given the patient’s family history of cancer, we highly suspected Lynch syndrome (LS). Next-generation sequencing (NGS), performed by 3D Medicines Inc. (Shanghai, China), was used to analyze tumor and blood samples from the patient. As shown in Figure 6, the results revealed MLH1 c.885-1_893del, which may represent a change in the conformation of the acceptor splicing site, which may have impeded mRNA formation, eventually leading to deficient mismatch repair. Seven weeks after surgery, the patient was administered a regimen of adjuvant chemotherapy with CapeOX (day 1, oxaliplatin 130 mg/m 2, day 1 to 14 capecitabine 1,000 mg/m 2, po, twice a day, every 3 weeks) for four cycles. Four months after the end of chemotherapy, CT reexamination showed no tumor recurrence ( Figure 7 ).'}", "questions": ["What type of tumor was identified and what was its AJCC stage?", "Based on the family cancer history and molecular testing results, what hereditary cancer predisposition could be considered?"], "ground_truth_arguments": ["The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon . Given the patient ’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next - generation sequencing , we concluded that she had Lynch syndrome ( LS"]}
{"id": "CaseReportBench:train-323", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case report': 'Phenotypic female twins (A, B) were born at 36+2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g (<10 percentile) in A and 2,040 g (10 to 25 percentile) in B, height was 43 cm (10 to 25 percentile) in A and 44 cm (10 to 25 percentile) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit (NICU). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17-OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17-OHP, elevated ACTH (A, 4,379.2 pg/mL at 23 days of life; B, 11,616.1 pg/mL at 29 days of life), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng/mL/hr). However, the level of plasma cortisol before treatment were normal (8.71 µg/dL initially, 7.11 µg/dL in 2nd sample) in patient A, but low (1.5 µg/dL) in patient B. The results of endocrinologic investigation are shown in Table 1 . The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography (CT) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level (132 to 139 mmol/L) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia (129 to 133 mmo/L) and further evaluation for skin hyperpigmentation. She was treated with oral supplementation of sodium (0.8 to 0.9 mmol/kg) at 11 to 35 days of age, and she discharged from the hospital with normal sodium level after tapering off sodium supplementation at 37 days of age. Patient A was admitted at 38 days of age with adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration. Clinical findings of patient A were suggestive of CLAH and prompted us to order a gene analysis in both twins. Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C>T (p.R182C) in exon 5 and c.722C>T (p.Q258X) in exon 7 ( Fig. 1 ). Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms, except hyponatremia, but she was also diagnosed with CLAH with the same StAR gene mutation with patient A. The results of gene analysis of parents showed heterozygous for the mutations in the StAR gene; the heterozygous gene mutations; c.772C>T in the mother, and c.544C>T in the father, were documented. They showed suboptimal levels of hormone despite of administration of 20 mg/m 2 /24-hr of hydrocortisone, dose of hydrocortisone was increased up to 30 mg/m 2 /24-hr. Both patients have been under steroid supplementation (fludrocortisones 0.2 mg daily in 2 divided doses, and hydrocortisone 12 mg daily in 3 divided doses) at 14 months of age. They showed normal development except retarded physical growth, and hormones and electrolyte levels on follow up are shown as Table 1 . Body weight was 8.8 kg (3 to 10 percentile) in patient A, 9.4 kg (10 to 25 percentile) in patient B, body length was 73.7 cm (3 to 10 percentile) in patient A, 75.4 cm (10 to 25 percentile) in patient B at 14 months of age. They had been regularly followed.'}", "questions": ["What are the patients' body weights (in kilograms) and the associated growth percentiles at 14 months of age?", "What are the patients' body lengths (in centimeters) and the associated growth percentiles at 14 months of age?"], "ground_truth_arguments": ["Body weight was 8.8 kg ( 3 to 10 percentile ) in patient A, 9.4 kg ( 10 to 25 percentile ) in patient B, body length was 73.7 cm ( 3 to 10 percentile ) in patient A, 75.4 cm ( 10 to 25 percentile ) in patient B at 14 months of age."]}
{"id": "CaseReportBench:train-70", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}", "questions": ["Which medications were administered specifically as therapy for the acute porphyria episode?", "What was the patient’s overall clinical outcome after receiving the porphyria‑specific treatments?"], "ground_truth_arguments": ["she was given haem arginate , glucose and symptomatic drugs , and she recovered completely", "she was given haemarginate , glucose"]}
{"id": "CaseReportBench:train-498", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}", "questions": ["What fertility problems did the patient have at presentation, and what were the results of the initial semen analysis?", "When were the bilateral testicular adrenal rest tumors first identified, and how would you describe their size relative to the testes?", "What findings were reported on the most recent ultrasound regarding the TARTs' size and their proportion of the total testicular volume?", "After adjusting glucocorticoid therapy, what changes were observed in the total TART volume, and what were the main results of the follow‑up semen analysis?", "What were the reported testicular volumes at baseline and at follow‑up, and did they change over the follow‑up period?"], "ground_truth_arguments": ["subfertility", "bilateral TARTs, first noted at age 18 and occupying 1.2 % of his total testicular volume ( 0.38 mL of 30.68 mL )", "A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.", "Testicular volume was 25 mL bilaterally", "Testicular volume was stable at 25 mL.", "91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % )."]}
{"id": "CaseReportBench:train-566", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Chief complaints': 'Recurrence of abdominal pain, nausea, and vomiting in a kidney transplant patient.', 'Personal and family history': 'The patient had no known family history of porphyria.', 'CASE SUMMARY': 'The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro-pathy. He subsequently developed diabetes mellitus which required insulin therapy. He had been treated in the recent past with local mesalamine for proctitis. He presented with classic but common symptoms of AIP including intense abdominal pain, hypertension, and anxiety. He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained. His urinary postprandial blood glucose level was 60 mg/24 h (normal, < 2 mg/24 h). He was placed on a high carbohydrate diet, and his symptoms slowly improved.', 'Physical examination': 'The patient was hemodynamically stable with a heart rate of 90 bpm and blood pressure of 160/90 mmHg, but appeared in mild distress. The physical examination revealed an intermittently tender, non-distended abdomen with normal bowel sounds and absent rigidity, rebound, and guarding. The remainder of the physical exami-nation was unremarkable.', 'Imaging examinations': 'Plain X-rays of the abdomen showed distended colon and fecal impaction, and ultrasound revealed that the liver, spleen, pancreas, and transplanted kidney were of normal size and consistency and that the site of the left nephrectomy was occupied by intestinal loops.', 'Laboratory examinations': 'Serum levels of hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C-reactive protein were normal, as was the urine analysis. Renal function was stable with a serum creatinine of 1.2 mg/dL; the urine culture was negative.', 'History of present illness': 'A 65-year-old man reported the appearance of rectal blood in March 2017 and visited a proctologist. He started local mesalamine therapy for proctitis, but the drug was discontinued a few days later due to abdominal pain and constipation. During the subsequent 6 mo, he presented several times to the emergency department complaining of severe abdominal pain, nausea, and vomiting. He related an anxious mood and low energy level in addition to tachycardia and an increase in blood pressure which was no longer well-controlled with his usual therapy. He presented to the emergency room eight times for various complaints (Figure 1 ): Epigastric pain without mention of mesalamine, agitation and anxiety, thoracic pain, abdominal pain, and precordial pain.', 'History of past illness': 'The patient had been treated for hypertension since 1994 and developed ischemic heart disease. His renal function gradually deteriorated over the years due to suspected nephroangiosclerosis and chronic interstitial nephropathy, as ultrasound examination demonstrated small echogenic kidneys. He started hemodialysis in 2008 and was evaluated for renal transplantation; a left nephrectomy was performed for a small incidental renal carcinoma. The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis. He underwent a deceased-donor kidney transplant in 2015, for which he was treated with tacrolimus, mycophenolate mofetil, and methylprednisolone. He developed diabetes mellitus post-transplant and insulin therapy was initiated (see Table 1 ).'}", "questions": ["What gastrointestinal symptoms recurred in the kidney transplant patient?", "What is the patient's family history concerning porphyria?", "When did the patient receive the kidney transplant and what were the primary renal diagnoses that led to transplantation?", "What was the source of the kidney donor and approximately when was the transplant performed?", "What long‑term cardiovascular conditions has the patient been treated for since 1994?", "What surgical procedure was performed on the left kidney and what pathology was identified?", "What metabolic disorder developed in the patient after the kidney transplant?"], "ground_truth_arguments": ["Recurrence of abdominal pain, nausea, and vomiting in a kidney transplant patient", "The patient had no known family history of porphyria", "transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro - pathy", "treated for hypertension since 1994 and developed ischemic heart disease", "a left nephrectomy was performed for a small incidental renal carcinoma", "deceased - donor kidney transplant in 2015", "diabetes mellitus post - transplant"]}
{"id": "CaseReportBench:train-520", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["What recent neurological symptoms did the patient experience, including any seizures and limb weakness?", "What was the patient's level of consciousness and what were the main findings on motor examination, such as muscle strength and reflexes?", "What were the findings of the electroencephalography performed on the patient?", "What were the results of the cerebrospinal fluid analysis?", "What did the nerve conduction study reveal about the nature of the neuropathy?"], "ground_truth_arguments": ["history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness", "conscious ( E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent", "electroencephalography were normal.", "Cerebrospinal fluid analysis was normal.", "Nerve conduction study showed axonal motor neuropathy"]}
{"id": "CaseReportBench:train-64", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case report': 'A 2-year-old boy was referred to our hospital due to developmental delay, ichthyosis, asthma, and recurrent pneumonia. His parents were related but there was no history of asthma, and allergic disorders in his family, and close relatives. He had ichthyosis at birth, and mild intermittent asthma, and 2 episodes of pneumonia also were observed in his first year of life. He had no history of seizure. His physical examination revealed spastic diplegia and brisk deep tendon reflexes in lower limbs. He was not able to stand or walk, independently and his speech was limited to 2–3 meaningful words. Acquisition of other developmental skills was mildly delayed with achieving head control and sitting without support at 5 and 12 months, respectively. Extensive hyperkeratosis and scaling of the skin were seen particularly in the dorsum of hands, skin flexures, and lower abdomen ( Fig. 1 ). Funduscopic examination was normal. Electroencephalography, routine laboratory tests, and chromosomal study were also normal. Magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the deep white matter around the trigons of lateral ventricles ( Fig. 2 ). Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging and parakeratosis consistent with ichthyosis. Molecular genetics study utilizing sequencing of the polymerase chain reaction product using the exon-specific primers revealed a c.370-372 (GGA) deletion mutation in the second exon of ALDH3A2 gene in a homozygote state. Therefore, the diagnosis of SLS was confirmed. The patient was treated, symptomatically with inhaled corticosteroid, and bronchodilator, local paraffin applicants, and rehabilitation therapy.'}", "questions": ["What were the findings of the funduscopic examination?"], "ground_truth_arguments": ["Funduscopic examination was normal"]}
{"id": "CaseReportBench:train-493", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["What chromosomal or genetic syndrome is diagnosed in the patient?", "Which neurocutaneous disorders are identified in the patient?"], "ground_truth_arguments": ["Turner syndrome ( TS ) patient with Neurofibromatosis 1 ( NF1 ) and Tuberous sclerosis complex ( TSC )"]}
{"id": "CaseReportBench:train-191", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case 5': 'A 62-year-old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5-year history of an asymptomatic eruption on the neck. Physical examination revealed numerous soft, oval-to-round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area. Echocardiography was unremarkable. The ophthalmologic examination was normal. Moreover, no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption.', 'Histopathology of cases (1–3)': 'A skin punch biopsy was performed, and the hematoxylin and eosin (H and E) sections revealed a normal-appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.', 'Histopathology of case 4 and 5': 'H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident.', 'Case 3': \"A 68-year-old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years. Physical examination revealed numerous tan to yellowish soft papules over the lateral side of the patient's neck, measuring 2–3 mm. The patient had no systemic symptoms and was otherwise healthy.\", 'Case 4': \"A 61-year-old female patient presented to the clinic with a 2-year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis. On physical examination, there were multiple symmetrically distributed, skin-colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient's neck, upper chest, and the antecubital fossa of both forearms. There was no history of sun exposure or family history of similar cutaneous manifestation.\", 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Case 2': \"A 77-year-old female presented with a 4-year history of gradual appearance of small skin-colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension. However, other systemic examinations were unremarkable, especially for eye, cardiac, or gastrointestinal systems.\", 'Case 1': 'A 71-year-old female presented with a 1–2-year history of asymptomatic skin-colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints. Given the clinical resemblance to PXE, an ophthalmology consult was performed to rule out the presence of angioid streaks. The eye examination was normal.'}", "questions": ["For each case, specify the symptom status of the skin lesions (e.g., asymptomatic, itchy) and enumerate all anatomical locations where lesions are observed.", "Describe the papules in each case, including their color, consistency, shape, size range, and whether their distribution is symmetric or localized.", "Report any overall lesion patterns mentioned (e.g., cobblestone appearance, coalescence into plaques) and indicate whether lesions are confined to the neck or involve additional body sites.", "Summarize the histopathological findings for each case, covering epidermal appearance, dermal characteristics, elastin‑stain results (presence/absence and morphology of elastic fibers in papillary, reticular, mid, and deep dermis) and the presence or absence of calcification.", "Identify any cases with a progressive itchy reaction triggered by an external factor, describing the trigger and the nature of the reaction.", "List any autoimmune or inflammatory dermatologic conditions (e.g., psoriasis, lupus) reported in the patients' past medical histories."], "ground_truth_arguments": ["asymptomatic eruption on the neck.", "numerous soft, oval - to - round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area", "A skin punch biopsy was performed, and the hematoxylin and eosin ( H and E ) sections revealed a normal - appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.", "H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident", "asymptomatic cutaneous lesions", "numerous tan to yellowish soft papules over the lateral side of the patient 's neck, measuring 2–3 mm", "slowly progressive itchy skin lesions after spraying perfumes.", "multiple symmetrically distributed, skin - colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient 's neck, upper chest, and the antecubital fossa of both forearms", "gradual appearance of small skin - colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient 's neck and the upper chest bilaterally.", "psoriasis", "asymptomatic skin - colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved."]}
{"id": "CaseReportBench:train-121", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Which body regions showed hyperpigmentation and skin thickening, and how were these changes characterized?", "What ocular and cervical abnormalities were observed in the patient?", "How are the hyperpigmented indurated plaques described regarding their morphology, symmetry, distribution, and any associated hair changes?", "What histopathological findings were reported on the skin biopsy?"], "ground_truth_arguments": ["hyperpigmentation over the thighs", "skin thickening over the buttocks, thighs, and legs", "proptosis, webbing of neck", "well - defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally", "Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate"]}
{"id": "CaseReportBench:train-264", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Description': 'Polyhydramnios in the second and third trimester of pregnancy is defined by (semiquantative) measurements such as a maximum vertical pocket (MVP) >8 cm, or an amniotic fluid index (AFI) >24 cm. Approximately 90% of cases are idiopathic or caused by gestational diabetes (GDM) 1 . However, 10% of cases are associated with fetal structural abnormalities 2 . Most frequent causes are impaired swallowing from any cause (gastrointestinal, facial, musculoskeletal, or brain abnormalities), cardiac failure, hydrops, and renal abnormalities. Metabolic diseases, such as congenital disorders of glycogen storage, are also incidentally reported to present with polyhydramnios in pregnancy 3 . The usual diagnostic work‐up of polyhydramnios is to exclude GDM and maternal infections, and to perform an extensive structural assessment to rule out fetal anomalies. The presence of structural anomalies, involves increased risk of aneuploidy or other chromosomal and syndromic disorders. In isolated polyhydramnios, the risk of perinatal adverse outcome is, however, still increased when compared with uneventful pregnancies 4 . A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios. Aside from a spontaneously closed ventricular septal defect (VSD) in her own infancy, both parents were healthy. A maternal uncle of the mother had died postnatally of an unknown cause. First‐trimester combined test revealed a low risk for trisomies (NT 1.1 mm). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios (uterine size that outpaced gestational age) and premature contractions. She received tocolytics and corticosteroids for fetal lung maturation. Ultrasound showed polyhydramnios (MVP 9.9 cm, AFI 27.5 cm) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles (11 mm). Amniotic fluid drainage (1.8 L) was performed in an attempt to cease the premature contractions. More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna (12 mm) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm (slightly below p3, with head circumference p50, Fig. 1 A). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD. QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 (11q22.1), including exon 1 of the contactine 5 ( CNTN5 ) gene. This variant is not reported as genomic variant in the normal population, neither known to be associated with a genetic disorder or malformation. A relation with the clinical signs appears unlikely. Maternal serum infection testing (TORCHES) was also normal. Two days later (26 + 0), she spontaneously delivered a boy of 835 g (−0.5 SDS), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively. At birth, he was started on CPAP and transported to the neonatal intensive care unit. Physical examination showed a hypotonic infant with a lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus (Fig. 1 B). He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges. The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels. Testes were not palpable in the scrotum. Postnatal cardiac ultrasound confirmed the presence of a small VSD. Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy. A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome. He developed hypotension and was treated with fluid boluses and inotropic support and antibiotics. Despite stabilization of blood pressure and systemic circulation, he developed a progressive lactate acidosis with extremely high plasma lactate: 19.1 mmol/L and high pyruvate: 269 μ mol/L. The L/P (lactate/pyruvate) ratio was 71, which is strongly increased (normal <20). Organic acid analysis in urine showed a strong increase of lactate (56540 μ mol/mmol creatinine) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal. In the absence of secondary causes, these findings are consistent with primary lactic acidosis, caused by a disorder of the pyruvate metabolism or a mitochondrial respiratory chain defect. Due to the severity of the cumulative problems, the neonate died 2 days after birth. Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst (Figure S1C), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst (Figure S1D). DNA analysis of the PDHA1 ‐gene (most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency) showed no pathogenic mutations. Large deletions, point mutations, and small insertions/deletions in mitochondrial DNA (mtDNA) derived from blood were excluded by next‐generation sequencing (NGS) using the Illumina MiSeq platform and a dedicated bioinformatics pipeline (available on request). For whole exome sequencing, exome enrichment was performed by the Agilent SureSelectXT exome enrichment kit version 4, including the UTR regions. Sequencing was performed by an Illumina HiSeq2000 (San Diego, CA) using a 2 × 100 bp paired‐end recipe. Basecalling, and demultiplexing was done using bcl2fastq 1.8.4.,(Illumina, San Diego, CA) reads were aligned onto the human reference genome (hg19) using BWA 0.5.9., duplicates marked using the PICARD software suite 1.77 (GitHub Enterprise, San Francisco, CA), and variants were called using GATK 2.1‐8. Annotations were added using an in‐house build annotation database, according to UCSC RefGene track, dbSNP137, and the dbNSFP (v2.0). Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing: c.292C>T (p.(Arg98*))and c.1303C>T (p.(Arg435*)). Both are nonsense mutations resulting in a premature stop codon at position p.98 and p.435 of the FBXL4 protein, respectively. The location of these mutations on different alleles (compound heterozygosity) was confirmed by testing the parents. Missense and stop mutations in the FBXL4 gene were reported recently to be associated with severe autosomal recessively inherited mitochondrial encephalomyopathy 5, 6, 7, 8 . Our case is the first case demonstrating a premature prenatal onset of symptoms of FBXL4‐ related mitochondrial encephalomyopathy. The polyhydramnios was the primary sign, leading to the detection of brain abnormalities on more detailed fetal ultrasound examination. This early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements. The cases of FBXL4 ‐related encephalopathy reported so far are characterized by increased serum lactate level, psychomotor delay, hypotonia, failure to thrive, swallowing difficulty, and muscle wasting 6 . Onset of symptoms varied from neonatal onset after term birth, to the age of 14 months 5, 6, 8 . Other reported cases were born at term or premature due to medical intervention for intrauterine growth retardation or reduced fetal movements 5, 6 . The FBXL4 gene is situated on nuclear DNA on chromosome 6q16.1. The FBXL4 mitochondrial protein contains an F‐box in its N‐terminal half, followed by 11 leucine‐rich repeats 9, and is expressed in heart, kidney, liver, lung, pancreas, and placenta 10 . Evidence of the pathogenetic effect of FBXL4 mutations was provided by skeletal muscle biopsies and fibroblasts showing defects in mitochondrial respiratory chain enzyme activities, loss of mitochondrial membrane potential, a disturbance of the dynamic mitochondrial network, and mtDNA depletion 5 . The nonsense mutation p.Arg435* in the FBXL4 gene, present in our patient, was earlier reported in homozygous form in a child of consanguineous parents with early onset mitochondrial encephalopathy, severe hypotonia, cardiomyopathy, MRI abnormalities, increased serum lactate, and premature death 5 . The second mutation detected in our patient (p.Arg98* mutation) has not been reported previously. However, like the other mutation reported, this nonsense mutation leads to nonsense‐mediated decay (NMD, RNA degradation) or a truncated protein 5, 6 . As a result, our patient would have been unable to produce a normal FBXL4 gene product. The mother was pregnant again before exome sequencing had started. Within the prenatal timeframe, exome sequencing lead to the diagnosis of the first child, consequently enabling prenatal diagnosis for the second child. Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child. The VSD in our patient is considered to be a separate finding (familial trait), which is not related to the syndrome. Our case demonstrated a prenatal onset of mitochondrial encephalomyopathy presenting with polyhydramnios, causing premature delivery, and cerebellar atrophy. The neonate was hypotonic and in a poor condition with need for mechanical ventilation, inotropic support, and persistent lactate acidosis. Targeted exome sequencing using a mitochondrial gene panel proved its benefit by revealing compound heterozygous mutations in the FBXL4 gene. Prenatal testing was successfully carried out in the current pregnancy. Direct testing for mutations in the FBXL4 gene should be considered in patients with severe encephalomyopathy with high levels of serum lactate.'}", "questions": ["What were the findings of the first‑trimester combined test, including nuchal translucency assessment and trisomy risk?", "What did the 20‑week anomaly scan reveal regarding overall fetal anatomy?", "What brain and cardiac abnormalities were identified on the detailed fetal ultrasound performed after amniotic fluid drainage?", "What chromosomal abnormality was detected by QF‑PCR and CytoScan HD Array?", "What were the results of maternal serum infection testing (TORCHES) during the pregnancy?", "What findings were confirmed by postnatal cardiac ultrasound?", "What abnormalities were observed on the first‑day postnatal cranial ultrasound concerning hemorrhages, ventricular dilation, periventricular pseudocysts, and cerebellar structure?", "What laboratory findings demonstrated persistent lactate acidosis?", "What postmortem cranial MRI findings corroborated the earlier imaging results?", "What were the results of DNA analysis of the PDHA1 gene?", "What pathogenic variants were identified by targeted exome sequencing of the mitochondrial gene panel?"], "ground_truth_arguments": ["First‐trimester combined test revealed a low risk for trisomies ( NT 1.1 mm ).", "The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50.", "More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna ( 12 mm ) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm ( slightly below p3, with head circumference p50, Fig. 1 A ). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD", "QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 ( 11q22.1 ), including exon 1 of the contactine 5 ( CNTN5 ) gene.", "Maternal serum infection testing ( TORCHES ) was also normal", "Postnatal cardiac ultrasound confirmed the presence of a small VSD.", "Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy.", "progressive lactate acidosis with extremely high plasma lactate : 19.1 mmol / L and high pyruvate : 269 μ mol / L. The L / P ( lactate / pyruvate ) ratio was 71, which is strongly increased ( normal < 20 ). Organic acid analysis in urine showed a strong increase of lactate ( 56540 μ mol / mmol creatinine ) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal", "Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst ( Figure S1C ), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst ( Figure S1D )", "DNA analysis of the PDHA1 ‐gene ( most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency ) showed no pathogenic mutations", "Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing : c.292C > T ( p.(Arg98*))and c.1303C > T ( p.(Arg435 * ) ).", "brain abnormalities on more detailed fetal ultrasound examination", "persistent lactate acidosis"]}
{"id": "CaseReportBench:train-107", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["Approximately how old was the patient when first referred to the hospital?"], "ground_truth_arguments": ["27 d of age"]}
{"id": "CaseReportBench:train-67", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case Report': \"A 13-year-old male child born off a consanguineous marriage presented with complaints of red colored urine since birth, reddish brown-pigmented teeth, and excessive facial hair since 6 months of age. He also had a burning sensation and recurrent blistering over the sun-exposed areas, which healed with scarring and disfigurement of nails since 1-year of age. His birth and mental developmental history were normal. He had an asymptomatic female sibling 8 years of age, and there was no family history of similar complaints. Examination revealed a short statured male child of height 133 cm (< −3 standard deviations). Abdominal examination revealed a protuberant abdomen with hepatosplenomegaly and undescended testis on the left side. He had obvious hypertrichosis over face involving the cheek and forehead, the forearms and multiple bullae over the dorsum of hands, fingers, forearms, and feet with postinflammatory hyperpigmentation and scars over affected skin. Teeth showed brownish-red pigmentation, fluorescent under Wood's lamp. Nails were discolored. Investigations revealed anemia an Hb of 8.3 g/dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis. Urine was port wine color, which fluoresced in Wood's lamp. Porphobilinogen was not detected on Watson–Schwartz test in the urine. Ultrasonography of abdomen confirmed the hepatomegaly, splenomegaly, and the undescended testes with hydrocele on the right side. Mutation analysis was carried out for the affected child and his parents. The affected child exhibited a missense mutation in the UROS gene identified as a transversion of A to G at nucleotide 56, resulting in a substitution of tyrosine by cysteine. The patient showed a homozygous mutant profile, and the parents were heterozygous carriers for the mutation. Based on the clinical presentation with onset in early childhood of a photosensitive disorder with erythrodontia, hypertrichosis, fluorescent red urine, absence of porphobilinogen in urine, and a demonstrated mutation of the UROS gene the child was diagnosed as a case of CEP. He was managed with sun avoidance and liberal use of sunscreen administration. He was referred to the surgical center for definitive management of undescended testis. He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens (HLA) matched donor.\"}", "questions": ["What type of transplant is planned for the patient, and what is the relationship of the HLA‑matched donor?"], "ground_truth_arguments": ["He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens ( HLA ) matched donor ."]}
{"id": "CaseReportBench:train-516", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Patient Consent': 'Patient consent was obtained.', 'Case Presentation': 'A 24-year-old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease (CKD) was referred for preconception counseling. Cystinosis was confirmed by an elevated leucocyte cystine level in infancy. Early diagnosis, made possible by cystinosis in an older sibling, and good treatment adherence contributed to delayed kidney disease progression. Electrolyte abnormalities secondary to Fanconi syndrome were treated with daily supplemental dosages of potassium 96 mmol, phosphate 25.2 mmol, and sodium bicarbonate 53.6 mmol. There were no overt extra-renal complications apart from mild photophobia. Her average prepregnancy urine protein-to-creatinine ratio was 132 mg/mmol, α1-microglobulin-to-creatinine ratio was 30.7 mg/mmol, and estimated glomerular filtration rate (eGFR) was 89 ml per minute per 1.73 m 2 . On confirmation of pregnancy, losartan and cysteamine were discontinued. Low-dose aspirin was initiated for the prevention of pre-eclampsia. As expected, proteinuria and eGFR increased during pregnancy. 8 Blood pressure remained normal with no evidence of gestational hypertension or pre-eclampsia. Daily electrolyte supplementation increased to potassium 128 mmol and phosphate 33.6 mmol, with no increase in the dose of sodium bicarbonate. Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein. The pregnancy was complicated by recurrent urinary tract infections (UTIs) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia. After treatment of the complicated UTI, prophylactic oral antibiotics were administered for the remainder of pregnancy without UTI recurrence. She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes. The infant was admitted to the neonatal intensive care unit for 23 days. Cysteamine was reinitiated immediately after delivery and enalapril was initiated at 2 weeks postpartum. The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1-microglobulin-to-creatinine ratio and eGFR were stable ( Figure 1 ). Figure 1 Urinary proteins and eGFR at baseline, during pregnancy and postpartum. eGFR, estimated glomerular filtration rate. While breastfeeding, her delayed-release cysteamine dosage was 675 mg twice daily (0.84 mg/m 2 /d) compared with her prepregnancy dosage of 825 mg twice daily (1.06 mg/m 2 /d). The cysteamine dosage was reduced during breastfeeding as a precaution because of the lack of lactation safety data. She exclusively breastfed for 4 months and discontinued at 5 months. The cysteamine dosage subsequently stabilized at 750 mg twice daily (0.95 mg/m 2 /d). Breastmilk samples were collected and analyzed ( Table 1 and Supplementary Methods ). The calculated relative infant dose was 0.4%. The predicted infant cysteamine dose over 24 hours was 0.52 mg. Infant cysteamine levels were not measured. The infant had normal growth and development at 18 months and a normal leucocyte cystine level. Table 1 Breastmilk cysteamine concentration relative to dose of delayed-release cysteamine bitartrate at steady state Time postdose (h) Breastmilk cysteamine concentration (mg/l) 0 0.12 2 0.76 4 1.87 6 0.51'}", "questions": ["What is the patient’s age, gender, primary renal diagnosis, and CKD stage at the time of referral for preconception counseling?", "What extra‑renal complications, if any, were reported in the patient?", "What were the infant’s growth, developmental status, and leucocyte cystine level at 18 months of age?"], "ground_truth_arguments": ["A 24 - year - old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease ( CKD ) was referred for preconception counseling", "There were no overt extra - renal complications apart from mild photophobia", "The infant had normal growth and development at 18 months and a normal leucocyte cystine level."]}
{"id": "CaseReportBench:train-10", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["What was the condition of the patient's external genitalia as reported in the physical examination?"], "ground_truth_arguments": ["normal female external genitalia with no ambiguity"]}
{"id": "CaseReportBench:train-455", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': 'Our case was a 1-year 5-month-old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath-holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium. The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby’s parents were consanguineous cousins. The father’s thalassemia status could not be elicited. On examination, the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm and the baby was conscious and alert. There was no jaundice or dehydration or abnormal odor. Arterial oxygen saturation (SpO 2 ) was 94%. The capillary refill time was between 3 s and 4 s. The heart rate was 146/min. The respiratory rate was 26/min. Non-invasive blood pressure was 73/44 (54) mm Hg. Respiratory system examination revealed normal chest movements with equal air entry on both sides. Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt. Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs. Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal. The eyes, musculoskeletal system, skin, and cardiovascular systems were normal. The baby was admitted for observation and investigations, and the initial differential diagnosis included alkaptonuria, myoglobinuria, hemoglobinuria, porphyria, and hemochromatosis. He had an under-current viral illness, which was managed symptomatically. The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g/dl (normal 10.5-14 g/dl), packed cell volume, mean corpuscular volume (MCV) and mean corpuscular hemoglobin were low at 31.9% (normal 32-42%), 68 fl (normal 72-88 fl), and 21.8 pg (normal 24-30 pg), respectively. MCV concentration was 32% (normal 31.5-34.5%) and red cell distribution width 17.1% (normal 11-16%). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high-pressure liquid chromatography (HPLC) revealed Hb A0 to be 80.4% and Hb A2 to be 6.1% (normal 2.40-3.60). The HPLC picture on correlation with the complete hemogram suggested β-thalassemia trait. DNA studies confirmed the beta globin gene defect of β-thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ-amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine. No abnormalities were detected on the electroencephalogram, leading us to believe that the breath holding spells were due to anemia. Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict’s reagent, strong alkali (filter paper impregnated with 10% sodium hydroxide turned black within 5 min when dipped into the urine) and ferric chloride (addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color). The urine of an alkaptonuric individual usually appears normal when passed. However, it starts to darken upon standing, and this is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Benedict’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test (with multistix) was negative excluding the role of glucose as reducing substance. For the qualitative assay of HA, to 0.5 ml of sample, a few drops of 10% ammonia was added followed by the addition of 3% silver nitrate solution. A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg/dl (normally HA is not present in urine). Parents’ urine was negative for HA. Due to the financial constraints, confirmatory diagnosis by DNA mutation analysis could not be carried out. The child was treated symptomatically, and he was given vitamin C (50 mg once a day for 3 months), low phenylalanine and tyrosine diet, and advised to monitor counts, get liver and renal function tests carried out every 2 weeks. On the request of his parents, the child was discharged after 3 days and advised to follow-up in the outpatient department (OPD). After 3 months post-therapy, his HA levels had not reduced. Currently, the baby is under follow-up every 6 months in the OPD.'}", "questions": ["What symptoms related to fever, rash, abdominal pain, or constipation were reported in the patient's history?", "What findings were noted on abdominal examination, including organ palpation and the presence or absence of masses?", "What were the results of the liver function tests performed on the patient?"], "ground_truth_arguments": ["no history of fever, rash, abdominal pain, constipation", "Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt", "and liver function were within the reference range."]}
{"id": "CaseReportBench:train-526", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as \"disease causing\" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most \"likely damaging\" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}", "questions": ["What clinical phenotype is expected in individuals who are compound heterozygous for a pathogenic CYP21A2 missense variant and a large CYP21A2 deletion?", "What combination of laboratory findings, clinical presentation, and genetic results is used to confirm a diagnosis of non‑classic congenital adrenal hyperplasia (NC CAH) in affected family members?"], "ground_truth_arguments": ["If p. R124C is pathogenic , the most likely phenotype due to compound heterozygosity for p. R124C and a large deletion would be NC CAH", "a diagnosis of NC CAH was confirmed"]}
{"id": "CaseReportBench:train-205", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case 5': 'A 62-year-old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5-year history of an asymptomatic eruption on the neck. Physical examination revealed numerous soft, oval-to-round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area. Echocardiography was unremarkable. The ophthalmologic examination was normal. Moreover, no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption.', 'Histopathology of cases (1–3)': 'A skin punch biopsy was performed, and the hematoxylin and eosin (H and E) sections revealed a normal-appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.', 'Histopathology of case 4 and 5': 'H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident.', 'Case 3': \"A 68-year-old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years. Physical examination revealed numerous tan to yellowish soft papules over the lateral side of the patient's neck, measuring 2–3 mm. The patient had no systemic symptoms and was otherwise healthy.\", 'Case 4': \"A 61-year-old female patient presented to the clinic with a 2-year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis. On physical examination, there were multiple symmetrically distributed, skin-colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient's neck, upper chest, and the antecubital fossa of both forearms. There was no history of sun exposure or family history of similar cutaneous manifestation.\", 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Case 2': \"A 77-year-old female presented with a 4-year history of gradual appearance of small skin-colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension. However, other systemic examinations were unremarkable, especially for eye, cardiac, or gastrointestinal systems.\", 'Case 1': 'A 71-year-old female presented with a 1–2-year history of asymptomatic skin-colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints. Given the clinical resemblance to PXE, an ophthalmology consult was performed to rule out the presence of angioid streaks. The eye examination was normal.'}", "questions": ["What are the ages of the patients described in each case?"], "ground_truth_arguments": ["62 - year - old", "68 - year - old", "61 - year - old", "77 - year - old", "71 - year - old"]}
{"id": "CaseReportBench:train-600", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': \"A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.\", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}", "questions": ["How were the white blood cell count, platelet count, and hemoglobin level described across the cases?", "Were any cases reported to have a complete blood count within normal limits?", "Which patients were described as having anemia, and how was its severity characterized?", "What spleen findings (e.g., enlargement) were documented for each patient?", "Did any cases show a decrease across all major blood cell types according to the laboratory results?", "What was the serum iron profile result for the patients?"], "ground_truth_arguments": ["mild anemia and splenomegaly", "normal complete blood count", "enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia", "normal serum iron profile", "Total white blood cell count ( 4000 - 11,000 / mm 3 ) 1700 / mm 3 3600 / mm 3 4500 / mm 3 Platelets ( 150,000 - 450,000 / mm 3 ) 107,000 / mm 3 150,000 / mm 3 175,000 / mm 3 Hemoglobin ( female : 12.0 - 15.5 g / dL ) 9.4 g / dL 8.7 g / dL 12 g / dL '"]}
{"id": "CaseReportBench:train-401", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'A 52-year-old man presented at the National Hospital with 5 years history of progressive imbalance of gait, speech and memory impairment, and occasional urinary incontinence. He has never smoked tobacco or taken alcohol. His parents were first cousins from the Hausa ethnic group. His 78-year-old father is alive and well. His 70-year-old mother developed unsteady gait and dysphagia at age 55 years and is now bedridden and blind. His maternal aunt had died of a similar illness at age 39 years. Of his 12 siblings, all four sisters are alive and well, but five of eight brothers died. Three brothers died of unrelated causes, but one died at age 19 years following speech and swallowing difficulties while another one developed frequent falls, dementia, and blindness at age 27 years and died at 45 years. One brother is apparently healthy at age 54 years, but two others aged 42 and 43 years both suffer progressive imbalance of gait. The patient is married to one wife and has had seven children, of whom three have died. One son had frequent falls, seizures, abnormal speech, and blindness at age 8 years and died 3 years later. A daughter died of neonatal sepsis, while another daughter had unsteady gait and speech and swallowing difficulties at 2 years and died at 6 years. On examination, the patient was oriented and scored 28/30 on the Mini-Mental State Examination Scale. He had dysarthria and slow saccades on eye movement. Visual acuity was 6/18 in both eyes, and fundoscopy showed bilateral peripapillary atrophy. He had global hyperreflexia, bilateral ankle clonus, and extensor plantar responses. Muscle power was 5/5 in all limbs. He had a glove-and-stocking sensory loss and bilateral cerebellar signs and scored 16/40 on the Scale for the Assessment and Rating of Ataxia. His mother and 42-year-old brother both had visual impairment, ataxia, and sensory loss on examination. Investigations performed on the patient including a full blood count, serum chemistry, fasting glucose, lipid profile, thyroid function tests, serum Vitamins E and B12 levels, and electrocardiogram were all normal. We suspected a mitochondrial encephalopathy to keep in view SCA7 and von-Hippel–Lindau syndrome. When brain magnetic resonance imaging revealed brainstem atrophy with normal spinal cord, cerebellum, and cerebral hemispheres, we diagnosed SCA7 and tested for CAG repeat expansions at the SCA1, 2, 3, 6, and 7 loci on the proband, his mother and his 42-year-old brother. DNA was extracted from peripheral blood and analyzed by polymerase chain reaction and capillary electrophoresis at the Molecular Diagnostics Laboratory of the National Health Laboratory Service in Cape Town, South Africa. Each of the three samples tested showed expansion mutations of 39 repeats at the SCA7 (ATXN7) gene locus, where one normal allele and one fully expanded allele (10/39) were observed.'}", "questions": ["How was the patient's orientation described, and what type of cognitive assessment was performed?", "What speech and eye‑movement abnormalities (e.g., dysarthria, saccades) were noted?", "What reflex abnormalities, ankle clonus, and plantar responses were observed?", "How was muscle strength characterized across the limbs?", "What sensory deficits and cerebellar findings were observed, and how was ataxia evaluated?", "What did brain magnetic resonance imaging reveal about the brainstem, spinal cord, cerebellum, and cerebral hemispheres?"], "ground_truth_arguments": ["patient was oriented and scored 28/30 on the Mini - Mental State Examination Scale", "dysarthria and slow saccades on eye movement", "global hyperreflexia, bilateral ankle clonus, and extensor plantar responses", "Muscle power was 5/5 in all limbs", "glove - and - stocking sensory loss and bilateral cerebellar signs and scored 16/40 on the Scale for the Assessment and Rating of Ataxia", "brain magnetic resonance imaging revealed brainstem atrophy with normal spinal cord, cerebellum, and cerebral hemispheres,"]}
{"id": "CaseReportBench:train-431", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case report': 'An 11-year-old male had presented to the hospital with a history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4-5 years. There was no history of fever or localized pain. On examination, the blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg (75th-90th centile) and his height measured 138 cm (50th centile). Generalized skin hyperpigmentation was present. Systemic examinations were normal. Local examination revealed bilateral scrotal swelling with normal-appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia (testis length 3.5 cm, penile length 10 cm) and stage 3 for pubic hair. The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size (right and left testicular volume – 2.9 mL and 2.8 mL respectively) with multiple well-defined round to oval hetero-echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B). On screening abdominal sonography, a large well-defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity ( Figs. 3 A and B). Based on these findings, the possibility of testicular malignancy with adrenal metastasis was considered. Contrast-enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands (left>right) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C). Serum tumor markers (alpha-fetoprotein, LDH, and Beta hCG) were negative hence, the diagnosis was reconsidered for the possibility of testicular adrenal rest tumors in an undiagnosed case of congenital adrenal hyperplasia. Fig. 1 (A) Grayscale US of scrotum showing normal-sized right testis with heterogeneous appearance. (B) US image of bilateral testes with multiple nodules containing tiny calcific foci (black arrow). Fig 1 Fig. 2 (A) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. (B) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 (A) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions (white arrow). (B) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions (white arrow). Fig 3 Fig. 4 (A) Contrast enhanced computed tomography (CECT) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia (White arrows). (B) CECT pelvis axial section showing multiple enhancing nodules in the right testis (black arrow). (C) CECT pelvis axial section showing multiple enhancing nodules in left testis (black arrow). Fig 4 X-ray left wrist AP/lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq/L (normal range: 3.5-4.5 mEq/L), whereas the sodium level remained within normal limits at 140 mEq/L. There was a significantly heightened level of 17-hydroxyprogesterone at 1800 ng/dL (normal range: <110 ng/dL), accompanied by normal levels of lactate dehydrogenase (LDH), beta-human chorionic gonadotropin hormone (B-HCG), and alpha-fetoprotein (AFP). Additionally, the serum adrenocorticotropic hormone (ACTH) concentration was elevated, measuring 564 pg/mL (normal range: 7.2-63.3 pg/mL), while cortisol levels were diminished, measuring 5.7 µg/dL (normal range: 7-25 µg/dL). Dehydroepiandrosterone sulfate (DHEA-S) was measured at 5.25 µmol/L (normal range: ≤ 3.726 µmol/L), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng/dL (normal range: 31-65 ng/dL), and there was a reduced level of Inhibin B, measuring 71.1 pg/mL (normal range: 240-445 pg/mL). Collectively, these findings point towards a diagnosis of congenital adrenal hyperplasia. The patient is currently undergoing treatment with hydrocortisone and is on regular follow-up. The 3-month follow-up revealed clinical improvement with a reduction in testis size and decreased ACTH levels, indicating positive progress. Fig. 5 X-ray of left wrist AP and a lateral view showing accelerated bone age corresponding to approximately 18 years. Fig 5', 'Patient consent': 'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.'}", "questions": ["What skin abnormalities or pigmentation changes were noted on physical examination of the patient?"], "ground_truth_arguments": ["Generalized skin hyperpigmentation was present"]}
{"id": "CaseReportBench:train-117", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What hypertension diagnosis was reported for the patient, including the age of onset and any associated treatment?"], "ground_truth_arguments": ["hypertension"]}
{"id": "CaseReportBench:train-9", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case 2': 'This patient too showed considerable hyperkeratosis of palms and soles. Intraoral examination showed more teeth present. Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds. All teeth had deep periodontal pockets and grade II mobility. Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits. On the basis of history, clinical and radiographical features a diagnosis of Papillon-Lefevre syndrome was made.', 'CASE REPORT': 'An 18-year-old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi-Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16-year-old brother also complained of similar problems. Systemic history-both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2-3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.', 'Case 1': 'Patient showed bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees. Intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility. Orthopantomograph showed severe horizontal bone loss..'}", "questions": ["What genetic disorder is associated with early‑onset palmoplantar hyperkeratosis and severe periodontitis?"], "ground_truth_arguments": ["Papillon - Lefevre syndrome"]}
{"id": "CaseReportBench:train-301", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Chief complaints': 'A 33-year-old woman was admitted to the psychiatric acute ward with the following symptoms: delusions of persecution, auditory hallucination, impulsive behavior, and emotional instability.', 'Personal and family history': 'There was no family history of psychiatric diseases.', 'CASE SUMMARY': 'A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported. The patient presented with cholestasis, cataract, Achilles tendon xanthoma, and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood. After the characteristic CTX findings on imaging were obtained, a pathological examination of the Achilles tendon xanthoma was refined. Re-placement therapy was then initiated after the diagnosis was clarified by genetic analysis. During hospitalization in the psychiatric ward, the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis. After the patient’s history of CTX was identified, the patient was diagnosed with organic schizophrenia-like disorder, and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication.', 'Physical examination': 'During hospitalization in the psychiatric ward, the patient’s brief psychiatric rating sale (BPRS) score was 40, her Wechsler intelligence scale score was 65, and the total biliary acid returned to normal levels. Nervous system examination showed normal muscle tone in the extremities, grade 5 muscle strength, instability in the heel-knee-tibia test of the right lower extremity, and a positive Romberg sign. In the mental status examination, the patient exhibited the following: verbal auditory hallucination; delusions of persecution; negative perceptions; irritability; childish emotions; poor general knowledge, understanding, judgment, and calculation; impulsivity; and lack of insight.', 'Imaging examinations': 'Brain magnetic resonance imaging (MRI) revealed symmetrical patchy abnormal signals in the dentate nuclei and deep medulla of the bilateral cerebellar hemispheres. These signals exhibited a slight decrease in signal intensity on T1-weighted images (T1WI) (Figure 2A ) and a slight increase in signal intensity on fluid attenuated inversion recovery (FLAIR) (Figure 2B ). Left-ankle-joint MRI showed that the inhomogeneous area had a considerable local thickening of the left Achilles tendon. The area displayed clear boundaries measuring approximately 6.6 cm × 1.2 cm and exhibited a slightly elevated signal intensity on T1WI and a similar slightly elevated signal intensity on the proton density weighted image, accompanied by linear hypointensity within (Figure 1B ). Brain magnetic resonance spectroscopy (MRS) showed decreases in N-acetylaspartate (NAA) intensities and increases in lactate and lipid signals (Figure 2C and D ).', 'Laboratory examinations': 'After nearly 3 years of adequate chenodeoxycholic acid treatment, the total biliary acid level returned to normal.', 'History of present illness': \"For 6 mo, the patient showed hostility towards her colleagues, firmly believing that they wanted to harm her. She could hear abusive voices of colleagues when she was alone. The false belief and voice interfered with the social relations and behavior of the patient, leading to outrunning behavior. In addition, the patient exhibited impulsive acts and temperamental behavior, such as tearing people's clothes, smashing things, standing outside naked when she became excited, and running around at midnight. She also experienced severe depression for several days, with crying and expressing a desire to commit suicide by euthanasia.\", 'History of past illness': 'According to her mother, the patient has been weak and obtuse since childhood and was unable to pass primary school exams. She required supervision and care from her family in her personal life. Despite being able to work, she could not perform her job well and did not get along with her colleagues, leading to her dismissal from several companies. At age 18, she underwent cataract surgery, and at age 26, she underwent cholecystectomy for cholestasis. A review of the patient’s medical records revealed that she presented with swelling in her left Achilles tendon, pain, and skewed walking to the right side 5 years ago. Three years ago, she was admitted to the neurology department, where biochemical tests revealed an elevated total biliary acid level of 11.2 µmol/L (normal value ≤ 10.0) and decreased levels of chenodeoxycholic acid and ursodeoxycholic acid. Subsequently, a biopsy of the left Achilles tendon was performed, revealing numerous lipid crystals and a few foamy macrophages (Figure 1A ). The patient underwent genetic analysis, which identified two mutations in the CYP27A1 gene associated with CTX: c.1263 + 3G>C and c.379C>T. On the basis of these findings, the patient was ultimately diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/d) and rosuvastatin (10 mg/d).'}", "questions": ["What is the patient's age at presentation?"], "ground_truth_arguments": ["33 - year - old", "33 - year - old"]}
{"id": "CaseReportBench:train-567", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case Report': 'We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumor was made; biopsy was deferred and hormonal treatment was modified. A 9-year-old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour. The cortisol level was low, and levels of 17 alpha-hydroxyprogesterone, plasma corticotrophin (ACTH), and testosterone were high. Scrotal ultrasound revealed well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses with posterior acoustic shadowing in both testes, in the medial aspects near the mediastinum testis. The right testicular mass measured 1.3×1.1 cm, and the left testicular mass measured 1.5×1.2cm ( Figures 1, 2 ). On colour Doppler, the masses had minimal internal vascularity ( Figure 3 ). The rest of the testes showed normal flow. The epididymis and cord structures were normal. There was no evidence of hydrocoele on both sides. Testicular tumor markers were negative. Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement ( Figure 4 ). In a patient with CAH and bilateral testicular masses that had a typical sonographic appearance, a diagnosis of testicular adrenal rest tumor was made, and biopsy was deferred. Hormonal treatment was intensified, and the testicular masses are followed up. The patient improved clinically, which was associated with a decrease in testosterone and 17 alpha-hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months. Currently, the patient is advised to undergo follow-up ultrasound examinations every 3 months.'}", "questions": ["What signs of early sexual development and growth abnormalities were described in the patient?", "What specific diagnosis was assigned to the bilateral testicular masses in this patient?", "What acute endocrine event occurred when the patient was one year old leading to the CAH diagnosis?", "Which endocrine laboratory results were abnormal at the time of presentation?", "What findings did the abdominal ultrasound show concerning the suprarenal (adrenal) region?", "How were the bilateral testicular masses characterized on scrotal ultrasound?", "How did intensified hormonal therapy influence hormone levels and the size of the testicular masses on follow‑up imaging?", "What evidence of precocious puberty is reported in the case?"], "ground_truth_arguments": ["precocious puberty", "testicular adrenal rest tumor", "adrenal crisis", "precocious puberty, short stature", "The cortisol level was low, and levels of 17 alpha - hydroxyprogesterone, plasma corticotrophin ( ACTH ), and testosterone were high", "Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement", "bilateral testicular masses that had a typical sonographic appearance", "testicular adrenal rest tumor", "decrease in testosterone and 17 alpha - hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months"]}
{"id": "CaseReportBench:train-119", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["At what age did each patient first notice symptoms related to CTX?", "Which developmental periods (e.g., infancy, childhood) are referenced as the time of initial symptom onset?"], "ground_truth_arguments": ["early age", "childhood", "infancy"]}
{"id": "CaseReportBench:train-110", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A 52-year-old man presented at the National Hospital with 5 years history of progressive imbalance of gait, speech and memory impairment, and occasional urinary incontinence. He has never smoked tobacco or taken alcohol. His parents were first cousins from the Hausa ethnic group. His 78-year-old father is alive and well. His 70-year-old mother developed unsteady gait and dysphagia at age 55 years and is now bedridden and blind. His maternal aunt had died of a similar illness at age 39 years. Of his 12 siblings, all four sisters are alive and well, but five of eight brothers died. Three brothers died of unrelated causes, but one died at age 19 years following speech and swallowing difficulties while another one developed frequent falls, dementia, and blindness at age 27 years and died at 45 years. One brother is apparently healthy at age 54 years, but two others aged 42 and 43 years both suffer progressive imbalance of gait. The patient is married to one wife and has had seven children, of whom three have died. One son had frequent falls, seizures, abnormal speech, and blindness at age 8 years and died 3 years later. A daughter died of neonatal sepsis, while another daughter had unsteady gait and speech and swallowing difficulties at 2 years and died at 6 years. On examination, the patient was oriented and scored 28/30 on the Mini-Mental State Examination Scale. He had dysarthria and slow saccades on eye movement. Visual acuity was 6/18 in both eyes, and fundoscopy showed bilateral peripapillary atrophy. He had global hyperreflexia, bilateral ankle clonus, and extensor plantar responses. Muscle power was 5/5 in all limbs. He had a glove-and-stocking sensory loss and bilateral cerebellar signs and scored 16/40 on the Scale for the Assessment and Rating of Ataxia. His mother and 42-year-old brother both had visual impairment, ataxia, and sensory loss on examination. Investigations performed on the patient including a full blood count, serum chemistry, fasting glucose, lipid profile, thyroid function tests, serum Vitamins E and B12 levels, and electrocardiogram were all normal. We suspected a mitochondrial encephalopathy to keep in view SCA7 and von-Hippel–Lindau syndrome. When brain magnetic resonance imaging revealed brainstem atrophy with normal spinal cord, cerebellum, and cerebral hemispheres, we diagnosed SCA7 and tested for CAG repeat expansions at the SCA1, 2, 3, 6, and 7 loci on the proband, his mother and his 42-year-old brother. DNA was extracted from peripheral blood and analyzed by polymerase chain reaction and capillary electrophoresis at the Molecular Diagnostics Laboratory of the National Health Laboratory Service in Cape Town, South Africa. Each of the three samples tested showed expansion mutations of 39 repeats at the SCA7 (ATXN7) gene locus, where one normal allele and one fully expanded allele (10/39) were observed.'}", "questions": ["Describe the patient's ocular findings, including eye movement characteristics, visual acuity, and fundoscopic observations."], "ground_truth_arguments": ["and slow saccades on eye movement. Visual acuity was 6/18 in both eyes, and fundoscopy showed bilateral peripapillary atrophy"]}
{"id": "CaseReportBench:train-151", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}", "questions": ["At what age were the twins diagnosed with nephropathic cystinosis, and what type of genetic alteration in the CTNS gene was identified?"], "ground_truth_arguments": ["diagnosed in infancy with NC and found to have a 57 - kb deletion of the CTNS gene , the most frequent cause of NC in Western populations ."]}
{"id": "CaseReportBench:train-360", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["What ocular motor abnormalities are reported, and at what point in the disease course did they first become evident?", "Which cervical or axial muscle abnormalities are described, and what is known about their onset timing?", "Describe the distribution and severity of limb muscle weakness, indicating proximal versus distal involvement, strength grades, and any related findings such as winging scapula or generalized wasting (do not include tendon reflex information).", "What electromyography (EMG) or needle‑EMG findings are reported for specific muscles, and what type of alterations (neurogenic, myopathic, abnormal spontaneous activity) were observed?", "Summarize the respiratory dysfunction, including presence of hypercapnia, oxygenation status, diaphragm movement, need for intubation, mechanical ventilation, tracheostomy, and any recurrence of insufficiency.", "What functional limitations related to trunk control and sitting are documented, including ability to sit with support versus unsupported?", "How is mitochondrial myopathy characterized in terms of the muscle groups it affects (extra‑ocular, axial, shoulder‑girdle, respiratory)?"], "ground_truth_arguments": ["bilateral ptosis since age 23y,", "anterocollis since at least age 40y.", "bilateral proximal weakness of the upper limbs, a winging scapula bilaterally", "Needle-(electromyography ) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations", "mild weakness of the lower limbs ( M5-/M4 + )", "needle - EMG of the rectus abdominis muscle revealed abnormal spontaneous activity", "acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "hypercapnia due to muscular respiratory insufficiency.", "ptosis, ophthalmoparesis, weak head anteflexion and retroflexion ( M5- ), weakness of the upper limbs with distal predominance ( M4 to M5- ), proximal weakness of the lower limbs ( M5- )", "generalized wasting,", "The diaphragm was moving normally.", "respiratory insufficiency with hypercapnia recurred", "he was able to sit with support during daytime", "Unsupported sitting was impossible due to affected truncal muscles.", "muscular respiratory insufficiency.", "ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y.", "mitochondrial myopathy affecting not only the extra - ocular and the axial muscles but also the shoulder girdle and respiratory muscles", "muscular respiratory insufficiency"]}
{"id": "CaseReportBench:train-139", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 12-year-old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days. On physical examination the child was found to have retarded growth (dwarfism) and a pendulous abdomen. Per abdominal examination revealed hepatomegaly. USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm–sized, well-defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well-circumscribed, low-attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted. Hepatomegaly with diffusely low attenuation of liver, bilateral renal calculi (which hinted at hyperuricemia – a known feature of von Gierke disease), clinical features of dwarfism, facial dysmorphism, and protuberant abdomen, were all features that favored the diagnosis of von Gierke disease. Moreover, in the pediatric age-group, liver tumors are rare and hepatic adenoma occurs almost exclusively in patients with underlying von Gierke disease. CT scan features like well-circumscribed margins, subcapsular location, and contrast enhancement also supported the diagnosis of hepatic adenoma. Based on these CT scan findings and clinical features, a probable diagnosis of hepatic adenoma in a case of type Ia glycogen storage disease (von Gierke disease) was suggested. Preoperative laboratory evaluation revealed increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits. The patient was operated and the mass in the liver was surgically resected. The specimen was sent for histopathological examination along with a small bit of liver tissue, which showed PAS-positive glycogen-rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma.'}", "questions": ["Provide the patient's demographic details, who accompanied them to the hospital, and a general description of their abdominal symptoms, including duration and location."], "ground_truth_arguments": ["A 12 - year - old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days"]}
{"id": "CaseReportBench:train-87", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine. She was born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively. As a 3-week-old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed. At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day. Physical examination revealed multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back. The spleen was of normal size and physical and intellectual development was normal. Again, moderate hemolytic anemia was also found (red blood cells: 3.68 × 10 6, hemoglobin: 10.6 g/dl, hematocrit: 33.0%, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G/DL, platelets 124 × 10 3 ml, white blood cells: 3.6 × 10 3, reticulocytes: 58 (5-15)), but did not require a blood transfusion. Further laboratory investigations were as follows: urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal. Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable. Now, aged 14 years, the severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands. Using all available measures to protect herself from the sun (hat, eyeglasses, cosmetic camouflage, and long sleeves) has not succeeded in protecting her from the mutilating effects of sun. This has caused scarring of her skin at sun-exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp. In addition, she has restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust. Moderate hypertrichosis on the back of the neck was also noted and her teeth have progressively stained brownish-red. The results of the biochemical investigations are summarized in Table 1 . Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High-pressure liquid chromatography of the urine demonstrated 85% of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617. These results confirmed a diagnosis of CEP. Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T>C (p.Cys73Arg) in exon 4 and c.683c>T (p.Thr228Met) in exon 10. These missense mutations have previously been described, where the patient had a moderate to severe phenotype.'}", "questions": ["Describe the photosensitive skin manifestations, including the pattern of blistering and scarring, and list all body sites where they occur.", "Identify all areas where hypertrichosis is present and describe its severity.", "What deformities and functional limitations have resulted from the chronic photosensitive skin damage, especially affecting the face and hands?", "Detail any hair loss observed, specifying the affected regions and their relationship to sun exposure.", "What ocular symptoms does the patient experience, and how are they linked to eyelash loss or other skin changes?"], "ground_truth_arguments": ["easy skin blistering and scarring", "multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back", "severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands.", "scarring of her skin at sun - exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp", "restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust", "Moderate hypertrichosis on the back of the neck was also noted"]}
{"id": "CaseReportBench:train-160", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["For each patient, state the age at which PXE was diagnosed and the age at the most recent clinical event reported in the document (provide only one most‑recent age per patient).", "For each patient, summarize the reported claudication description, including any severity adjectives and any maximal walking distance that is mentioned.", "For each patient, list all ankle‑brachial index (ABI) values that are explicitly reported, specifying the limb (right or left) and the numeric value; do not mention limbs for which no ABI is given.", "For each patient, describe every reported superficial femoral artery (SFA) lesion, indicating the side, the degree of stenosis (e.g., >70%, subtotal), and any notable features such as calcification or lesion length.", "For each patient, enumerate every endovascular SFA intervention that was actually performed, providing the procedure type, device/model if mentioned, side treated, and its chronological order relative to earlier procedures. Exclude any mention of imaging findings or thrombosis unless a therapeutic action is described.", "For each patient, list any femoral‑popliteal saphenous bypass surgeries that were performed, specifying the limb treated and whether the bypass was done after a failed endovascular attempt. Include only surgeries explicitly described as performed.", "For each patient, detail repeat therapeutic actions that were undertaken because of a documented failure (restenosis, thrombosis, or occlusion) of a prior procedure, stating the prior failure and the subsequent treatment. Include only actions that are explicitly reported as performed."], "ground_truth_arguments": ["Patient 1 ( a woman, 68 years old ) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle - brachial pressure index ( ABI ) at rest of 0.69 on the right and 0.85 on the left", "Patient 2 ( a woman, 65 years old ) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg ( < 150 m ) with an ABI of 0.51 and 0.68 on the right.", "Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting ( S.M.A.R.T. stent; Cordis, Bridgewater, NJ ) for stenosis of the right SFA", "One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral - popliteal saphenous bypass", "angioplasty of the SFA was performed", "again treated by angioplasty", "Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs"]}
{"id": "CaseReportBench:train-430", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'Case 2': \"Four days after the development of fever, cough, and rhinorrhea, a 6-month-old, previously healthy girl was admitted with generalized tonic-clonic seizure and mental change, as well as increased rigidity of the extremities. CT images of the brain, obtained at another hospital, depicted symmetric low-density lesions in the thalami and external capsules. Two months earlier, the patient's elder sister had died of acute encephalopathy. Conventional brain MR imaging performed on the second day of hospitalization indicated that symmetric T1- and T2-prolonged areas were present in the thalami and external capsules. T2*-weighted gradient-echo images clearly showed that within the thalamic lesions, acute hemorrhage had occurred. After the intravenous administration of gadolinium-diethylene triamine penta-acetic acid, the lesions showed no abnormal enhancement and ADC mapping revealed areas of low signal intensity within them ( Fig. 2A ). Localized proton MR spectroscopy using a stimulated echo-acquisition mode sequence (TR/TE=3000/30, 96 acquisitions, volume of interest=7 mL) showed a small doublet at 1.33 ppm ( Fig. 2B ). Laboratory findings indicated slightly increased levels of serum aspartate aminotransferase, lactate, and ammonia, though the lactate level rapidly returned to normal. CSF analysis revealed increased protein content without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for DNA of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA. The patient was thought to be suffering from acute necrotizing encephalopathy, and was treated with mannitol, acyclovir, and steroid. Her mental state improved and on the second day of hospitalization her level of alertness was almost normal. The extremities gradually became less rigid, and follow-up brain MR imaging and MR spectroscopy performed one week later revealed marked improvement of the initial lesions and disappearance of the doublet at 1.33 ppm ( Fig. 2C ).\", 'Case 1': 'Two days after the onset of fever, vomiting, and diarrhea, a 10-month-old previously healthy boy was admitted with generalized tonic-clonic seizure. Brain CT, performed elsewhere, revealed the presence of symmetric low-density thalamic lesions. On admission, he was drowsy and showed decerebrate rigidity, without focal neurologic signs. Conventional brain MR images obtained using a 1.5-T system on the second day of hospitalization depicted symmetric distribution of T1- and T2-prolonged areas in the thalami ( Fig. 1A ), tegmentum of the pons, and periventricular white matter. T2*-weighted gradient-echo images (TR/TE = 800/30, flip angle = 20°) demonstrated low signal intensities within the thalamic lesions, suggesting acute hemorrhage ( Fig. 1B ). After the intravenous administration of gadolinium-diethylene triamine penta-acetic acid, the lesions showed no abnormal enhancement. Diffusion-weighted MR imaging (b value=1000 sec/mm 2 ) demonstrated high signal intensity in all the lesions, though this was absent in the central portion of thalamic lesions, and other than in this same area, apparent diffusion coefficient (ADC) mapping revealed low signal intensity ( Fig. 1C ). Localized proton MR spectroscopy of the thalami using a stimulated echo-acquisition mode sequence (TR/TE=3000/30, 96 acquisitions, volume of interest=7 mL) showed that compared with an age-matched control subject, peak intensities were higher, occurring at 2.0-2.5 and 0.8-1.5 ppm ( Figs. 1D, E ). Laboratory findings on admission showed increased serum aspartate and alanine aminotransferase levels, though those of blood ammonium and lactate were normal. Cerebrospinal fluid (CSF) analysis showed slightly increased protein content, without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for deoxynucleic acid (DNA) of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA, which would indicate mitochondrial encephalopathy with lactic acidosis and stroke-like episode (MELAS) syndrome. The patient was treated with acyclovir, an antiviral agent, and steroid. His mental state improved, and on the fourth day of hospitalization he was almost alert. Cognitive functions gradually improved, though severe motor deficits remained. Follow-up brain MR imaging performed three months later revealed residual atrophic change in the previously observed lesions; both T1- and T2-weighted images depicted small areas of high signal intensity at the center of the thalami, indicating residual subacute hemorrhage.'}", "questions": ["How are the respiratory symptoms described in the case?"], "ground_truth_arguments": ["cough, and rhinorrhea,"]}
{"id": "CaseReportBench:train-374", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}", "questions": ["What were the patient's demographic and genetic characteristics, and what clinical presentation led to the initial hospital admission?", "What age range or developmental stage was the patient in when the bilateral gonadectomy was performed?"], "ground_truth_arguments": ["A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency", "At 2 years and 5 months, she underwent bilateral gonadectomy"]}
{"id": "CaseReportBench:train-25", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Microbial defects': 'In PLS, neutrophil function test showed reduced response to staphylococcus spp. and Actinobacillus actinomycetemcomitans . There is a hypothesis that herpes viruses together with pathogenic bacteria, including A. actinomycetemcomitans and underlying host defense disorders, participate in the development of PLS periodontitis. Presence of numerous virulence factors such as leukotoxin, collagenase, endotoxin, epitheliotoxins and fibroblast-inhibiting factor, suggests that PLS is mediated bacteriologically and therefore could be treated to some improvement with antibiotics. The serum of the patients showed high immunoglobulin G (IgG) titer against A. actinomycetemcomitans . Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples. Antibiotic therapy was associated with elimination of A. actinomycetemcomitans from the periodontal pockets and serum IgG titers against A. actinomycetemcomitans decreased in the patients.', 'Clinical examination': 'Extra-oral examination On extra-oral examination, patient presented with well-demarcated, yellowish, keratotic plaques over the skin of palms and soles extending on to the dorsal surfaces. Skin of both palms and soles was peeling off leaving underlying red shiny area suggestive of keratoderma. Well circumscribed, psoriasiform, erythematous, scaly plaques were also present on the elbows and knees bilaterally along with dystrophy and transverse grooving of the nails. The fingers were pointed giving clawed appearance. Intra-oral examination Intra-oral examination revealed edentulous area between teeth 44 and 33 and 11, 21 and 22 were also missing. Edentulous maxillary and mandibular ridges were covered with normal mucosa. The teeth present were 12, 13,14,15,16,22, 24, 25, 26, 33, 34, 35, 36, 44, 45 and 46 covered with soft deposits and band of subgingival calculus. Gingiva was fiery red in color with inflammatory gingival enlargement Iva Ingle Classification grade II. Pathological migration was associated with 12, 14, 23, 24, 33 and 34. On assessment grade III mobility was present in relation with 14, grade II in relation with 24, 25, 33, 34, 36 and 44. Remaining teeth were present with grade I mobility. There was the presence of recession grade III in relation with 14 and 33. Extra-oral examination She complained about dry scaly skin of palms and soles like her sister, but she has not taken any dermatological treatment for that. On examination, well-demarcated keratotic plaques over the skin of her palms and soles, extending on to dorsal surfaces were present. Intra-oral examination She showed the presence of 16, 26, 31, 36, 46, 41 and 53 in the oral cavity. There is grade III recession and grade II mobility in 53. Remaining teeth revealed the presence of soft deposits and grade I mobility.', 'Case 2': 'Second patient was a 6-year-old sister of the above patient. She was asymptomatic before 2 years. Her father noticed mobility in relation with some of her deciduous teeth and then early exfoliation of same. Her elder sister had same complain, so he brought her also for a checkup and treatment at Government Dental College and Hospital, Ahmadabad.', 'Radiographic findings': 'Orthopantogram showed extensive alveolar bone loss in all remaining teeth. The alveolar bone around the mobile teeth was devoid of definable lamina dura. An extensive alveolar bone loss was noted, giving the teeth 31, 41 and 43 a “floating in air appearance,” which were extracted afterwards. Radiographically, right and left lateral oblique radiographs show angular bone loss and periodontal widening present in relation with 36 and 46. There are developing tooth germs of permanent tooth are also seen.', 'Immunological defects': 'CTSC is involved in a wide variety of immune and inflammatory responses. It plays an essential role in activating serine proteinases expressed in the granules of bone marrow derived cells from both the myeloid and lymphoid series. The serine proteinases are implicated in a variety of inflammatory and immune processes, including phagocytic destruction of bacteria and activation of phagocytic cells and T-lymphocytes. Therefore, deficiency of CTSC function will result in loss of immunological response, leading to liability of infection. Recently, impairment of natural killer (NK) cell cytotoxic function is the first consistent immune dysfunction reported in PLS. This suggests that the impaired NK cell cytotoxicity might contribute to the pathogenesis of PLS associated periodontitis. A defect that principally interferes in phagocytic function is likely to give rise to aggressive periodontitis of PLS since nearly identical features occur in other defects of phagocytic function. The loss of CTSC function and subsequent inactivity of neutrophil serine proteinases may cause deregulation of localized polymorphonuclears response in inflamed periodontal tissues, leading to the severe tissue destruction in PLS.', 'Case 1': 'A 14-year-old girl, visited to outpatient Department of Periodontia, Government Dental College and Hospital, Ahmedabad, India with chief complain of premature loss of deciduous and permanent teeth and mobility in remaining teeth. She was the first child born to apparently healthy non-consanguineous parents. History revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4-5 years. Similarly, her permanent teeth were lost prematurely after erupting normally. Patient was having complained of mobility and bleeding gum before 2 years, visited a periodontist and undergone treatment in the form of periodontal flap surgery. After one and half year, patient was having same complain and came to Government Dental College and Hospital, Ahmedabad. There was no family history of ichthyosis or hereditary or acquired palmoplanter keratodermas. The patient also gave a history of development of fissures, thickening and flaking in the skin of palms and soles that resulted in peeling off of skin leaving red thin area underneath since age of 3-4 years. She had exacerbation and remissions of the skin lesions since early childhood, visiting dermatologist regularly, but no improvement was seen. She repeatedly contracted systemic infections.'}", "questions": ["How did the patients' serum IgG levels change over the course of treatment?", "What microbiological findings were reported from periodontal pocket samples, and how did they evolve with therapy?", "What radiographic abnormalities of the alveolar bone and surrounding structures were reported on the orthopantogram?"], "ground_truth_arguments": ["serum of the patients showed high immunoglobulin G ( IgG ) titer against A. actinomycetemcomitans. Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples", "serum IgG titers against A. actinomycetemcomitans decreased in the patients", "Orthopantogram showed extensive alveolar bone loss in all remaining teeth. The alveolar bone around the mobile teeth was devoid of definable lamina dura. An extensive alveolar bone loss was noted, giving the teeth 31, 41 and 43 a “ floating in air appearance, ” which were extracted afterwards. Radiographically, right and left lateral oblique radiographs show angular bone loss and periodontal widening present in relation with 36 and 46. There are developing tooth germs of permanent tooth are also seen."]}
{"id": "CaseReportBench:train-192", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 4-year-old female patient with a nasal anomaly was admitted to our outpatient clinic. She was born 2300 g prematurely on her 37 th gestational week from a 34-year-old mother with a history of five pregnancies, two still births and two abortions. On her physical examination, she had a left-sided supernumerary nostril and cliteromegaly. Her laboratory studies revealed low levels of androstenedione and her history showed that she had medical therapy for 1 year for her congenital adrenal hyperplasia. No additional anomaly except patent foramen ovale was detected in her work-ups. Paranasal sinus computed tomography study revealed that her left-sided accessory nostril opened to the left nasal cavity. The patient was operated, the opening of the supernumerary nostril to the nasal cavity was obliterated and the widened nostril was narrowed by excisions from the alar ground and lateral side. A revision toward the nostril asymmetry is planned 1 year after the operation.'}", "questions": ["What were the laboratory findings regarding the patient's androstenedione levels?", "What did the paranasal sinus computed tomography show about the left-sided accessory nostril's relationship to the nasal cavity?"], "ground_truth_arguments": ["low levels of androstenedione", "Paranasal sinus computed tomography study revealed that her left - sided accessory nostril opened to the left nasal cavity"]}
{"id": "CaseReportBench:train-136", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': 'A 2-year-old boy was referred to our hospital due to developmental delay, ichthyosis, asthma, and recurrent pneumonia. His parents were related but there was no history of asthma, and allergic disorders in his family, and close relatives. He had ichthyosis at birth, and mild intermittent asthma, and 2 episodes of pneumonia also were observed in his first year of life. He had no history of seizure. His physical examination revealed spastic diplegia and brisk deep tendon reflexes in lower limbs. He was not able to stand or walk, independently and his speech was limited to 2–3 meaningful words. Acquisition of other developmental skills was mildly delayed with achieving head control and sitting without support at 5 and 12 months, respectively. Extensive hyperkeratosis and scaling of the skin were seen particularly in the dorsum of hands, skin flexures, and lower abdomen ( Fig. 1 ). Funduscopic examination was normal. Electroencephalography, routine laboratory tests, and chromosomal study were also normal. Magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the deep white matter around the trigons of lateral ventricles ( Fig. 2 ). Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging and parakeratosis consistent with ichthyosis. Molecular genetics study utilizing sequencing of the polymerase chain reaction product using the exon-specific primers revealed a c.370-372 (GGA) deletion mutation in the second exon of ALDH3A2 gene in a homozygote state. Therefore, the diagnosis of SLS was confirmed. The patient was treated, symptomatically with inhaled corticosteroid, and bronchodilator, local paraffin applicants, and rehabilitation therapy.'}", "questions": ["What are the patient’s basic demographic characteristics (e.g., age group, sex) and is there any known parental consanguinity?", "Which clinical problems prompted the patient’s referral to the hospital?", "What is the family history concerning asthma and other allergic disorders?", "When was the dermatologic abnormality first identified, and how would you characterize the patient's asthma?", "What is the pattern of pneumonia occurrence in the first year of life?", "What does the patient’s medical history reveal about seizures?"], "ground_truth_arguments": ["A 2 - year - old boy was referred to our hospital due to developmental delay, ichthyosis, asthma, and recurrent pneumonia. His parents were related but there was no history of asthma, and allergic disorders in his family, and close relatives. He had ichthyosis at birth, and mild intermittent asthma, and 2 episodes of pneumonia also were observed in his first year of life. He had no history of seizure"]}
{"id": "CaseReportBench:train-322", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Diagnoses:': 'The proband underwent a thorough examination in our hospital and was diagnosed as mitochondrial encephalomyopathy. The proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene. Although his parents did not carry the mutation.', 'Case presentation': \"The proband was a 12-year-old boy on first visiting to our hospital. The proband was the first and the only child of his healthy, nonconsanguineous parents of Han Chinese descentand was born at 38 weeks gestation by spontaneous delivery. The proband had no postnatal adaptation, and the Apgar score was unknown. He was admitted to the hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after the treatment of unexplained fever and somnolence. The highest temperature was 37.8°C, accompanied by vomiting 4 to 5 times on the same day, with insufficient spirits. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of our hospital (no. 2018021). Informed written consent was obtained from all participants prior to their enrollment in this study. The proband underwent a thorough examination in our hospital, including electroencephalogram, echocardiogram, electrocardiogram, brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), physical examination, laboratory examination, and mitochondrial gene detection. Genomic DNA from the family was extracted from peripheral whole blood samples using the genomic DNA extraction kit (Qiagen) according to the manufacturer's instructions. The entire mitochondrial genomes of the family were PCR amplified in 24 overlapping fragments by using sets of the light strand and the heavy strand oligonucleotide primers, as described elsewhere. Each fragment was purified and subsequently Sanger sequencings were conducted by TSINGKE Biological Technology(Beijing, China). The resultant sequence data were compared with the revised consensus Cambridge sequence (GenBank accession no. NC-012920). His electroencephalogram showed clear increase of 4–5c/s theta waves, 2–3c/s delta waves, with a small amount of sharp waves. His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right (Fig. 1 A). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS (Fig. 1 B). Normal structure and ejection fraction were observed via echocardiography. Serum lactate dehydrogenase, creatine kinase, α-hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range. Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation (Fig. 2 ). The patient was treated according to the diagnosis of mitochondrial encephalomyopathy. Intravenous acyclovir, ceftriaxone and dexamethasone were used for antiviral, antimicrobial, and anti-inflammatory therapy, respectively. Intravenous mannitol was gradually tapered for reducing intracranial pressure with furosemide for inducing diuresis. Intravenous arginine could help to treat alkalosis and supple some essential amino acids. Oral oxiracetam capsules, vitamin B1, and coenzyme Q10 were used for providing nutrition and improving energy. His medications were 30 mg vitamin B1, 0.1gm vitamin C and mecobalamin 750 μg daily after discharge from our hospital. The patient was able to walk and talk slowly with improved writing skills and no stroke-like episodes. The neurological examination was negative and muscle tension was identified as grade V.\", 'Patient concerns:': \"A 12-year-old boy was admitted to Shaoxing People's Hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after treatment of unexplained fever and somnolence.\"}", "questions": ["Did mitochondrial sequencing reveal a pathogenic mutation in the proband, and was the same mutation present in his parents?", "What abnormalities were observed on the proband's brain MRI, and what metabolic abnormalities were reported on proton MRS of the same region?", "What did the echocardiographic examination reveal about the proband's cardiac structure and ejection fraction?", "What were the main abnormalities reported in the proband's serum laboratory tests and cerebrospinal fluid analysis?"], "ground_truth_arguments": ["proband carried the pathogenic heteroplasmic mutation A3243 G mutation in mitochondrial 12S rRNA gene", "His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right ( Fig. 1 A ). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS", "Normal structure and ejection fraction were observed via echocardiography", "Serum lactate dehydrogenase, creatine kinase, α - hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range", "Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243 G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation"]}
{"id": "CaseReportBench:train-325", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Presentation': \"We present a case of cardiac paraganglioma with left coronary artery involvement. The patient was a 22-year-old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension. Results of transthoracic echocardiography and renal Doppler imaging were normal, and plasma and urine metanephrine levels were within normal limits. Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation. New transthoracic echocardiography showed high velocities in the pulmonary artery and a mass with intermediate echogenicity located at the base of the heart in close relation to the aorta and the pulmonary artery, extending into the left atrioventricular groove ( Figure 1, Videos 1 and 2 ). Free metanephrines in plasma (noradrenaline 4,886.67 pg/mL) and urine (noradrenaline 1,426.9 μg/24 h) were high. Figure 1 Transthoracic echocardiography. Shown is a mass ( white arrow ) with intermediate echogenicity in relation to the great vessels. To obtain better characterization, cardiac magnetic resonance was performed and showed a middle mediastinal mass located in the left atrioventricular groove, extending posteriorly to the left atrial roof and almost surrounding the pulmonary artery anteriorly. The mass was closely associated with the aortic root, but the emergence and path of the left coronary artery and its branches were not adequately visualized ( Figure 2 ). Tissue characterization sequences showed a mass with a heterogeneous appearance on T2-weighted sequences and slightly hyperintense on T1-weighted and T2 with fat saturation sequences ( Figure 2 ). Important mass vascularization was demonstrated with the perfusion sequence, which showed rapid uptake of contrast shortly after its administration. We also found focal late gadolinium enhancement at the periphery of the mass, with no enhancement at its center, a finding that was considered highly suggestive of a paraganglioma ( Figure 3 ). Fluorine-18 fluorodeoxyglucose positron emission tomography was also performed, demonstrating a highly metabolic mass ( Figure 4 ). Figure 2 Cardiac magnetic resonance. (1) Coronal: isointense mass in relation to the left atrial roof. (2) Two-chamber longitudinal: isointense mass in the left atrioventricular groove. (3,4) Axial: mass in relation to the aortic root and the pulmonary artery. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 3 Cardiac magnetic resonance. Delayed enhancement. Focal deposit of gadolinium in the periphery of the mass. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 4 Positron emission tomography with 18F-fluorodeoxyglucose (10 mCi). Hypermetabolic mass in the middle mediastinum. Images reproduced with permission from Clínica del Country-Bogotá-Colombia. The case was discussed with the heart team and other departments, such as endocrinology and oncology, concluding that the patient had a clear indication for surgery, with α- and β-blockade, high sodium intake, and adequate hydration before the procedure. However, given that there were doubts regarding the emergence of the left coronary artery and its pathway, coronary angiotomography was performed. The mass was found to surround the left main coronary artery, the proximal segment of the left anterior descending coronary artery, the circumflex coronary artery, and two septal arteries, as well as the great cardiac vein ( Figure 5, Figure 6, Figure 7 ). At that time, and because of these findings, the intervention was considered to be a high-risk procedure. Isotopic radiation with 131 I meta-iodine benzyl guanidine (MIBG) was considered as a palliative intervention, but this approach was rejected because of the risk for hypertensive crises of unpredictable severity. Another approach that was considered was the use of octeotride, but this alternative was not accepted by the multidisciplinary group, because there was a risk for irradiation of adjacent tissue, including the coronary arteries, with an unknown benefit. The risk/benefit assessment of this therapy did not favor the patient either, and surgery was thought to be the only option. Coronary angiography was done looking for a main feeding artery that could be embolized preoperatively to reduce the tumor size and intraoperative blood loss. However, embolization could not be done, because there were many small feeding arteries coming from the left main coronary artery ( Figure 8 ). The patient underwent mass resection, requiring a complete transverse arteriotomy of the ascending aorta, pulmonary trunk, and section of the superior vena cava. The mass was exposed using caudal traction and was found to be closely associated with the posterior wall of the ascending aorta, the pulmonary artery, and the left atrial roof, without infiltration of these structures. Involvement of the left coronary artery trunk was documented, which required ligation and revascularization of the anterior descending coronary artery and the circumflex coronary artery. The mass could be completely resected ( Figure 9 ). Figure 5 Coronary computed tomography. Mass surrounding the left main coronary artery and the proximal segment of the anterior descending and the circumflex coronary arteries. Figure 6 Coronary computed tomography. Mass surrounding the pulmonary artery. Figure 7 Coronary computed tomography. Mass located in the left atrioventricular groove. Figure 8 Coronary arteriography. Mass irrigated by multiple small vessels arising from the anterior descending coronary artery. Figure 9 Surgical specimen. Resected mass. The patient progressed well and was able to be extubated and have her vasopressor support discontinued. Follow-up echocardiography showed that systolic function was moderately affected, with an ejection fraction of 35% and diffuse hypokinesia, which was more pronounced in the anterior descending coronary artery territory. Because of these findings, new coronary angiography was performed, ruling out saphenous bridge compromise ( Figure 10 ). Further follow-up echocardiography showed improvement in systolic function, with an ejection fraction of 55% and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure ( Figure 11, Videos 3 and 4 ). Figure 10 Coronary angiography. Saphenous bridge patent to the anterior descending artery, without lesions. Figure 11 Transthoracic echocardiography. (1) Parasternal view in diastole: pericardial effusion. (2) Parasternal view in systole: akinesia of the basal anteroseptal segment. The pathology report of the surgical specimen described round and oval cells in an organoid pattern with fine chromatin nuclei and degenerative focal atypia ( Figure 12 ). These findings and the immunohistochemical studies were compatible with a paraganglioma. The genetic study showed a succinate dehydrogenase subunit B mutation. The patient progressed satisfactorily and was discharged. One month later, it was found that one of her father's cousins had a para-aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain. Figure 12 Round and oval cells, arranged in an organoid pattern, with degenerative focal atypia.\"}", "questions": ["What age group (e.g., adolescent, adult) does the patient belong to at the time of initial presentation?"], "ground_truth_arguments": ["22 - year - old"]}
{"id": "CaseReportBench:train-281", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case Presentation': \"Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment. A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5 th percentile), weight 3000 g (<5 th percentile), and head circumference 36.5 cm (5–10 th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance. Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative. The laboratory tests were as follows: serum sodium 102 meq/lit and serum k + level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1 . Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern. Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed. On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25 th percentile), weight 9.5 kg (10–25 th percentile) and head circumference 46 cm (25 th percentile); her neurodevelopment was appropriate for age.\"}", "questions": ["What types of corticosteroid therapies were given to the infant, and which clinical signs showed improvement as a result?", "How did the corticosteroid replacement therapy influence the infant's electrolyte balance and blood glucose during the early treatment period?", "How did bilirubin levels (total and direct) change over the course of therapy?", "What was the status of jaundice and stool color after treatment, and were there any recurrences during the subsequent six months?", "At the most recent follow‑up at 15 months of age, what health issues, if any, were reported for the patient?"], "ground_truth_arguments": ["Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting", "Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement . Electrolyte abnormalities and blood sugar was corrected during first week of treatment ( Na=130 and K=4.5 Meq / lit ) . One week later , the total and direct bilirubin declined to 5 and 2.5 mg / dl respectively . After one month , bilirubin levels and all of the liver function tests returned to normal , jaundice disappeared and acholic stools changed to normal pattern . In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed . On her most recent visit at the age of 15 months , the patient had no obvious problem ."]}
{"id": "CaseReportBench:train-97", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case presentation': 'A 50-year-old male with a history of MERRF syndrome was found to have serum prostate specific antigen of 9.45 ng per milliliter on routine screening. His urological history was significant for mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35. There was no erectile dysfunction with a normal International Index of Erectile Function score (24/25). His urinalysis was negative for pyuria or microscopic hematuria. The patient had been diagnosed with a sporadic form of MERRF as an adult after developing symmetric lipomas in his cervical region along with exercise intolerance and mild muscle atrophy. Despite having the common MERRF mitochondrial DNA mutation (A8344G) in his blood with multiple symmetric lipomatosis, his variant of MERFF did not include cognitive impairment nor seizures. 1 His past medical history was significant for a history of hypertension and hypercholesterolemia and his medications included levocarnitine, losartan, hydrochlorothiazide, and metoprolol. His surgical history included a tonsillectomy as a child and plastic surgery to remove neck lipomas. His family history was positive for lung and liver cancer in his mother. His physical examination showed normal vital signs and a body-mass index of 25 (height: 1.65 m, weight: 68 kg). Relevant findings included large, painless, symmetrical cervical lipomas ( Fig. 1 A and B), normal external genitalia, and a digital rectal examination revealing a soft prostate with good lateral definition bilaterally and an estimated volume of 30 cubic centimeters (cc.). A neurological examination was normal except for mild muscle weakness at the end of the day. Fig. 1 (A) Front and (B) lateral images of the patient with MERRF syndrome with characteristic cervical lipomas (with patient permission). Fig. 1 The patient underwent a 12-core ultrasound-guided transrectal prostate biopsy revealing grade group 2 adenocarcinoma (Gleason score 3 + 4 = 7) at the left mid for 9 mm (mm.) and right base for 5.5 mm., and grade group 1 (Gleason score 3 + 3 = 6) at the left base for 9 mm. Perineural invasion was present. His transrectal prostate ultrasound showed a prostate volume of 28.9 cc but no hypoechoic nodules. His calculated PSA density was 0.32 ng/ml/cc. After discussing all the treatment options, the patient chose a radical prostatectomy given his young age, high PSA density, moderate voiding dysfunction, and grade group 2 with significant involvement (9 mm. 5.5 mm., 9 mm.). Since proceeding with surgery was contingent upon neurology clearance, the patient was evaluated by his neurologist with a specialty in mitochondrial disorders. Given that his MERRF variant was only associated with mild myopathy, the patient was cleared for surgery with a willingness to accept a potentially higher risk of complications during intubation given his neck lipomas, as well as a theoretically higher risk of urinary incontinence or erectile dysfunction given the associated myopathy which characterizes the MERRF syndrome. The patient underwent a transperitoneal bilateral nerve-sparing robotic radical prostatectomy and pelvic lymphadenectomy without complications. There were no intubation-related complications; operative time was 150 minutes with an estimated blood loss 50 cc. The patient was discharged on postoperative day 1 without complications nor transfusions and his catheter was removed on postoperative day 7. His prostatectomy pathology was grade group 2, pathologic stage T2 with negative margins and lymph nodes. Based on the EPIC short form questionnaire administered four months after surgery the patient was free of pads and his PSA was less than 0.1. ng/ml. After 6 months, the patient could achieve intercourse with the aid of vardenafil on-demand with an International Index of Erectile function of 20/25. At last follow-up 52 months after surgery, the patient continues to be continent, has satisfactory sexual function using daily tadalafil, and his PSA remains less than 0.1 ng/ml.'}", "questions": ["What signs of reduced exercise capacity or muscle loss were documented in the patient's history?", "How is the patient's muscle weakness described, including the timing or circumstances of its occurrence?"], "ground_truth_arguments": ["exercise intolerance and mild muscle atrophy", "mild muscle weakness at the end of the day."]}
{"id": "CaseReportBench:train-280", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE REPORT': \"A young stocky built adult patient appearing in early twenties dressed in shirt and pant with a thick moustache and beard accompanied with parents walked inside psychiatry out-patient department (OPD) with a referral from plastic surgery OPD concerning gender affirmation surgery. Patient introduced self in a husky masculine voice as Ms. T, a 21-year old female patient and expressed desire to be named as Mr. T, in further conversation. On interview, parents reported patient to be their eldest daughter born of a non-consanguineous marriage following a full term normal vaginal delivery. Parents reported since early childhood, patient was tomboyish, more comfortable playing with boys, watching wrestling and never showed interest in dolls or playing with younger sister or girls at school. Patient used to wear shirt and skirt to school, but at home used to prefer wearing T-shirt and jeans. From adolescence onwards, patient started to gain weight, developed hirsutism and never attained menarche. Mother had to frequently remove patient's facial hairs by hair removing cream. Patient started to feel attracted towards females though never had any sexual contact. Patient started to develop strong disliking towards self being called as a female, withdrew self from female friends and interest in studies declined; but never verbalised these feelings to anyone. 17 years onwards, after completing high school patient started to express strong resentment. Thereafter, with parents consent patient started to dress as males, stopped removing facial hairs. From 18 years onwards, proclaiming self as Mr. T patient started to work as a salesman. Patient and parents were happy with the new desirable identity. Difficulties faced were using common urinals, feeling ashamed of getting the anatomical sex being disclosed and inability to study further or procure a white collared job because of high school certificate mentioning sex as female. Despite these problems, patient was more comfortable in male gender role and since past 2 years, started seeking help for gender affirmation surgery. Patient appeared to be of average intelligence and had no persistent aggressive, violent or criminal tendencies. There was no past history of taking any hormones exogenously. Examination revealed 65 kg weight, 160 cm height and 116/82 blood pressure. External body habitus was of male and external genitalia was of female. There were no apparent cushingoid features. Karyotyping showed 46XX pattern. Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X-ray were normal. Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17-OH progesterone and dehydro-epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test suggesting diagnosis of non-classical congenital adrenal hyperplasia.\"}", "questions": ["Describe any notable perinatal factors documented in the patient's history."], "ground_truth_arguments": ["born of a non - consanguineous marriage following a full term normal vaginal delivery."]}
{"id": "CaseReportBench:train-458", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}", "questions": ["When did the infant first exhibit recurrent hypoglycemia?", "At what point after delivery did the initial clinical signs appear?", "What was the timing of the first symptoms relative to birth?"], "ground_truth_arguments": ["shortly after birth"]}
{"id": "CaseReportBench:train-340", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["Was the infant younger than one month when they presented to the emergency department?"], "ground_truth_arguments": ["10 - day - old"]}
{"id": "CaseReportBench:train-40", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Cases': 'Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility, accompanied by congenital adrenal hyperplasia ( CAH ). Here are reported two cases of TART s that were referred to Kobe City Medical Center West Hospital for the treatment of infertility and testicular tumors.', 'Case 2': 'A 41 year old man was followed at the local clinic for polycythemia (hemoglobin: 18.0 g/dL; red blood count: 627 × 10 4 ; hematocrit: 53.1%) and hypertension. An abdominal CT scan for the examination of these conditions revealed the enlargement of the bilateral adrenal glands (Figure 5 ). The patient was referred to endocrinologists in the hospital for further investigation. The patient was seen to have obesity (height: 165 cm; weight: 79 kg; Body Mass Index: 29.0 kg/m²). The laboratory tests revealed an extremely high level of ACTH (316.4 pg/mL) and a relatively low level of cortisol (6.8 μg/dL). Although the patient did not have any family history of CAH, the CT findings regarding the adrenal glands, unbalanced pituitary–adrenal hormones, and high level of serum 17‐OHP (62.7 ng/mL) indicated the possibility of CAH. The difference from case 1 is that the first examination was made by endocrinologists, not urologists. The differential diagnosis was made before a testicular examination. The abnormality in the pituitary–gonadal hormonal status (FSH: <0.1 IU/mL; LH: <0.1 IU/mL; testosterone: 10.9 ng/mL; estradiol: 29 pg/mL) indicated the excessive secretion of adrenal androgens. Bilateral testicular tumors were identified in a scrotal ultrasound echo scan and then a urological consultation and several additional examinations were offered in order to rule out a germ cell tumor. At the physical examination, both testes had become slightly atrophied (right: 14 mL; left: 12 mL) (performed with a Prader orchidmeter) and no induration was palpated. All the serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 (Figure 6 A). The semen analysis showed azoospermia. A genetic diagnosis by PCR‐direct sequencing proved CAH due to 21‐hydroxylase deficiency due to CYP21A2 gene mutation. After 6 months of low‐dose, daily oral glucocorticoid therapy (0.5 mg/d), the serum FSH, LH, testosterone, and estradiol levels returned to normal levels (9.2 IU/mL, 1.8 IU/mL, 0.8 ng/mL, and <10 pg/mL, respectively). The polycythemia also improved to a Hb level of 15.2 g/dL. Sperm emerged (concentration: 3.4 × 10 6 /mL; motility: 26%), along with a size reduction in the adrenal hyperplasia and TART (Figure 6 B).', 'Case 1': \"A 41 year old man was referred to Kobe City Medical Center West Hospital, Kobe City, Japan, because of 2 years of infertility. At the physical examination, the patient's physical constitution was as follows (height: 1.58 m; weight: 65 kg; body mass index: 23.9 kg/m²). Both testes had become atrophied (9 mL) (performed with a Prader orchidmeter) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes (Figure 2 A). The semen analysis revealed oligoasthenozoospermia (volume: 2.6 mL; concentration: 7 × 10 6 /mL; motility: 14%). The hormonal examination revealed a normal hormonal status of serum follicle‐stimulating hormone (FSH) of 2.7 mIU/mL, luteinizing hormone (LH) of 1.3 mIU/mL, testosterone of 4.3 ng/mL, and estradiol of 13 pg/mL. All the serum markers for testicular tumors, including human chorionic gonadotropin, alpha‐fetoprotein, and lactate dehydrogenase, were within the normal range. The pelvic magnetic resonance imaging (MRI) scan showed irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image (Figure 3 ). An enhanced computed tomography (CT) scan revealed diffuse, irregular enlargement of both adrenal glands, with no finding in the testes (Figure 4 A,B). Bilateral testicular atrophy and bilateral enlargement of the adrenal glands without any other metastases did not seem to be typical for malignant testicular tumors. At this point, adrenal gland disease was suspected and an endocrinologist was consulted for further examination. In the endocrinological examination, both the serum ACTH and 17‐OHP levels were extremely high (69.3 pg/mL and 112 ng/mL, respectively). Genetic diagnosis by polymerase chain reaction (PCR)‐direct sequencing confirmed the 21‐hydroxylase deficiency due to CYP21A2 gene mutation (I‐172N mutation) and a low‐dose, oral glucocorticoid of 0.5 mg/d was started under the diagnosis of CAH. After 1 month of glucocorticoid therapy of 0.5 mg/d, the semen analysis revealed a significant change (concentration: 34 × 10 6 /mL; motility: 59%), along with normalization of the testicular size (right: 14 mL; left: 16 mL). The size reduction of the TART was identified by ultrasound (Figure 2 B). The hormonal status had not changed significantly from the pretreatment status (serum FSH: 2.8 mIU/mL; LH: 1.6 mIU/mL; testosterone: 3.2 ng/mL; estradiol: 18 pg/mL). After 2 years of glucocorticoid administration, the clinical pregnancy of his wife was established by using in vitro fertilization (IVF), resulting in the delivery of a female offspring (3650 g) who was confirmed as negative for CAH by serum 17‐OHP and 21‐deoxycortisol measurement.\"}", "questions": ["What conditions associated with congenital adrenal hyperplasia can contribute to male infertility?"], "ground_truth_arguments": ["Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility , accompanied by congenital adrenal hyperplasia ( CAH )"]}
{"id": "CaseReportBench:train-213", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case presentation': 'We report a case of a 40-year-old man with CAH/21-hydroxylase deficiency, who willingly interrupted Prednisolone therapy for years. In 2007 his left adrenal gland was removed and diagnosed with adrenocortical carcinoma. In 2012 CT scan ( Fig. 1 ) showed a tumor in the right adrenal gland, confirmed in 2013 by MRI, with retroperitoneal lymphadenomegaly. Serum hormonal screening showed high 17-OH progesterone and ACTH. The patient refused operation. He was referred to us from another hospital because of a synchronous progressive enlargement of bilateral testicular masses during substitutive medical therapy ( Fig. 2 ). Serum tumor markers at 12.09.2013: AFP 10.56 IU/mL (AFP 4.03 IU/mL 01.2012), hGT beta and CEA – not elevated, semen analyses: azoospermia. Considering the possibility of malignant testicular neoplasm, the patient underwent bilateral orchiectomy, because the frozen sections were interpreted as malignant tumors. Gross findings: right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds (0.1–1.5 cm). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin-α were positive in 50% of the cells. There were no mitotic figures on HE-staining (Ki 67 negative). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated. We excluded primary germ cell testicular tumors and anaplastic large cell lymphoma, metastatic nonsecreting pheochromocytoma. “TARTs” was the appropriate diagnosis. There was still suspicion for metastatic adrenocortical carcinoma because of the CT and MRI findings. In order to prove the diagnosis the patient agreed to the surgical removal of his right adrenal gland in 01.2014. Adrenocortical carcinoma was histologically diagnosed again at other hospital. We revised all slides and performed immunohistochemical analyses. In the left adrenal gland we found polygonal cells with mild nuclear pleomorphism, conspicuous nucleoli, abundant eosinophilic granular cytoplasm, some with lipochrome pigments, without mitotic activity (Ki 67 positive in <1% of nuclei). The clear cell component was about 26%. In CAH, marked diffuse hyperplasia of zona fasciculata is a result of ACTH stimulation. There is also a conversion of zona fasciculata cells into zona reticularis-type cells (lipid-depleted). The cells exhibited strong positive expression for vimentin, Melan A and inhibin. In the right adrenal gland microscopically we found fields and circumscribed but nonencapsulated nodules that protruded into the adjacent fat, consisting of fasciculata-type cells and nodules composed of zona reticularis-type cells with lipofuscin. Nuclear and cellular pleomorphism was more prominent than in the left adrenal gland. Mitoses necrosis, hemorrhage, sinusoidal, vascular and capsular invasion were not found. The required number of morphological criteria, according to Weiss and Aubert, to classify the lesion as carcinoma, were not met. 2 Revised diagnosis: CAH bilateral adrenal cortical hyperplasia of a diffuse and nodular type with multiple bilateral cortical nodules, pigmented nodules and congenital adrenal cytomegaly and bilateral TARTs revealing morphologically similar changes.'}", "questions": ["What age group does the patient belong to at the time of presentation?"], "ground_truth_arguments": ["40 - year - old"]}
{"id": "CaseReportBench:train-598", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["What sensory symptoms affecting the extremities are described in the case?", "What acute seizure‑related events and their immediate aftermath are reported?", "What findings were observed on brain magnetic resonance imaging?"], "ground_truth_arguments": ["tingling sensation in her hands", "seizure and postictal confusion", "Magnetic Resonance ( MR ) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES"]}
{"id": "CaseReportBench:train-552", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["What was the patient's heart rate and were any symptoms such as breathlessness, chest pain, syncope, or pre‑syncope reported?", "How was peripheral perfusion evaluated and what were the findings regarding the equality, regularity, and volume of peripheral pulses?", "What physical examination findings indicated the presence or absence of cardiomegaly, and what were the characteristics of the heart sounds and any murmurs heard?", "What did the chest X‑ray reveal about the cardiac silhouette and lung fields?", "What were the echocardiographic findings concerning cardiac structure, left ventricular dimensions, and systolic function?", "Describe the electrocardiogram results, including rhythm type, atrial and ventricular rates, QRS duration, QT interval, and calculated QTc.", "What changes in the patient's effort tolerance and appetite were observed after implantation of the pacemaker?", "Provide a detailed account of the circumstances surrounding the patient's death, including his position, activity, last communication with family, and condition when found unresponsive.", "How was the complete heart block identified on the ECG, and what specific atrial and ventricular rates were noted?"], "ground_truth_arguments": ["low heart rate", "not associated with breathlessness or chest pain. There were no episodes of syncope, pre - syncope", "peripheral perfusion was good and all peripheral pulses were felt equally", "regular pulses and a normal volume", "no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space", "His chest x - ray showed a normal cardiac silhouette", "Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits", "His electrocardiogram revealed complete atrio - ventricular disassociation with an atrial rate of 100 / min and a broad complex ventricular escape rhythm with a rate of 43 / minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds", "Electrocardiogram showing evidence of complete heart block with an atrial rate of 100 / minute and a broad complex escape rhythm with a ventricular rate of 43 / minute", "improvement in his effort levels as well as appetite", "his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive"]}
{"id": "CaseReportBench:train-152", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Patient': 'The patient was the second child of nonconsanguineous parents who was born after an uneventful pregnancy of 42 weeks. At birth, early findings comprised congenital hypotonia, low facial expression, and inverted feet. He was diagnosed with swallowing problems and gastroesophageal reflux. Dysmorphic features included brachyturricephaly, low-set ears, hypermetropia, facies myopathica, and hyperlaxity with arachnodactyly. Due to positive family history of minicore myopathy (his sister died with this condition at age 5 due to aspiration), an early muscle biopsy was performed. The initial histological findings suggested a possible multi/minicore disease. The patient developed chronic lactic acidemia (lactate 2.3–4 mmol/l, C: <2.1 mmol/l), 3-methylglutaconic aciduria (80 μmol/l, C: <18 μmol/mmol creatinine), and recurrent hypoglycemic episodes. Serum alanine levels (610 μmol/l, C: <450 μmol/l) and creatine kinase (CK) levels (500–800 U/l, C: 180 U/l) were moderately increased. No motor development was observed with regular physiotherapy; for further clarification of the diagnosis, a second muscle biopsy was performed at the age of 6 years. The biopsy results showed the characteristic picture of central core disease: electron microscopy detected abnormal, large mitochondria with crystalline inclusions and biochemical evidence of severe mitochondrial dysfunction (Table 1 ). Genetic studies including mitochondrial DNA sequencing, sequencing of the nuclear-coded structural complexes I and III genes, and POLG mutation analysis were all normal. A compound heterozygous RYR1 mutation in complementary DNA (cDNA) was found. The parents were heterozygous carriers (Wortmann et al. 2009 ). At age 9 years, while receiving regular physiotherapy, the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures. Further physical signs were bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees. He had no extraocular muscle anomalies and no exercise-induced myalgia. Table 1 Abnormal biochemical and genetic features Analyses performed Results Biochemistry ATP production nmol/h/mUCS (N 42–81) 4 Complex I mU/UCS (N 70–251) 58 Complex II mU/UCS (N 335–749) 312 Complex III mU/UCS (N 2200–6610) 725 Complex IV mU/UCS (N 810–3120) 483 Complex deficiencies I, II, III, IV Genetics Paternal mutation p. His581GlnfsX29 (exon 16) Maternal mutation p.Val14849Ile (exon 101) ATP adenosine triphosphate, UC unconditioned stimulus, N normal'}", "questions": ["What congenital neuromuscular signs were reported at birth (e.g., tone, facial expression)?", "What congenital foot abnormality was described in the patient?", "Which facial characteristics, including any myopathic facial appearance, were noted?", "What functional limitations and musculoskeletal abnormalities were documented in the patient?"], "ground_truth_arguments": ["congenital hypotonia, low facial expression, and inverted feet.", "facies myopathica", "the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures. Further physical signs were bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees"]}
{"id": "CaseReportBench:train-296", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'We report on a 5-year-old girl with a history of pink-stained urine as a newborn. Disease onset occurred in the tenth month of life. Her deciduous teeth sprouted with a red-brown color. She also suffered from episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation (fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas. Spleen enlargement was also observed. Urine porphyrins were extremely elevated to 16 μmol/dl with a predominance of coproporphyrins and uroporphyrins. However, the detailed concentration of each porphyrin was not analyzed. Severe cutaneous photosensitivity, blistering of light-exposed skin, history of pink-stained diapers and accumulation of porphyrins in the blood and various other tissues, particularly erythrodontia (fig. 1b ), suggested the diagnosis of CEP. The clinical and biochemical data of the patient are summarized in table 1 . With strict avoidance of UV and visible light, use of topical sunscreen, oral treatment with β-carotene and antibiotic for preventing bacterial infection of the skin, the bullae healed, leaving milia and hyperpigmented scars without the need of a blood transfusion. Mutation analysis of the UROS gene of the patient with CEP was performed. The DNA of exons 2–10 including splicing junctions of all exons was amplified by PCR and then sequenced. A single missense mutation corresponding to a G-to-T transversion (11,776 g>t) in exon 2 was found, leading to an amino acid change from valine at position 3 to phenylalanine (fig. 2 ). The result indicated that the patient was homozygous for this mutation. Then, we also analyzed the UROS genes of her parents who were shown to be heterozygote carriers of this mutation (fig. 3 ). Her brother had died of a disease similar to hers in terms of symptoms and abnormalities, suggesting that he had the same gene mutation (V3F). Conversely, on the basis of the pedigree analysis spanning three generations, no other symptomatic patients were found. To confirm the genotype-phenotype relationship, we constructed a pET-duet vector carrying mutated cDNA of UROS and transformed it into an Escherichia coli BL21 strain. The expression of UROS in bacteria was induced at 25°C. After purification of the expressed enzyme with nickel ion-beads (Qiagen Inc., Valencia, Calif., USA), the activity of mutated UROS (V3F) was compared with that of normal enzyme by the method of Wright and Lim. The specific activity of the mutated UROS was less than 16.1% that of the control.'}", "questions": ["What was the age of the patient at the time of presentation?"], "ground_truth_arguments": ["5 - year - old"]}
{"id": "CaseReportBench:train-416", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': \"A 21-year-old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009. Emergent colonoscopy was performed with the findings of (1) a large amount of blood in the rectum and sigmoid colon and (2) oozing from eroded rectal mucosa. Laboratory investigation revealed thrombocytopenia (platelets 10.3 × 10 4 / μl). Although the hemorrhage stopped spontaneously and did not occur again, the patient was referred to our hospital for further examinations. He had had no previous significant rectal bleeding. His past medical history was unremarkable except for occasional nasal bleeding during childhood. On physical examination, the abdomen was soft and flat; a non-tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin. Neurologic examination revealed no evidence of abnormalities. The laboratory data are summarized in table 1 . There were thrombocytopenia and slight leukocytopenia (platelets 6.7 × 10 4 /μl, white blood cells 3,180/μl). Other laboratory findings disclosed: total bilirubin 1.4 mg/dl (reference range 0.2–1.3), direct bilirubin 0.5 mg/dl (reference range 0–0.3), and prothrombin time activity 77.0% (reference range 90–130). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein-Barr virus and Helicobacter pylori ; however, there were no remarkable findings. Anti-DNA antibody test showed a titer of 1:40 (reference range <1:40). His platelet-associated immunoglobulin G (PAIgG) level was elevated to 166 ng/10 7 cells (reference range 9.0–25.0), however anti-platelet antibody (anti-platelet-binding IgG) was negative. Enhanced computed tomography (CT) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed (fig. 1a ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson's capsule (fig. 2 ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin-converting enzyme (ACE) concentrations (table 1 ), which is compatible with Gaucher disease. The enzymatic activity of leukocyte β-glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol/h/mg (reference range 56.76–74.85). We analyzed the seven common mutations (N370S, 84GG, F213I, IVS2+1, L444P, R463C and D409H) in the GBA gene as previously reported with the informed consent of the patient and found the compound heterozygous mutations L444P/D409H. Based on these results, we diagnosed the patient with Gaucher disease type 1. We started enzyme replacement therapy (ERT). 60 U/kg body weight imiglucerase, a macrophage-targeted recombinant human glucocerebrosidase, was injected every 2 weeks. Figure 1b shows the CT scan 5 months after ERT started. The liver and the spleen were sized down (liver: from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen: from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease, were also improved from 7.4 to 11.3 × 10 4 /μl and from 42.5 to 24.7 IU/μl, respectively (fig. 3 ).\"}", "questions": ["What acute gastrointestinal symptom did the patient present with at admission?", "What is the patient’s prior history concerning rectal bleeding?", "What were the abdominal physical examination findings, specifically regarding liver and spleen palpation and tenderness?", "What did imaging (e.g., CT) reveal about the size of the liver and spleen?"], "ground_truth_arguments": ["sudden rectal hemorrhage", "no previous significant rectal bleeding.", "abdomen was soft and flat; a non - tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin", "extremely enlarged liver and spleen."]}
{"id": "CaseReportBench:train-556", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 38-year-old female presented to the out-patient department with a 6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week. The patient gave no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits. On cutaneous examination, prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin-colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin-colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face. Fundus examination of both eyes showed dark brownish-red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks. 2D-echo and electrocardiogram were investigated to check for cardiac involvement but were normal. A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid-dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material (mucin). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition. Based on the clinical and histopathological findings, a diagnosis of PXE was made. The patient was started on oral and topical sunscreens, advised rigid eye protection to prevent accidental blunt trauma, and regular follow-up.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What diagnosis was concluded based on the clinical and histopathological findings?"], "ground_truth_arguments": ["Based on the clinical and histopathological findings , a diagnosis of PXE was made ."]}
{"id": "CaseReportBench:train-370", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Cases': 'Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility, accompanied by congenital adrenal hyperplasia ( CAH ). Here are reported two cases of TART s that were referred to Kobe City Medical Center West Hospital for the treatment of infertility and testicular tumors.', 'Case 2': 'A 41 year old man was followed at the local clinic for polycythemia (hemoglobin: 18.0 g/dL; red blood count: 627 × 10 4 ; hematocrit: 53.1%) and hypertension. An abdominal CT scan for the examination of these conditions revealed the enlargement of the bilateral adrenal glands (Figure 5 ). The patient was referred to endocrinologists in the hospital for further investigation. The patient was seen to have obesity (height: 165 cm; weight: 79 kg; Body Mass Index: 29.0 kg/m²). The laboratory tests revealed an extremely high level of ACTH (316.4 pg/mL) and a relatively low level of cortisol (6.8 μg/dL). Although the patient did not have any family history of CAH, the CT findings regarding the adrenal glands, unbalanced pituitary–adrenal hormones, and high level of serum 17‐OHP (62.7 ng/mL) indicated the possibility of CAH. The difference from case 1 is that the first examination was made by endocrinologists, not urologists. The differential diagnosis was made before a testicular examination. The abnormality in the pituitary–gonadal hormonal status (FSH: <0.1 IU/mL; LH: <0.1 IU/mL; testosterone: 10.9 ng/mL; estradiol: 29 pg/mL) indicated the excessive secretion of adrenal androgens. Bilateral testicular tumors were identified in a scrotal ultrasound echo scan and then a urological consultation and several additional examinations were offered in order to rule out a germ cell tumor. At the physical examination, both testes had become slightly atrophied (right: 14 mL; left: 12 mL) (performed with a Prader orchidmeter) and no induration was palpated. All the serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 (Figure 6 A). The semen analysis showed azoospermia. A genetic diagnosis by PCR‐direct sequencing proved CAH due to 21‐hydroxylase deficiency due to CYP21A2 gene mutation. After 6 months of low‐dose, daily oral glucocorticoid therapy (0.5 mg/d), the serum FSH, LH, testosterone, and estradiol levels returned to normal levels (9.2 IU/mL, 1.8 IU/mL, 0.8 ng/mL, and <10 pg/mL, respectively). The polycythemia also improved to a Hb level of 15.2 g/dL. Sperm emerged (concentration: 3.4 × 10 6 /mL; motility: 26%), along with a size reduction in the adrenal hyperplasia and TART (Figure 6 B).', 'Case 1': \"A 41 year old man was referred to Kobe City Medical Center West Hospital, Kobe City, Japan, because of 2 years of infertility. At the physical examination, the patient's physical constitution was as follows (height: 1.58 m; weight: 65 kg; body mass index: 23.9 kg/m²). Both testes had become atrophied (9 mL) (performed with a Prader orchidmeter) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes (Figure 2 A). The semen analysis revealed oligoasthenozoospermia (volume: 2.6 mL; concentration: 7 × 10 6 /mL; motility: 14%). The hormonal examination revealed a normal hormonal status of serum follicle‐stimulating hormone (FSH) of 2.7 mIU/mL, luteinizing hormone (LH) of 1.3 mIU/mL, testosterone of 4.3 ng/mL, and estradiol of 13 pg/mL. All the serum markers for testicular tumors, including human chorionic gonadotropin, alpha‐fetoprotein, and lactate dehydrogenase, were within the normal range. The pelvic magnetic resonance imaging (MRI) scan showed irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image (Figure 3 ). An enhanced computed tomography (CT) scan revealed diffuse, irregular enlargement of both adrenal glands, with no finding in the testes (Figure 4 A,B). Bilateral testicular atrophy and bilateral enlargement of the adrenal glands without any other metastases did not seem to be typical for malignant testicular tumors. At this point, adrenal gland disease was suspected and an endocrinologist was consulted for further examination. In the endocrinological examination, both the serum ACTH and 17‐OHP levels were extremely high (69.3 pg/mL and 112 ng/mL, respectively). Genetic diagnosis by polymerase chain reaction (PCR)‐direct sequencing confirmed the 21‐hydroxylase deficiency due to CYP21A2 gene mutation (I‐172N mutation) and a low‐dose, oral glucocorticoid of 0.5 mg/d was started under the diagnosis of CAH. After 1 month of glucocorticoid therapy of 0.5 mg/d, the semen analysis revealed a significant change (concentration: 34 × 10 6 /mL; motility: 59%), along with normalization of the testicular size (right: 14 mL; left: 16 mL). The size reduction of the TART was identified by ultrasound (Figure 2 B). The hormonal status had not changed significantly from the pretreatment status (serum FSH: 2.8 mIU/mL; LH: 1.6 mIU/mL; testosterone: 3.2 ng/mL; estradiol: 18 pg/mL). After 2 years of glucocorticoid administration, the clinical pregnancy of his wife was established by using in vitro fertilization (IVF), resulting in the delivery of a female offspring (3650 g) who was confirmed as negative for CAH by serum 17‐OHP and 21‐deoxycortisol measurement.\"}", "questions": ["What are the ages of the patients described in Case 1 and Case 2 at the time they presented for evaluation?"], "ground_truth_arguments": ["41 year old"]}
{"id": "CaseReportBench:train-183", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["What is the typical age range at which CTX is diagnosed, and what methods are commonly used to confirm the diagnosis?"], "ground_truth_arguments": ["diagnosed with CTX at age 27", "CTX at 38 years , which was confirmed by genetic testing .", "At the age of 14 years , she was formally diagnosed with CTX , which was confirmed by genetic testing ."]}
{"id": "CaseReportBench:train-476", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case report': 'An 11-year-old male had presented to the hospital with a history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4-5 years. There was no history of fever or localized pain. On examination, the blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg (75th-90th centile) and his height measured 138 cm (50th centile). Generalized skin hyperpigmentation was present. Systemic examinations were normal. Local examination revealed bilateral scrotal swelling with normal-appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia (testis length 3.5 cm, penile length 10 cm) and stage 3 for pubic hair. The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size (right and left testicular volume – 2.9 mL and 2.8 mL respectively) with multiple well-defined round to oval hetero-echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B). On screening abdominal sonography, a large well-defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity ( Figs. 3 A and B). Based on these findings, the possibility of testicular malignancy with adrenal metastasis was considered. Contrast-enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands (left>right) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C). Serum tumor markers (alpha-fetoprotein, LDH, and Beta hCG) were negative hence, the diagnosis was reconsidered for the possibility of testicular adrenal rest tumors in an undiagnosed case of congenital adrenal hyperplasia. Fig. 1 (A) Grayscale US of scrotum showing normal-sized right testis with heterogeneous appearance. (B) US image of bilateral testes with multiple nodules containing tiny calcific foci (black arrow). Fig 1 Fig. 2 (A) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. (B) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 (A) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions (white arrow). (B) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions (white arrow). Fig 3 Fig. 4 (A) Contrast enhanced computed tomography (CECT) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia (White arrows). (B) CECT pelvis axial section showing multiple enhancing nodules in the right testis (black arrow). (C) CECT pelvis axial section showing multiple enhancing nodules in left testis (black arrow). Fig 4 X-ray left wrist AP/lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq/L (normal range: 3.5-4.5 mEq/L), whereas the sodium level remained within normal limits at 140 mEq/L. There was a significantly heightened level of 17-hydroxyprogesterone at 1800 ng/dL (normal range: <110 ng/dL), accompanied by normal levels of lactate dehydrogenase (LDH), beta-human chorionic gonadotropin hormone (B-HCG), and alpha-fetoprotein (AFP). Additionally, the serum adrenocorticotropic hormone (ACTH) concentration was elevated, measuring 564 pg/mL (normal range: 7.2-63.3 pg/mL), while cortisol levels were diminished, measuring 5.7 µg/dL (normal range: 7-25 µg/dL). Dehydroepiandrosterone sulfate (DHEA-S) was measured at 5.25 µmol/L (normal range: ≤ 3.726 µmol/L), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng/dL (normal range: 31-65 ng/dL), and there was a reduced level of Inhibin B, measuring 71.1 pg/mL (normal range: 240-445 pg/mL). Collectively, these findings point towards a diagnosis of congenital adrenal hyperplasia. The patient is currently undergoing treatment with hydrocortisone and is on regular follow-up. The 3-month follow-up revealed clinical improvement with a reduction in testis size and decreased ACTH levels, indicating positive progress. Fig. 5 X-ray of left wrist AP and a lateral view showing accelerated bone age corresponding to approximately 18 years. Fig 5', 'Patient consent': 'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.'}", "questions": ["What treatment is the patient currently receiving, and what overall clinical improvements were noted at the three‑month follow‑up?"], "ground_truth_arguments": ["The patient is currently undergoing treatment with hydrocortisone and is on regular follow - up . The 3 - month follow - up revealed clinical improvement with a reduction in testis size and decreased ACTH levels , indicating positive progress ."]}
{"id": "CaseReportBench:train-163", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'2. Case presentation:': 'A 13-year-old girl with no history of medical or familial diseases presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache, which had started 10 days ago. Within the next few days following admission, the patient developed an attack of generalized tonic-clonic seizure associated with low-grade fever. On examination, the patient was confused in post ictal state. Otherwise, the neurological and general examination was unremarkable. Patient was hemodynamically stable. Urgent brain computed tomography (CT) scan showed brain edema ( figure 1 ). Cerebrospinal fluid (CSF) analysis, routine blood chemistry tests, blood culture, and serum electrolyte evaluation were performed. On a clinical basis, central nervous system infection was suspected and the patient started to receive acyclovir. Due to severe abdominal pain, abdominopelvic CT scan with contrast was done, which revealed marked distention of large bowel, and no definite air-fluid level or obstructing masses ( figure 1 ). The initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level: 108 milliequivalents per liter (mEq/L), potassium level: 2.7 mEq/L, total calcium level: 4.9 mg/dl, ionized calcium level: 3.5 mg/dl, magnesium level: 0.7 mEq/L, and phosphorus level: 2.1 mEq/L ( table 1 ). Within the next few days, the patient began to become agitated and developed generalized muscle pain despite proper correction of resistant hyponatremia with hypertonic saline 3%. In addition, the patient started to develop polyuria, and polydipsia, despite the normovolemic state, confirmed by clinical examination and central venous pressure monitoring. High suspicion to Bartter-like syndrome was raised as the renal tubular defect with increased renal loss of electrolyte was confirmed by the following laboratory investigation: urine osmolarity 277mOml/kg, serum osmolality 252 mmol/kg, serum chloride 73 mEq/L, and urinary Calcium/creatinine ratio 1.053 ( table 1 ). Within the next few days, she developed weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic. The rest of the examination was normal. Our opinion about the case changed and we had a rising concern about genetic disease. At that time, the whole-exome sequencing was sent abroad to CENTOGENE GmbH (Rostock, Germany) for genetic analysis. Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy (prolonged first time (F) wave latencies with reduced amplitude of compound motor action potentials). Unfortunately, the condition worsened till the patient became intubated and mechanically ventilated due to respiratory muscle involvement. The CSF examination showed cytoalbuminous dissociation, and this made the diagnosis more in favor of Guillain-Barre Syndrome (GBS). The patient received intravenous immunoglobulin (IV IG) (2gm per Kg divided over 5 days) with partial improvement. Due to the failure of multiple trials for weaning from mechanical ventilation, tracheostomy was performed. Genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase (HMBS) gene, which confirmed the diagnosis of autosomal dominant AIP ( figure 2 ). The patient received dextrose 25% and 2 doses of hemin 250 mg once daily for four days, 2 weeks apart followed by another dose after 2 months. There was a marked improvement regarding the weakness, and abdominal pain, and we managed to wean her from mechanical ventilation.'}", "questions": ["What statement in the document explains why intubation and mechanical ventilation were required because of impaired breathing muscles?"], "ground_truth_arguments": ["respiratory muscle involvement"]}
{"id": "CaseReportBench:train-131", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'Our case was a 1-year 5-month-old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath-holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium. The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby’s parents were consanguineous cousins. The father’s thalassemia status could not be elicited. On examination, the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm and the baby was conscious and alert. There was no jaundice or dehydration or abnormal odor. Arterial oxygen saturation (SpO 2 ) was 94%. The capillary refill time was between 3 s and 4 s. The heart rate was 146/min. The respiratory rate was 26/min. Non-invasive blood pressure was 73/44 (54) mm Hg. Respiratory system examination revealed normal chest movements with equal air entry on both sides. Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt. Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs. Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal. The eyes, musculoskeletal system, skin, and cardiovascular systems were normal. The baby was admitted for observation and investigations, and the initial differential diagnosis included alkaptonuria, myoglobinuria, hemoglobinuria, porphyria, and hemochromatosis. He had an under-current viral illness, which was managed symptomatically. The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g/dl (normal 10.5-14 g/dl), packed cell volume, mean corpuscular volume (MCV) and mean corpuscular hemoglobin were low at 31.9% (normal 32-42%), 68 fl (normal 72-88 fl), and 21.8 pg (normal 24-30 pg), respectively. MCV concentration was 32% (normal 31.5-34.5%) and red cell distribution width 17.1% (normal 11-16%). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high-pressure liquid chromatography (HPLC) revealed Hb A0 to be 80.4% and Hb A2 to be 6.1% (normal 2.40-3.60). The HPLC picture on correlation with the complete hemogram suggested β-thalassemia trait. DNA studies confirmed the beta globin gene defect of β-thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ-amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine. No abnormalities were detected on the electroencephalogram, leading us to believe that the breath holding spells were due to anemia. Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict’s reagent, strong alkali (filter paper impregnated with 10% sodium hydroxide turned black within 5 min when dipped into the urine) and ferric chloride (addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color). The urine of an alkaptonuric individual usually appears normal when passed. However, it starts to darken upon standing, and this is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Benedict’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test (with multistix) was negative excluding the role of glucose as reducing substance. For the qualitative assay of HA, to 0.5 ml of sample, a few drops of 10% ammonia was added followed by the addition of 3% silver nitrate solution. A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg/dl (normally HA is not present in urine). Parents’ urine was negative for HA. Due to the financial constraints, confirmatory diagnosis by DNA mutation analysis could not be carried out. The child was treated symptomatically, and he was given vitamin C (50 mg once a day for 3 months), low phenylalanine and tyrosine diet, and advised to monitor counts, get liver and renal function tests carried out every 2 weeks. On the request of his parents, the child was discharged after 3 days and advised to follow-up in the outpatient department (OPD). After 3 months post-therapy, his HA levels had not reduced. Currently, the baby is under follow-up every 6 months in the OPD.'}", "questions": ["What were the findings of the urine routine examination and abdominal imaging, and what major hematologic abnormalities were identified?", "What genetic analysis was performed on the beta‑globin gene and what did it reveal?", "What were the results of the serum electrolyte panel, serum bicarbonate, renal function tests, and liver function tests?", "What were the outcomes of the urine porphyrin estimation, serum lead level assessment, δ‑aminolevulinic acid testing, and detection of myoglobin or hemoglobin in the urine?", "How did the urine appearance change over time and after addition of Benedict’s reagent, a strong alkali, and ferric chloride?", "What were the results of the Benedict’s test and the glucose oxidase test on the urine, and what do they indicate about the presence of reducing substances?", "What color change was observed in the qualitative assay for homogentisic acid, and what were the quantitative findings for homogentisic acid in the urine?"], "ground_truth_arguments": ["The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g / dl ( normal 10.5 - 14 g / dl ), packed cell volume, mean corpuscular volume ( MCV ) and mean corpuscular hemoglobin were low at 31.9 % ( normal 32 - 42 % ), 68 fl ( normal 72 - 88 fl ), and 21.8 pg ( normal 24 - 30 pg ), respectively. MCV concentration was 32 % ( normal 31.5 - 34.5 % ) and red cell distribution width 17.1 % ( normal 11 - 16 % ). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high - pressure liquid chromatography ( HPLC ) revealed Hb A0 to be 80.4 % and Hb A2 to be 6.1 % ( normal 2.40 - 3.60 ). The HPLC picture on correlation with the complete hemogram suggested β - thalassemia trait. DNA studies confirmed the beta globin gene defect of β - thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child ’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ - amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine", "Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict ’s reagent, strong alkali ( filter paper impregnated with 10 % sodium hydroxide turned black within 5 min when dipped into the urine ) and ferric chloride ( addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color ).", "Benedict ’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test ( with multistix ) was negative excluding the role of glucose as reducing substance.", "A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg / dl ( normally HA is not present in urine )"]}
{"id": "CaseReportBench:train-436", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Radiological findings': 'Ultrasonographic examination revealed small hypoplastic uterus (6*7*3 ml) or atretic ovaries and adrenal glands had normal sizes. Clinical Course and Follow-up First, the patient hydrated with normal saline. Thereafter, considering hyponatremia, hyperkalemia, metabolic acidosis and decreased cortisol level and increased ACTH level, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) and sodium chloride was initiated. After replacement therapy, electrolyte abnormalities were corrected during first week and the patient was discharged from hospital with good clinical condition. She recommended referring for follow up. During follow-up, she had good clinical condition, with normal laboratory results except for 17 OHP which was lower during the period. At 6-years old, the patient referred with high blood pressure and adrenal insufficiency because of arbitrary drug discontinuation by mother. Renal Doppler ultrasonography and scan was performed which was normal. Regarding the recommendation of pediatric nephrologist fludrocortisone and sodium chloride was discontinued and treatment continued with hydrocortisone . Ultrasonography revealed the testicles in the abdominal cavity and uterus was not detected in pelvis. Orchiectomy was performed. Chromosome study showed 46XY pattern. On her most recent visit at the age of 6 years, the patient had no hyperpigmentation. Her height was 110 cm (10-25th percentile), weight 23 kg (75-90th percentile). Her last laboratory tests results were as follows; Na: 142 mmol/l, K: 4.5 mmol/l,17OHP: 0.1 ng/ml, ACTH: 22 pg/ml, Renin:50.8 pg/ml, Aldosterone: 105 pg/ml.', 'CASE REPORT': 'A 28-day-old phenotypic female infant was admitted to pediatric endocrinology clinic of Al-Zahra Hospital, affiliated to Isfahan University of Medical Sciences, because of poor weight gain and lethargy. She was a full-term infant with a birth weight of 3250 gr (50 th percentile), length of 51 cm (50 th percentile) and head circumference of 34 cm (50 th percentile).The patient had no perinatal problem. She was the 1 st child of nonconsanguineous parents. At the time of admission, she was lethargic without history of vomiting or diarrhea. There was not any familial history of similar presentation or features endocrine disease. She had no history of drug consumption except vitamin A+D.', 'Physical examination': 'She was lethargic, had depressed fontanele. She had mild dehydration and decreased skin turgor. In skin examination, she had mild hyperpigmentation, including oral cavity. External genitalia seemed normal female type with no ambiguity. There was not any abdominal or inguinal mass in abdominal examination. Her body weight, length and head circumference were 2900, 51 cm and 33.5 cm, all of them were beneath the 5 th percentiles. Her blood pressure was 60/40 mmHg, respiratory rate was 39/min, pulse rate was 112/min and body temperature was 37.1°C.'}", "questions": ["What surgical intervention was performed on the patient, including the type of surgery and the organ(s) involved?", "What were the notable aspects of the infant's initial presentation, including demographic information, presenting symptoms, and any relevant medical or family history?"], "ground_truth_arguments": ["Orchiectomy", "A 28 - day - old phenotypic female infant was admitted to pediatric endocrinology clinic of Al - Zahra Hospital, affiliated to Isfahan University of Medical Sciences, because of poor weight gain and lethargy. She was a full - term infant with a birth weight of 3250 gr ( 50 th percentile ), length of 51 cm ( 50 th percentile ) and head circumference of 34 cm ( 50 th percentile).The patient had no perinatal problem. She was the 1 st child of nonconsanguineous parents. At the time of admission, she was lethargic without history of vomiting or diarrhea. There was not any familial history of similar presentation or features endocrine disease. She had no history of drug consumption except vitamin A+D."]}
{"id": "CaseReportBench:train-5", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'2. Case Presentation': 'A 19-year-old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents (cousins). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally. On physical examination, there was diffuse palmoplantar keratoderma ( Figure 1 ). Intraoral examination revealed complete edentulous ridges with normal overlying mucosa. In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X-ray, and skull X-ray were normal. She was subsequently provided with artificial dentures and she was a candidate for mandibular bone graft from her skull and dental implants of lower jaw. Complete blood count and liver function tests were also normal. The patient was informed of the indication, and risks and benefits of fiberoptic nasal intubation under sedation. Preoperatively, after careful intravenous catheter insertion, she was premedicated with intravenous midazolam 1 mg and glycopyrolate 0.2 mg. Topical nasal vasoconstriction was achieved with oxymetazolin nasal drop and xylocaine spray 10% in both nostrils. Nasal oxygenation through the nasopharyngeal airway with 100% oxygen was started 3 minutes before the nasal intubation. The patient received a loading dose of dexmedetomidine (Precedex) 1 µg/kg infused over 10 minutes, followed by maintenance dose of Precedex (0.4 µg/kg/h). Gently, she was intubated by fiberoptic. During the awake nasal intubation, the patient’s SpO 2 remained between 97% and 100%. The heart rate varied from 82 to 96 beat/min. Fentanyl (1.5 µg/kg), propofol (2 mg/kg), and cisatracurium (0.15 mg/kg) were used for induction, and general anesthesia was maintained with Sevoflurane, 50% oxygen and 50% nitro oxide. Vital signs were stable during the surgery. Fentanyl (50 µg) and cisatracurium (2 mg) were repeated every 45 minutes. At the end of the surgery, the patient was extubated when she was fully awake and shifted to post anesthesia care unit (PACU) and had a recovery without any complication. Informed consent was taken from the patient regarding the publication of information in the journal. The patient reviewed the case and gave written permission for the authors to publish the report.', 'Case Presentation': 'We report a 19-year-old girl with palmoplantar hyperkeratosis who presented total loss of her teeth. She was candidate to mandibular bone graft and lower jaw dental implants under general anesthesia.'}", "questions": ["How is the overall condition of the patient's dentition described in the case presentation?", "What details are provided about the timing of loss of permanent and deciduous teeth relative to their eruption?", "What observations are reported regarding the condition of the edentulous ridges and the overlying oral mucosa?"], "ground_truth_arguments": ["complete loss of teeth by the age of 14 which", "permanent and deciduous teeth were lost after erupting normally", "complete edentulous ridges with normal overlying mucosa", "total loss of her teeth"]}
{"id": "CaseReportBench:train-207", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to house soiling and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. The environment consisted of two young adult humans with no children. They lived in a flat of 85 m 2, with two terraces of 5 m 2 each. There were three separated litter boxes at home, all of which were non-covered with low sides. The owners had used clumping, non-clumping, silica-based and soil-based litter during the months between the adoption (when the cat was 4 months old) and the first visit. One of the latrines always had clumping substrate. There were three food and three water troughs, all of them far from the latrines. The impression of the owners was that the cat eliminated where it was at any given moment. It eliminated many more times in front of the owner (90%) than when it was alone (10%). The cat never tried to cover its faeces or urine after depositions. Occasionally, the owners punished the cat verbally and physically, but only when it eliminated in front of them. The substrates used by the cat were ceramic tiles, the sofa and beds. It always adopted an emptying-body posture. Spots were always located on horizontal surfaces. The owners used bleach-based products in order to clean the spots, and just water in the case of the sofa and beds. Regarding the play-related problem, the owners said that the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘tried to bite, catch and scratch the air’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat’s behavioural history was unremarkable. The differential diagnoses of the house-soiling problem included problems with the litter trays, including insufficient number, incorrect type, competition with other cats for the latrines, incorrect location, acquired aversion, or inappropriate substrate; a preference for another location or substrate; a problem with preference acquisition (ie, because of a cognitive impairment, or a sensory impairment or an unavailability of appropriate latrines or substrate during the first few weeks of life); and marking behaviours. Finally, a medical illness can contribute to all of these problems or to be the main cause. 1, 2 We could rule out most of these problems after interviewing the owners. Firstly, it was unlikely that there was a problem with the litter tray because the number, type and location were correct. The locations were correct because the animal eliminated near the litter tray if it was there. Many different substrates had been used. Secondly, it was not a problem of preference because the cat eliminated in different locations and surfaces. The age of the animal, the distribution of the spots and the body posture during elimination ruled out marking behaviours. Alterations in play behaviours described by the owners could have been due to a cognitive impairment, and/or a sensory impairment (ie, blindness). Play behaviours depend on learning capability and sensory systems. 3 Additionally, an enriched environment is necessary to learn and display play behaviours in a proper manner. 4 In that case, the social and instrumental environment was good. Regarding elimination, a problem of substrate preferences acquisition was diagnosed. A cognitive impairment, a medical condition or both could have been the cause of the problem during the elimination habits acquisition. Moreover, cognitive impairment and some medical conditions also could explain the play-related behavioural problems. During the consultation, the physical examination was unremarkable; however, the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. A complete ophthalmological examination was performed by the ophthalmological service in order to rule out ocular diseases. No ophthalmological abnormalities were detected. Additionally, based on the behaviours at home described by the owners (the inability to find some toys, and the behaviour of ‘scratching and biting the air’), some degree of visual impairment was suspected but not confirmed with the neurological examination. The cat did not crash with objects either at home or at the consultation room. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits. The feline immunodeficiency virus/feline leukaemia virus test was negative. A thorax radiograph, abdominal ultrasound, brain magnetic resonance imaging (MRI; 0.2 T) and cerebrospinal fluid analysis showed no abnormalities. Although some small lesions could be missed with low-field MRI, we had to assume the absence of lesions obtained in the work-up. Thus, a degenerative condition such as a lysosomal storage disease, organic aciduria or mitochondrial encephalopathy was suspected. Samples of blood and urine were sent to the University of Pennsylvania School of Veterinary Medicine for metabolic screen tests. Amino acids, organic acids, carbohydrates, nitroprusside, ketone and mucopolysaccharide concentrations were analysed, as was α-mannosidase, β-mannosidase, fucosidase and hexosaminidase A and B activity. All of these were within normal limits. No treatment was prescribed for the neurological problem. The owners were given advice on correcting the soiling problem in the house using reward-based training with a clicker. During the first week, the clicker was conditioned by a food reward, and the entire floor was covered with newspaper. Each time that the cat eliminated, it was rewarded with a clicker and food. Newspaper was removed progressively. Three months later, the cat used a small newspaper-covered area to eliminate. This partial improvement suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability. After 3 months, the cat was referred to the neurology service again, in status epilepticus. Neurological findings, after the postictal phase, included a lack of bilateral menace response and cerebellar ataxic gait. A bilateral carpal valgus that had already been found in the first visit and a visible suture line in the posterior capsule of both crystalline lenses were also detected. The owners reported progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status (probably seizure activity). A symptomatic treatment with diazepam (1 mg/kg intrarectally only if seizures) and phenobarbital (2 mg/kg PO q24h) was started, with a very poor response. After 15 days of treatment, levetiracetam was added (10 mg/kg PO q8h) owing to an increase in seizure activity, with an initially good response. However, seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting <2 mins. After 2 years of treatment and a progressive worsening, the cat was euthanased. A complete necropsy was immediately performed. No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS. In order to rule out prion aetiology, a PrPsc inmunohistochemistry assay was performed, and the results were negative. Thus, congenital spongiform polioencephalomyelopathy (CSP) was diagnosed postmortem. Spongy vacuolation seen by light microscopy in the neural tissue is defined as spongy degeneration, and may take the form of vacuoles within processes of the neuropil, vesiculation of myelin sheaths, or swelling of astrocyte or oligodendrocyte cytoplasm. 5 A congenital problem, retrovirus infection and prion disease have been suggested as possible aetiologies. 6 – 10 Congenital spongiform degeneration of the grey matter has been previously described in a few cases of cats; 6 – 8 however, the cause remains still unknown. Common clinical signs include gait alteration, seizures, blindness, bilateral cataracts, behavioural changes and cranial nerve alterations. These signs appear during very early stages of development (just after birth), with a progressive fatal outcome in a few days or months. Behavioural signs are poorly described in animal science literature. 6 – 8 Although the degeneration usually affects diffusely all the grey matter, the behavioural alterations and the evolution of the clinical signs depend on the affected area of the brain in each case. Nevertheless, the clinical signs do not always correlate with the degree of the histological lesions. A spongy degenerative problem of grey matter has also been described in humans, and occurs in isolated cases and in sibs. 11 – 13 In all of human cases reported, the problem appears early in infancy and the outcome is always fatal. All the affected children show learning disabilities (ie, retarded speech development) during the early periods of infancy. Additionally, they rapidly develop neurological signs, especially seizures. The clinical findings and neuropathological changes are very similar in humans and the present case. There are no studies regarding degeneration of grey matter and its effect on learning ability in animals. However, other neurodegenerative problems (ie, lysosomal storage diseases) and problems that lead to structural abnormalities of the forebrain (ie, hydrocephaly) may be correlated with learning disabilities in animals and humans. 14 – 17 The acquisition of the elimination habits occurs during the first weeks of a kitten’s life. Most kittens naturally seek out sand-like materials for elimination purposes. However, the preference for a substrate needs to be learnt during those first weeks of age. Learning disabilities and/or sensory impairments could modify the acquisition of these habits.'}", "questions": ["What elimination and play behavior abnormalities were reported by the owners?", "Which specific play behaviors indicated difficulty interpreting other cats’ cues or interacting with objects?", "What neurological findings were observed on the initial examination, especially concerning gait and visual reflexes?", "How was visual function evaluated both clinically and based on the owners’ observations, and what conclusions were drawn about possible visual impairment?", "Which central nervous system imaging and cerebrospinal fluid analyses were performed, and what were their results?", "How did the reward‑based clicker training affect the cat’s elimination behavior, and what does this reveal about its learning capacity?", "Describe the seizure presentation that led to the second neurology referral, including the initial severe episode and the subsequent seizure pattern.", "What progressive gait abnormalities and other episodic behaviors did the owners note after seizure onset?", "What macroscopic observations were reported at necropsy?", "What microscopic diagnosis was made from CNS histology, and how were the lesions characterized?", "What evidence was reported regarding the cat’s interaction with objects that informs its visual abilities?", "During follow‑up, what was the reported frequency and typical duration of seizures?", "How did the owners characterize the cat’s ability or inability to engage in normal play activities?"], "ground_truth_arguments": ["house soiling and a play - related problem.", "did not know how to play.", "the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘ tried to bite, catch and scratch the air ’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat ’s behavioural history was unremarkable", "moderate and hypermetric ataxic gait, and a bilateral lack of menace response", "based on the behaviours at home described by the owners ( the inability to find some toys, and the behaviour of ‘ scratching and biting the air ’ ), some degree of visual impairment was suspected but not confirmed", "The cat did not crash with objects either at home or at the consultation room", "brain magnetic resonance imaging ( MRI; 0.2 T ) and cerebrospinal fluid analysis showed no abnormalities.", "suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability.", "status epilepticus", "lack of bilateral menace response and cerebellar ataxic gait", "progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status ( probably seizure activity )", "seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting < 2 mins", "No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS."]}
{"id": "CaseReportBench:train-3", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'Our case was a 1-year 5-month-old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath-holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium. The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby’s parents were consanguineous cousins. The father’s thalassemia status could not be elicited. On examination, the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm and the baby was conscious and alert. There was no jaundice or dehydration or abnormal odor. Arterial oxygen saturation (SpO 2 ) was 94%. The capillary refill time was between 3 s and 4 s. The heart rate was 146/min. The respiratory rate was 26/min. Non-invasive blood pressure was 73/44 (54) mm Hg. Respiratory system examination revealed normal chest movements with equal air entry on both sides. Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt. Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs. Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal. The eyes, musculoskeletal system, skin, and cardiovascular systems were normal. The baby was admitted for observation and investigations, and the initial differential diagnosis included alkaptonuria, myoglobinuria, hemoglobinuria, porphyria, and hemochromatosis. He had an under-current viral illness, which was managed symptomatically. The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g/dl (normal 10.5-14 g/dl), packed cell volume, mean corpuscular volume (MCV) and mean corpuscular hemoglobin were low at 31.9% (normal 32-42%), 68 fl (normal 72-88 fl), and 21.8 pg (normal 24-30 pg), respectively. MCV concentration was 32% (normal 31.5-34.5%) and red cell distribution width 17.1% (normal 11-16%). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high-pressure liquid chromatography (HPLC) revealed Hb A0 to be 80.4% and Hb A2 to be 6.1% (normal 2.40-3.60). The HPLC picture on correlation with the complete hemogram suggested β-thalassemia trait. DNA studies confirmed the beta globin gene defect of β-thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ-amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine. No abnormalities were detected on the electroencephalogram, leading us to believe that the breath holding spells were due to anemia. Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict’s reagent, strong alkali (filter paper impregnated with 10% sodium hydroxide turned black within 5 min when dipped into the urine) and ferric chloride (addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color). The urine of an alkaptonuric individual usually appears normal when passed. However, it starts to darken upon standing, and this is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Benedict’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test (with multistix) was negative excluding the role of glucose as reducing substance. For the qualitative assay of HA, to 0.5 ml of sample, a few drops of 10% ammonia was added followed by the addition of 3% silver nitrate solution. A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg/dl (normally HA is not present in urine). Parents’ urine was negative for HA. Due to the financial constraints, confirmatory diagnosis by DNA mutation analysis could not be carried out. The child was treated symptomatically, and he was given vitamin C (50 mg once a day for 3 months), low phenylalanine and tyrosine diet, and advised to monitor counts, get liver and renal function tests carried out every 2 weeks. On the request of his parents, the child was discharged after 3 days and advised to follow-up in the outpatient department (OPD). After 3 months post-therapy, his HA levels had not reduced. Currently, the baby is under follow-up every 6 months in the OPD.'}", "questions": ["What observations were documented regarding the presence or absence of abnormal skin odor?", "What history was reported concerning fever, rash, or related symptoms in the patient?", "What findings were noted about jaundice, dehydration, and any abnormal odor during the physical examination?", "How were the skin and cardiovascular systems described on clinical examination?"], "ground_truth_arguments": ["no abnormal odor of the skin", "no history of fever, rash,", "no jaundice or dehydration or abnormal odor", "skin, and cardiovascular systems were normal."]}
{"id": "CaseReportBench:train-407", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A 63-year-old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A-C ) was referred to our hospital due to an abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm ( Fig. 1D ). He had a history of hypertension for 5 years and a smoking habit (10 cigarettes/day). Coronary angiography revealed mild to moderate coronary atherosclerotic lesions ( Fig. 1E and F ). He was initially suspected of having FH based on his physical findings as well as the presence of AAA with a modestly elevated LDL cholesterol level (166 mg/dL). He was born to consanguineous parents (second cousins). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis. Recessive inherited disease was speculated at this point, so we investigated his genetic background using whole-exome sequencing, assuming a recessive form of inheritance. The mean depth was 99.9× per base across the whole exome. The percentage of on-target reads was 84.6%. Also, the coverage rate of target coding lesions (10×) was 99.0%. Bioinformatics analyses and segregation pattern matching followed by exome sequencing were performed for the patient to identify causative variants. The number of aligned variants in the patient that passed the standard quality control was 142,508. Of those, 15,335 were missense, nonsense, splice site, and frameshift variants. After removing “common” variants ( 10 ), 3,042 variants were detected. Subsequently, filtering against the segregation pattern assuming the recessive form of inheritance with the use of an in silico annotation prediction tool (scaled C-score >20) reduced the candidate variants to homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene (c.410G>A or p.Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ). Accordingly, an increased serum level of cholestanol was found (5.2 μg/mL, reference range 1.62-3.08). The patient did not show any neuropathy, although T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging showed periventricular white matter. Other classical phenotypes of CTX, such as juvenile cataract, chronic diarrhea, and intellectual disability, were not found. Endovascular repair (EVAR) was successfully performed for the treatment of his saccular type AAA. Atorvastatin 10 mg was used to reduce his LDL cholesterol, although chenodeoxycholic acid was not used due to the lack of neuropathy.'}", "questions": ["What ocular features typical of cerebrotendinous xanthomatosis were reported as absent in the patient?", "What gastrointestinal manifestations typical of cerebrotendinous xanthomatosis were reported as absent in the patient?", "What neurocognitive or intellectual impairments typical of cerebrotendinous xanthomatosis were reported as absent in the patient?", "Which classical phenotypes of cerebrotendinous xanthomatosis were explicitly noted as not present in the case report?"], "ground_truth_arguments": ["juvenile cataract, chronic diarrhea, and intellectual disability, were not found"]}
{"id": "CaseReportBench:train-387", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': \"The patient was a 37-year-old female, of 157 cm in height and 45 kg in weight. She was transferred to our department from a local hospital due to psychiatric features (both agitated behavior and auditory hallucinations), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic-clonic seizures. She had a long history of episodic migraine-like headaches and progressive bilateral hearing loss for 3 years. However, she did not take any medication. Her vital signs showed a normal body temperature of 36.8 °C, a hypotension of 90/56 mm Hg and pulse at 72 beats per minute. Because of the patient's psychiatric symptoms and application of sedative after seizure attacks, she could not cooperate with physical examination. The laboratory data showed high anion gap metabolic acidosis with elevated levels of lactate and pyruvate. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were decreased. Her TSH level was low at 0.26 mU/L (normal range 0.35–5.5 mU/L), and FT4 concentration was 7.56 pmol/L (normal range 10.2–31 pmol/L). Both serum free and total triiodothyronine (FT3 and TT3) were significantly lower than normal range. FT3 concentration was 2.28 pmol/L (normal range 3.5–6.5 pmol/L), and TT3 concentration was 0.6 nmol/L (normal range 1.2–3.4 nmol/L). Moreover, elevated titers of serum anti-thyroglobulin and anti-thyroid microsomal antibodies were detected. Cerebral spinal fluid (CSF) studies were normal for cell counts and biochemistry, and negative for culture. CSF IgG index was 0.48 (normal range ≤ 0.7), and oligoclonal bands (OB) was negative. Computed tomography (CT) scan showed lesions of hypodense in the left temporal and parietal lobe, with brainstem and cerebellar atrophy ( Fig. 1 A). No evidence of subarachnoid or intracerebral hemorrhage. Vascular imaging of the cervical and cerebral arteries by CT angiography excluded the possibility of cerebrovascular disease ( Fig. 1 B). However, CT images were not conclusive to differentiate between the infectious or metabolic lesion. On day 5, brain magnetic resonance imaging MRI (3.0 T) revealed a hypointensity lesion in the left temporal-parietal lobe on T1 weighted image ( Fig. 2 A), and increased signal intensity in the same region on FLAIR sequences ( Fig. 2 B) with a clearly restricted diffusion ( Fig. 2 C). The signal intensity on ADC sequence was mildly reduced ( Fig. 2 D). No obvious enhancement was found on Gd-DTPA enhanced images ( Fig. 2 E). MR spectroscopy was carried out as well. Compared to the ipsilateral normally appearing area ( Fig. 2 F), there was a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) with decreased NAA spectrum and reduced NAA/Cr ratio ( Fig. 2 G). The change of the spectrum reflected the severity of metabolic disorders, suggesting the local accumulation of lactic acid and disturbance of hypoxic processes. Fig. 1 CT scan showed lesions of hypodense in the left temporal and parietal lobe (Panel A). Three-dimensional reconstruction of CT vessel images (Panel B). Fig. 1 Fig. 2 Brain MRI (3.0 T) revealed a hypointense lesion in the left temporal and parietal lobe on T1 (Panel A), and increased signal intensity in the same region on Flair (Panel A) image with a clearly restricted diffusion (Panel C). The signal intensity on ADC sequence is mildly reduced (Panel D). No obvious enhancement was found on Gd-DTPA enhanced images (Panel E). Compared to the ipsilateral normally appearing area (Panel F), MR spectroscopy presented a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) (Panel G). Panels f and g are the molecular findings of metabolites respectively. Fig. 2 An electroencephalogram was performed on day 7 and displayed bilateral slow wave activities. Brainstem auditory evoked potential (BAEP) showed the bilateral sensorineural hearing loss. All the clinical and radiological findings were suggestive of mitochondrial disease. The final diagnosis of MELAS syndrome was confirmed by genetic analysis. The patient's peripheral blood leukocytes was detected by restriction fragment length polymorphism (RFLP) and revealed a mitochondrial DNA (mtDNA) mutation at A3242G point ( Fig. 3 ). Fig. 3 Mitochondrial DNA (mtDNA) mutation at A3242G point. Fig. 3 Her medications included L-arginine, phenobarbital, co-enzyme Q and levothyroxine substitution therapy. The patient's condition continuously improved, and was discharged on day 23. Six months following discharge, this patient had no further seizure.\"}", "questions": ["What diagnostic test confirmed the final diagnosis of MELAS syndrome?"], "ground_truth_arguments": ["The final diagnosis of MELAS syndrome was confirmed by genetic analysis ."]}
{"id": "CaseReportBench:train-12", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["What is the mother's obstetric history in terms of gravida and para?", "At what gestational age did the mother first present for antenatal care in this pregnancy?", "Which number pregnancy is this for the mother (e.g., first, second, etc.)?", "What were the overall findings of the maternal serum screening for estriol, AFP, and hCG?", "What findings did the Level II ultrasound performed after 21 weeks' gestation show regarding fetal structural abnormalities, especially the adrenal glands and genitalia?", "What were the birth weight, sex, mode of delivery, Apgar scores, and gestational age at delivery of the second baby?"], "ground_truth_arguments": ["G2P1", "17 weeks ' gestation", "second pregnancy", "Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median ( MoM ) with low alpha - fetoprotein ( AFP ) and human chorionic gonadotropin ( hCG ) level, 0.6 MoM and 0.52 MoM, respectively", "Level II ultrasonography after 21 weeks ' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia", "A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks ' gestation"]}
{"id": "CaseReportBench:train-399", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'A 3-year-old boy was admitted to our emergency department because of convulsions and unconsciousness. He had been diagnosed as 21-hydroxylase deficiency at birth. He had been taking oral steroid (hydrocortisone) replacement therapy since then. His parents had stopped steroid therapy without the knowledge of the physician 3 days before the symptoms started. They were admitted to our hospital 6 hours after the onset of the symptoms. He was in coma and had seizures on admission. Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg/dl and white blood cell (WBC) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies. Intravenous hydrocortisone treatment was initiated. Electroencephalography showed focal epileptic activity. Routine brain MRI was performed. Diffusion weighted images (DWI) and susceptibility weighted images (SWI) were also obtained in order to detect ischemia and hemorrhage. T2-weighted and fluid attenuated inversion recovery (FLAIR) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical-subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical-subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient (ADC) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto-occiptal cortical-subcortical regions due to hypoxia and hypoglisemia. We obtained follow-up brain MRI on fifth, twelfth, and twentieth days once the treatment has started. DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae.'}", "questions": ["What acute neurological symptoms did the patient exhibit on presentation?", "What findings were reported on the electroencephalography performed during the acute phase?", "What abnormalities were described on the initial brain MRI, and what was the presumed underlying cause?", "What changes were observed on the follow‑up brain MRI performed on day 20?", "What neurological sequelae were noted in the patient after treatment?"], "ground_truth_arguments": ["convulsions and unconsciousness", "coma and had seizures", "Electroencephalography showed focal epileptic activity", "T2 - weighted and fluid attenuated inversion recovery ( FLAIR ) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical - subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical - subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient ( ADC ) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto - occiptal cortical - subcortical regions due to hypoxia and hypoglisemia", "DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae"]}
{"id": "CaseReportBench:train-460", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case Presentation': 'A 17-year-old intellectually disabled boy was admitted to our neurology clinic due to an abnormality in his hand and difficulty in walking. He had a feeling of fear and trembling of his legs when climbing the stairs. His symptoms had begun when he was 4 years old and worsened until his parents noted and brought him to the clinic. He had diarrhea and jaundice during infancy and underwent phototherapy 3 times until the jaundice was completely resolved. Also, he had bilateral cataracts at the age of 12. At the age of 14, he had a car accident that caused a fracture in his skull. He had no history of cardiovascular or pulmonary diseases, and there was no genetic disorder in his family history. He was the fourth child of the third-degree consanguineous marriage and was born at term after a normal pregnancy, and his development was normal. At the time of admission to the clinic, his weight was 54 kg (11.70 percentile), height was 158 cm (1.07 percentile), and head circumference was 56 cm. Physical examination revealed ataxia, dysarthria, and spastic paraparesis with pyramidal signs more prominent on the right lower extremity. Eye examination and other neurological tests were performed because of his symptoms such as visual impairment, peripheral neuropathy, hallucinations, depression, and delusion and yielded negative results. There was no sign of palpable xanthoma in any of his tendons even in Achilles tendon. In the examination of his right hand, the fourth and fifth interphalangeal joints were flexed, and the third and fifth metacarpophalangeal joints were extended, which was found to be the result of presence of small xanthoma in the tendons of the right hand ( Figure 1 ). Electromyography and nerve conduction velocity (EMG/NCV) revealed no evidence of myopathy or neuropathy, and the motor and sensory conduction velocities were normal. Laboratory tests showed a normal cholesterol level in the serum (162 mg/dL) and a normal total serum bile acid level (10 µmol/L). Other laboratory test results are shown in Table 1 . Brain magnetic resonance imaging (MRI) demonstrated diffuse and focal cerebral and cerebellar white matter abnormalities ( Figure 2 ). The genetic study was performed by the next-generation sequencing (NGS) method, and the results were confirmed by the Sanger sequencing method. The apparent homozygous variants in the NM_000784.4(CYP27A1) : c.803G>A (p.Trp268*) and NM_032382.5(COG8) : c.1073G>A (p.Arg358Gln) in the CYP27A1 and COG8 genes were found which are pathogenic based on American College of Medical Genetics (ACMG) classification. 9, 10 Therefore, our patient was diagnosed with CTX and a mutation on COG8 gene . In due course, we started CDCA 810 mg daily (15 mg/kg/day). In a 3-month follow-up, he had a cholesterol level of 96 mg/dL and a bile acid level of 4 µmol/L which both were normal, and the symptoms had been under control. Due to the absence of seizures, he did not receive any additional treatment. Since then, he was followed every 3 months with a physical examination and laboratory tests including cholesterol level. In addition, the patient’s family was consulted on how to respond correctly to his needs, due to his intellectual disability.'}", "questions": ["What medication was initiated for the patient, and what was the general dosing regimen (e.g., dose range and frequency)?"], "ground_truth_arguments": ["In due course , we started CDCA 810 mg daily ( 15 mg / kg / day ) ."]}
{"id": "CaseReportBench:train-149", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 24‐year‐old woman was admitted to our hospital with mildly impaired consciousness and myoclonus in the extremities. She had been diagnosed with MELAS at 21 years of age. Genetic testing revealed a 3271 T>C transition in the MT‐TL1 gene, clinically confirming the diagnosis of MELAS. After admission to hospital, neurological examination showed myoclonic movement in the extremities, mandible, and trunk. Muscle weakness was detected in the upper and lower limbs bilaterally. A laboratory examination showed increased serum pyruvic acid (2.1 mg/dL) and lactate (75 mg/dL). Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging (Fig. 1 ). Antiepileptic drugs levetiracetam, perampanel, lacosamide, and clobazam were initiated. L‐arginine, coenzyme Q10, and L‐carnitine aimed at supporting mitochondrial energy production were given simultaneously. As the impaired consciousness and myoclonus persisted for 2 weeks, we undertook brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex. Electroencephalography revealed high‐amplitude slow and spiked waves. We diagnosed the patient with non‐convulsive status epilepticus. To control the seizures, propofol was given at a dose of 2.7 mg/kg/h for 12 h and then increased to 5.4 mg/kg/h, with midazolam added at a dose of 2 mg/h. On day 5, the urine appeared brown and arterial blood gas revealed metabolic acidosis (pH 7.261, pCO 2 33.0 mmHg, HCO 3 - 14.4 mmol/L, and lactate 99 mg/dL). Creatinine kinase was elevated at 20,999 U/L. The patient was diagnosed with PRIS. She was transferred to the intensive care unit (ICU) on day 19 of hospitalization. On admission to the ICU, the vital signs were as follows: body temperature, 39°C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths/min; and SpO2, 99% (FiO 2 40%). Laboratory findings showed metabolic acidosis (lactic acid, 99 mg/dL; pyruvic acid, 0.92 mg/dL), creatinine kinase 29,560 U/L, and myoglobin 9,845 ng/mL. We treated her with interruption of propofol and continuous hemodiafiltration for metabolic acidosis. We continued coenzyme Q10, L‐carnitine, and L‐arginine for mitochondrial support for MELAS and antiepileptic drugs including levetiracetam, perampanel, lacosamide, and clobazam. After concurrent treatment of PRIS and MELAS, metabolic acidosis and creatinine kinase gradually decreased after reaching 59,000 IU/L on day 2 of ICU admission. Continuous hemodiafiltration was discontinued on day 11. Tracheostomy was carried out because i.v. midazolam treatment was prolonged to control the status epilepticus. Mechanical ventilation was discontinued on day 25 (Fig. 2 ). After rehabilitation, the patient was discharged on foot.', 'Case Presentation': 'A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus. To control the non‐convulsive status epilepticus, propofol was administered. Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated. The patient was diagnosed with PRIS. We treated her with interruption of propofol. She required mechanical ventilation for 25 days. After rehabilitation, she recovered and was discharged.'}", "questions": ["What demographic details are provided for the patient?", "What mitochondrial disorder had been previously identified in the patient?", "What clinical signs or symptoms were observed that led to hospital admission?", "To which medical facility was the patient admitted?"], "ground_truth_arguments": ["A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus."]}
{"id": "CaseReportBench:train-531", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What diabetes-related information is documented for the patient?"], "ground_truth_arguments": ["poorly controlled type 2 diabetes mellitus"]}
{"id": "CaseReportBench:train-519", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': 'We present the case of a 28‐year‐old Mexican woman who came to our clinic because she had been experiencing recurring episodes of intense abdominal pain, weakness in her upper and lower extremities, uncontrollable vomiting, and insomnia since the age of 17. These symptoms required frequent visits to the emergency department. Despite undergoing normal biochemical and imaging tests, not responding to pain relief medications, and even undergoing abdominal surgery for suspected acute appendicitis, her symptoms persisted. After enduring nearly 3 years of almost daily symptoms, an episode of elevated urine PBG during a crisis finally confirmed the diagnosis of AIP. Treatment with hematin derivatives (Normosang®, Panhematin®) was initiated, resulting in partial improvement. However, subsequent years witnessed progressively severe crises, some accompanied by paralysis and kidney injury. Remarkably, elevated urine PBG was even detected during asymptomatic periods. Notably, her first cousin was also diagnosed with AIP and had a similar clinical presentation. A molecular genetic study was conducted at a reference center in Belgium. All coding exons (1, 3–15), including parts of the adjacent intronic sequences and regions of the 5′‐ and 3´‐UTR of the HMBS gene, were PCR‐amplified from genomic DNA. The amplicons underwent direct sequencing using capillary electrophoresis and the BigDye technology (Applied Biosystems). Data alignment and comparison with the wildtype sequence (NM_000190.3) were performed using the GenBank Database. This analysis revealed a heterozygous state mutation, c.457C > T (p.Q153, exon 9, HMBS gene). At the age of 38, she enrolled in a clinical trial for Givosiran, an RNA interference therapeutic targeting ALAS1 mRNA. Remarkably, she exhibited a notable response to the treatment and continued it even after the trial. Over the past years, her symptoms have been sporadic, and she has not required hospitalization. The patient is now 42 years old.'}", "questions": ["What were the characteristics and frequency of the patient's abdominal pain episodes, and how was the vomiting described?"], "ground_truth_arguments": ["recurring episodes of intense abdominal pain", "uncontrollable vomiting"]}
{"id": "CaseReportBench:train-89", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 6-year-old male child, first born of third-degree consanguineous parents, presented with scaly lesions on skin over both upper and lower limbs since day 5 of life, global developmental delay and stiffness of all limbs. The child was delivered by cesarean section. He was admitted in neonatal intensive care unit for neonatal jaundice. He had recurrent episodes of generalized tonic clonic seizures since the age of 1½ years with a total of 8 episodes so far (last episode at the age of 4 years). On examination, diffuse large brown colored diamond shaped adherent scales were present over the skin of all limbs implicating generalized ichthyosis with relative sparing of face. Seborrheic dermatitis of scalp was present. Diffuse hyperpigmented macules were present over the flexural areas and abdominal skin. Kyphoscoliosis of trunk was present. On assessment of higher cortical functions, he had global developmental delay. He is not able to stand till date. He is able to speak only monosyllables and obeys simple commands. Central nervous system motor examination showed spasticity, reduced power (3/5 in lower limbs and 4/5 in upper limbs), exaggerated deep tendon reflexes of all four limbs, and bilateral plantar extensor. Cranial nerve examination was normal. There was no sensory deficit or cerebellar signs. Eye examination revealed ectropion, mildly congested conjunctiva, and small opacity in the cornea at 8 o’clock position. Fundus examination revealed glistening spots in the foveal and parafoveal region. The triad of congenital ichthyosis, mental retardation and spastic diplegia arouses the suspicion of SLS.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What was the age of the patient at the time of presentation?"], "ground_truth_arguments": ["6 - year - old"]}
{"id": "CaseReportBench:train-101", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case Report': 'A 29-year-old male patient presented with a 6-year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk. He complained of skin tightness around the abdomen while walking. He wandered to and fro between different specialists but without much help. He was diagnosed as Type 1 diabetic 6 years back and was receiving insulin since then. Cutaneous examination revealed large ill-defined hyperpigmented indurated plaques extending symmetrically from mid-truncal area to both thighs characteristically sparing the knees and medial aspect of buttocks. A prominent constriction band was noted around the abdomen. The lesions over thighs were associated with hypertrichosis and were warm to touch. Examination also revealed short stature (145 cm), hypospadias, micropenis, scrotal swelling, and mild hepatomegaly and inguinal lymphadenopathy. Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal. Nails and teeth were normal. Ophthalmologic and auditory examinations were normal. On the basis of cutaneous findings, we kept differential diagnosis of morphea profunda, pseudoscleroderma, POEMS syndrome, Rosai–Dorfman syndrome, pigmented hypertrichotic dermatosis, and scleredema as the possibilities. A deep skin biopsy was done from the indurated plaque on the lateral part of the left thigh and sent for histopathology. Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes. Routine laboratory investigations revealed a fasting blood glucose level of 250 mg/dL and random blood sugar of 338 mg/dL with glycated hemoglobin 10.2%. Thyroid profile, liver function, kidney function, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibody was negative. Ultrasound abdomen revealed mild hepatosplenomegaly and abdominal lymphadenopathy. Color Doppler study of the scrotal region revealed small penis, normal echotexture, no calcific plaques, and small left testis. Chest radiography and nerve conduction studies were normal. Computed tomography (CT) demonstrated marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees. Para-aortic and inguinal lymphadenopathy and mild pericardial effusion were noted. Marked thickening of the scrotum was seen. A diagnosis of “H syndrome” was made. Genetic testing was not possible due to resource constraints.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.'}", "questions": ["What congenital genital anomalies were identified on physical examination?", "What findings were reported on scrotal ultrasound of the genital region?", "What scrotal abnormalities were described on computed tomography?"], "ground_truth_arguments": ["hypospadias, micropenis, scrotal swelling", "small penis, normal echotexture, no calcific plaques, and small left testis", "Marked thickening of the scrotum was seen"]}
{"id": "CaseReportBench:train-235", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}", "questions": ["What inherited metabolic disorder was diagnosed in the patient?", "In the case report, an abbreviation CGL is mentioned. What is the relevance of this abbreviation to the patient's condition?"], "ground_truth_arguments": ["CGL", "She was therefore diagnosed with CGL ( Berardinelli - Seip syndrome ) ."]}
{"id": "CaseReportBench:train-560", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to house soiling and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. The environment consisted of two young adult humans with no children. They lived in a flat of 85 m 2, with two terraces of 5 m 2 each. There were three separated litter boxes at home, all of which were non-covered with low sides. The owners had used clumping, non-clumping, silica-based and soil-based litter during the months between the adoption (when the cat was 4 months old) and the first visit. One of the latrines always had clumping substrate. There were three food and three water troughs, all of them far from the latrines. The impression of the owners was that the cat eliminated where it was at any given moment. It eliminated many more times in front of the owner (90%) than when it was alone (10%). The cat never tried to cover its faeces or urine after depositions. Occasionally, the owners punished the cat verbally and physically, but only when it eliminated in front of them. The substrates used by the cat were ceramic tiles, the sofa and beds. It always adopted an emptying-body posture. Spots were always located on horizontal surfaces. The owners used bleach-based products in order to clean the spots, and just water in the case of the sofa and beds. Regarding the play-related problem, the owners said that the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘tried to bite, catch and scratch the air’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat’s behavioural history was unremarkable. The differential diagnoses of the house-soiling problem included problems with the litter trays, including insufficient number, incorrect type, competition with other cats for the latrines, incorrect location, acquired aversion, or inappropriate substrate; a preference for another location or substrate; a problem with preference acquisition (ie, because of a cognitive impairment, or a sensory impairment or an unavailability of appropriate latrines or substrate during the first few weeks of life); and marking behaviours. Finally, a medical illness can contribute to all of these problems or to be the main cause. 1, 2 We could rule out most of these problems after interviewing the owners. Firstly, it was unlikely that there was a problem with the litter tray because the number, type and location were correct. The locations were correct because the animal eliminated near the litter tray if it was there. Many different substrates had been used. Secondly, it was not a problem of preference because the cat eliminated in different locations and surfaces. The age of the animal, the distribution of the spots and the body posture during elimination ruled out marking behaviours. Alterations in play behaviours described by the owners could have been due to a cognitive impairment, and/or a sensory impairment (ie, blindness). Play behaviours depend on learning capability and sensory systems. 3 Additionally, an enriched environment is necessary to learn and display play behaviours in a proper manner. 4 In that case, the social and instrumental environment was good. Regarding elimination, a problem of substrate preferences acquisition was diagnosed. A cognitive impairment, a medical condition or both could have been the cause of the problem during the elimination habits acquisition. Moreover, cognitive impairment and some medical conditions also could explain the play-related behavioural problems. During the consultation, the physical examination was unremarkable; however, the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. A complete ophthalmological examination was performed by the ophthalmological service in order to rule out ocular diseases. No ophthalmological abnormalities were detected. Additionally, based on the behaviours at home described by the owners (the inability to find some toys, and the behaviour of ‘scratching and biting the air’), some degree of visual impairment was suspected but not confirmed with the neurological examination. The cat did not crash with objects either at home or at the consultation room. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits. The feline immunodeficiency virus/feline leukaemia virus test was negative. A thorax radiograph, abdominal ultrasound, brain magnetic resonance imaging (MRI; 0.2 T) and cerebrospinal fluid analysis showed no abnormalities. Although some small lesions could be missed with low-field MRI, we had to assume the absence of lesions obtained in the work-up. Thus, a degenerative condition such as a lysosomal storage disease, organic aciduria or mitochondrial encephalopathy was suspected. Samples of blood and urine were sent to the University of Pennsylvania School of Veterinary Medicine for metabolic screen tests. Amino acids, organic acids, carbohydrates, nitroprusside, ketone and mucopolysaccharide concentrations were analysed, as was α-mannosidase, β-mannosidase, fucosidase and hexosaminidase A and B activity. All of these were within normal limits. No treatment was prescribed for the neurological problem. The owners were given advice on correcting the soiling problem in the house using reward-based training with a clicker. During the first week, the clicker was conditioned by a food reward, and the entire floor was covered with newspaper. Each time that the cat eliminated, it was rewarded with a clicker and food. Newspaper was removed progressively. Three months later, the cat used a small newspaper-covered area to eliminate. This partial improvement suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability. After 3 months, the cat was referred to the neurology service again, in status epilepticus. Neurological findings, after the postictal phase, included a lack of bilateral menace response and cerebellar ataxic gait. A bilateral carpal valgus that had already been found in the first visit and a visible suture line in the posterior capsule of both crystalline lenses were also detected. The owners reported progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status (probably seizure activity). A symptomatic treatment with diazepam (1 mg/kg intrarectally only if seizures) and phenobarbital (2 mg/kg PO q24h) was started, with a very poor response. After 15 days of treatment, levetiracetam was added (10 mg/kg PO q8h) owing to an increase in seizure activity, with an initially good response. However, seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting <2 mins. After 2 years of treatment and a progressive worsening, the cat was euthanased. A complete necropsy was immediately performed. No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS. In order to rule out prion aetiology, a PrPsc inmunohistochemistry assay was performed, and the results were negative. Thus, congenital spongiform polioencephalomyelopathy (CSP) was diagnosed postmortem. Spongy vacuolation seen by light microscopy in the neural tissue is defined as spongy degeneration, and may take the form of vacuoles within processes of the neuropil, vesiculation of myelin sheaths, or swelling of astrocyte or oligodendrocyte cytoplasm. 5 A congenital problem, retrovirus infection and prion disease have been suggested as possible aetiologies. 6 – 10 Congenital spongiform degeneration of the grey matter has been previously described in a few cases of cats; 6 – 8 however, the cause remains still unknown. Common clinical signs include gait alteration, seizures, blindness, bilateral cataracts, behavioural changes and cranial nerve alterations. These signs appear during very early stages of development (just after birth), with a progressive fatal outcome in a few days or months. Behavioural signs are poorly described in animal science literature. 6 – 8 Although the degeneration usually affects diffusely all the grey matter, the behavioural alterations and the evolution of the clinical signs depend on the affected area of the brain in each case. Nevertheless, the clinical signs do not always correlate with the degree of the histological lesions. A spongy degenerative problem of grey matter has also been described in humans, and occurs in isolated cases and in sibs. 11 – 13 In all of human cases reported, the problem appears early in infancy and the outcome is always fatal. All the affected children show learning disabilities (ie, retarded speech development) during the early periods of infancy. Additionally, they rapidly develop neurological signs, especially seizures. The clinical findings and neuropathological changes are very similar in humans and the present case. There are no studies regarding degeneration of grey matter and its effect on learning ability in animals. However, other neurodegenerative problems (ie, lysosomal storage diseases) and problems that lead to structural abnormalities of the forebrain (ie, hydrocephaly) may be correlated with learning disabilities in animals and humans. 14 – 17 The acquisition of the elimination habits occurs during the first weeks of a kitten’s life. Most kittens naturally seek out sand-like materials for elimination purposes. However, the preference for a substrate needs to be learnt during those first weeks of age. Learning disabilities and/or sensory impairments could modify the acquisition of these habits.'}", "questions": ["What category of congenital spongiform disease was identified in the cat after necropsy?"], "ground_truth_arguments": ["congenital spongiform polioencephalomyelopathy ( CSP ) was diagnosed postmortem"]}
{"id": "CaseReportBench:train-20", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Radiological findings': 'Ultrasonographic examination revealed small hypoplastic uterus (6*7*3 ml) or atretic ovaries and adrenal glands had normal sizes. Clinical Course and Follow-up First, the patient hydrated with normal saline. Thereafter, considering hyponatremia, hyperkalemia, metabolic acidosis and decreased cortisol level and increased ACTH level, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) and sodium chloride was initiated. After replacement therapy, electrolyte abnormalities were corrected during first week and the patient was discharged from hospital with good clinical condition. She recommended referring for follow up. During follow-up, she had good clinical condition, with normal laboratory results except for 17 OHP which was lower during the period. At 6-years old, the patient referred with high blood pressure and adrenal insufficiency because of arbitrary drug discontinuation by mother. Renal Doppler ultrasonography and scan was performed which was normal. Regarding the recommendation of pediatric nephrologist fludrocortisone and sodium chloride was discontinued and treatment continued with hydrocortisone . Ultrasonography revealed the testicles in the abdominal cavity and uterus was not detected in pelvis. Orchiectomy was performed. Chromosome study showed 46XY pattern. On her most recent visit at the age of 6 years, the patient had no hyperpigmentation. Her height was 110 cm (10-25th percentile), weight 23 kg (75-90th percentile). Her last laboratory tests results were as follows; Na: 142 mmol/l, K: 4.5 mmol/l,17OHP: 0.1 ng/ml, ACTH: 22 pg/ml, Renin:50.8 pg/ml, Aldosterone: 105 pg/ml.', 'CASE REPORT': 'A 28-day-old phenotypic female infant was admitted to pediatric endocrinology clinic of Al-Zahra Hospital, affiliated to Isfahan University of Medical Sciences, because of poor weight gain and lethargy. She was a full-term infant with a birth weight of 3250 gr (50 th percentile), length of 51 cm (50 th percentile) and head circumference of 34 cm (50 th percentile).The patient had no perinatal problem. She was the 1 st child of nonconsanguineous parents. At the time of admission, she was lethargic without history of vomiting or diarrhea. There was not any familial history of similar presentation or features endocrine disease. She had no history of drug consumption except vitamin A+D.', 'Physical examination': 'She was lethargic, had depressed fontanele. She had mild dehydration and decreased skin turgor. In skin examination, she had mild hyperpigmentation, including oral cavity. External genitalia seemed normal female type with no ambiguity. There was not any abdominal or inguinal mass in abdominal examination. Her body weight, length and head circumference were 2900, 51 cm and 33.5 cm, all of them were beneath the 5 th percentiles. Her blood pressure was 60/40 mmHg, respiratory rate was 39/min, pulse rate was 112/min and body temperature was 37.1°C.'}", "questions": ["What hyperpigmentation findings were reported for the patient throughout the case report?", "What observations were noted regarding the patient's skin during the physical examination?"], "ground_truth_arguments": ["no hyperpigmentation", "decreased skin turgor.", "mild hyperpigmentation, including oral cavity."]}
{"id": "CaseReportBench:train-515", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case 5': 'A 62-year-old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5-year history of an asymptomatic eruption on the neck. Physical examination revealed numerous soft, oval-to-round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area. Echocardiography was unremarkable. The ophthalmologic examination was normal. Moreover, no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption.', 'Histopathology of cases (1–3)': 'A skin punch biopsy was performed, and the hematoxylin and eosin (H and E) sections revealed a normal-appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.', 'Histopathology of case 4 and 5': 'H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident.', 'Case 3': \"A 68-year-old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years. Physical examination revealed numerous tan to yellowish soft papules over the lateral side of the patient's neck, measuring 2–3 mm. The patient had no systemic symptoms and was otherwise healthy.\", 'Case 4': \"A 61-year-old female patient presented to the clinic with a 2-year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis. On physical examination, there were multiple symmetrically distributed, skin-colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient's neck, upper chest, and the antecubital fossa of both forearms. There was no history of sun exposure or family history of similar cutaneous manifestation.\", 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Case 2': \"A 77-year-old female presented with a 4-year history of gradual appearance of small skin-colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension. However, other systemic examinations were unremarkable, especially for eye, cardiac, or gastrointestinal systems.\", 'Case 1': 'A 71-year-old female presented with a 1–2-year history of asymptomatic skin-colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints. Given the clinical resemblance to PXE, an ophthalmology consult was performed to rule out the presence of angioid streaks. The eye examination was normal.'}", "questions": ["What are the patient’s age, gender, and any notable lifestyle factors (e.g., smoking history) mentioned?", "What pre‑existing medical conditions or comorbidities are reported for the patient?", "How long has the skin eruption been present and what symptoms (e.g., itching, pain) are associated with it?", "What triggers or exposures, if any, are linked to the onset or worsening of the lesions?", "What size range is given for the lesions?", "What colour(s) and morphological description (e.g., papules, plaques) are provided for the lesions?", "What anatomical region(s) are described as the primary or most emphasized sites of the lesions?", "Summarize the document’s statement about family history of similar skin conditions.", "Summarize the document’s statement about prior sun exposure before the eruption.", "What does the document say regarding the presence or absence of systemic symptoms or other organ‑system involvement?", "Are any abnormal examination findings or systemic abnormalities reported in relation to the skin condition?"], "ground_truth_arguments": ["A 62 - year - old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5 - year history of an asymptomatic eruption on the neck", "no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption", "A 68 - year - old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years", "The patient had no systemic symptoms and was otherwise healthy", "A 61 - year - old female patient presented to the clinic with a 2 - year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis", "There was no history of sun exposure or family history of similar cutaneous manifestation", "A 77 - year - old female presented with a 4 - year history of gradual appearance of small skin - colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient 's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension", "A 71 - year - old female presented with a 1–2 - year history of asymptomatic skin - colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints"]}
{"id": "CaseReportBench:train-607", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': 'SH is a 44-year-old female diagnosed with mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure. After her diagnosis was made, she was initially followed by Neurology; however she was subsequently referred to our cardiomyopathy clinic secondary to progressive left ventricular hypertrophy (LVH) on echocardiogram and the known association between MELAS and cardiac disease. Prior to evaluation by our clinic, she had a clinical diagnosis of MELAS but evaluation by our cardiovascular genetics team yielded positive results for the A-to-G transition at nucleotide 3243 (m.3243A > G) of the mitochondrial genome, with 25% heteroplasmic deleterious mutation in MT-TL1, a mitochondrial leucine transfer RNA gene, the most common mutation underlying MELAS. At the time of presentation to our clinic, SH had carried the diagnosis of MELAS for 11 years and her symptoms had progressed significantly so that she was no longer able to be employed and her husband became her primary caretaker. Her clinical status included multiple medical problems related to her MELAS diagnosis: sensorineural hearing loss, myopathy, bilateral ophthalmoplegia, ptosis, seizures and stroke-like episodes with concern for dementia. Her family history is significant for a 12-year-old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss. In addition to a clinical exam and genetic evaluation, cardiac work-up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non-sustained atrial tachycardia ( Fig. 1 ). From a cardiac imaging perspective, an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub-epicardium of approximately 25–50% in thickness in the inferior segment at the base, inferior to lateral segments at the mid-ventricle and lateral segment of the apex, with sparing of the endocardium and septum ( Fig. 1 A and 1 B). Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes (R > L), and moderate cerebellar atrophy with extensive white matter disease. Monitoring laboratory evaluation yielded no significant abnormalities with the exception of a slightly elevated brain natriuretic peptide of 305 (normal < 200 ng/L). Her liver and kidney functions were normal and there was no hyperglycemia. From a cardiac management perspective, she has been maintained on Atenolol 25 mg twice daily and aspirin 325 mg once daily.'}", "questions": ["At what point in the patient's life was MELAS diagnosed, and what type of event led to its identification?", "Which family members are known to have MELAS, and what general types of symptoms have been reported in them?"], "ground_truth_arguments": ["diagnosed with mitochondrial myopathy, encephalopathy and stroke - like episodes ( MELAS ) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure.", "Her family history is significant for a 12 - year - old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss"]}
{"id": "CaseReportBench:train-73", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': 'A 4-year-old female patient with a nasal anomaly was admitted to our outpatient clinic. She was born 2300 g prematurely on her 37 th gestational week from a 34-year-old mother with a history of five pregnancies, two still births and two abortions. On her physical examination, she had a left-sided supernumerary nostril and cliteromegaly. Her laboratory studies revealed low levels of androstenedione and her history showed that she had medical therapy for 1 year for her congenital adrenal hyperplasia. No additional anomaly except patent foramen ovale was detected in her work-ups. Paranasal sinus computed tomography study revealed that her left-sided accessory nostril opened to the left nasal cavity. The patient was operated, the opening of the supernumerary nostril to the nasal cavity was obliterated and the widened nostril was narrowed by excisions from the alar ground and lateral side. A revision toward the nostril asymmetry is planned 1 year after the operation.'}", "questions": ["What endocrine disorder was previously diagnosed in the patient and treated with one year of medical therapy?", "Which congenital adrenal condition is mentioned as part of the patient's medical history?", "What specific diagnosis related to adrenal hyperfunction is identified in the case report?"], "ground_truth_arguments": ["congenital adrenal hyperplasia"]}
{"id": "CaseReportBench:train-276", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Report': 'A 57-year-old woman presented with a history of multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs. The patient was referred from the neurology department for management of these painful masses, which were obstructing her ability to breath and sleep, forcing her to require home oxygen and a wheelchair for ambulation. She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back. Our patient reported a history of myoclonus epilepsy with ragged red fibers (MERRF) syndrome with symptoms including cardiomyopathy, peripheral neuropathy, ataxia, muscle weakness, and myoclonus. She reported multiple family members having MERRF syndrome including her mother, maternal grandmother, maternal great grandmother, sisters, brothers, her sons, and nephews with variable presentations and lipomas. Physical examination found the patient seated in a wheelchair on supplemental oxygen. Multiple symmetric large, variably sized tender masses were easily apparent and palpable around her neck, upper back, upper lateral arms, mid and lower back, lower abdomen, and upper thighs ( Fig 1, Fig 2, Fig 3 ). Fig 1 Frontal view. Patient with symmetric supraclavicular lipomatosis. Fig 2 Posterior neck. Upper back buffalo hump lipomatosis. Fig 3 Lateral view. Symmetric lipomatosis of upper arms.'}", "questions": ["What cardiac condition is mentioned in the patient's medical history?", "Which heart-related manifestation is associated with the patient's MERRF syndrome?"], "ground_truth_arguments": ["cardiomyopathy"]}
{"id": "CaseReportBench:train-357", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["What cardiac symptom or event did the patient experience at age 30?", "What abnormality was reported on the 24‑hour ECG performed when the patient was 30 years old?", "What structural finding was described on the transthoracic echocardiogram performed at age 40?", "How was heart failure addressed or described in the patient's clinical assessment?"], "ground_truth_arguments": ["syncope at age 30y", "24h - ECG at age 30y disclosed an intermittent AV - block II", "Transthoracic echocardiography at age 40y revealed mild myocardial thickening", "no indication for heart failure"]}
{"id": "CaseReportBench:train-2", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case Report': 'XY2 is a boy of seven years of age with X-linked hypophosphatemia. He inherited this genetic disorder from his mother, who in turn inherited it from her father. Mutations in the PHEX gene to Xp22.1 are responsible for the clinical impression of X-linked hypophosphatemia. A molecular analysis of the PHEX gene and sequence analysis showed a hemizygote 1735 G>A(G579R) missense mutation in exon 17 of the PHEX gene in all subjects. XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth. XY2 is intellectually gifted (WISC-III Full Scale IQ: 135, Verbal IQ: 136, Performance IQ: 133) Psychiatric examination demonstrated a DSM-IV-diagnosis of AD, confirmed by the ADI-R (autism diagnostic interview - revised) of the parents and the ADOS-G (autism diagnostic observation schedule). XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X-linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI-R was conducted with the parents and an ADOS-G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC-III test. XY1 is of normal intelligence (total IQ: 107, verbal IQ: 106, performance IQ: 107). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism'}", "questions": ["What growth-related problem is described for the patient with X-linked hypophosphatemia?"], "ground_truth_arguments": ["lack of growth."]}
{"id": "CaseReportBench:train-128", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case presentation': \"This is a 20-year-old female with a 6-month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days. Her vital signs on admission showed uncontrolled hypertension (BP = 148/118 mm Hg) and tachycardia (HR = 120 bpm). She was unable to eat during the last few days. On the second day of her admission, she had two generalized tonic–clonic seizures. She received lorazepam and levetiracetam, and her clinical seizures resolved; however, she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region. The patient was transferred to the ICU for blood pressure control and was started on treatment with acyclovir, antihypertensive medications, and antibiotics. She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid (CSF) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus . The brain MRI showed PRES ( Fig. 1 ). Because the stat EEG showed LPDs + F, a highly epileptogenic pattern, cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording. Therefore, clinical and electrographic seizures completely subsided with treatment. Acyclovir was discontinued, and high dose steroids were started, considering the possibility of immunological and inflammatory etiologies. The patient showed clinical improvement, but her abdominal pain persisted, and the diagnosis of an acute porphyria was suspected. Urine, then serum and fecal porphyrins were requested. The results were as follows: urine PBG level was 177.4 μmol/L (reference: 0 to 0.88 μmol/L), serum porphyrin level was 58 nmol/L (reference: 0 to 15 nmol/L), fecal coproporphyrin was 18 nmol/g (reference: 0 to 45 nmol/g), and fecal protoporphyrin was 10 nmol/g (reference: 0–100 nmol/g). Taken together, the highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels, were suggestive of AIP. The patient's abdominal pain resolved in less than 24 h with carbohydrate (glucose) loading and highly caloric diet. Therefore, intravenous hemin was not necessary at that time. She was discharged home in stable conditions and offered to follow up at a porphyria center of her choice for further confirmatory genetic testing, management, and counseling. The patient was seen in our epilepsy outpatient clinic one month later. She was not taking any medications. She was asymptomatic, and her neurological exam was normal. A follow-up brain MRI showed remarkable improvement.\"}", "questions": ["What was the patient's age group or range at the time of presentation/admission?"], "ground_truth_arguments": ["a 20 - year - old"]}
{"id": "CaseReportBench:train-618", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case': \"A 27-year-old female was admitted to the hospital because of left hemiplegia and aphasia. She was 162 centimeters tall and 30 kilograms in weight. She was born after a normal pregnancy and delivery. There was no family history of neurological diseases. Motor and intellectual development was normally attained during infancy. She was hospitalized for general muscle weakness and gait disturbance when she was 6 years old. A neurologic exam showed decreased muscle tone and strength, and atrophic muscle mass. She had consistent muscle weakness, so a muscle biopsy was performed from the calf muscle when she was 8 years old. The biopsy showed mitochondrial myopathy of the pleoconial type. Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems. Follow-up procedures were performed in an outpatient clinic once or twice a year. When she was 24 years old she had sudden syncope. An magnetic resonance imaging (MRI) revealed acute infarction of the left basal ganglia and the left frontal lobe. Two years later, when the patient was 26, she had another stroke and presented with general weakness, aphagia, and dysarthria. An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia. These clinical and radiological findings suggested brain involvement of MELAS syndrome. Thus, further evaluation was done for MELAS syndrome including blood lactate and genetic analysis. The plasma lactate level was 21.8 mg/dL (normal range 4.5-19.8 mg/dL). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng/dL (normal range 0.89-1.76 ng/dL) and TSH was 0.04 µIU/mL. Levels of complement component 3 and 4 were 13 mg/dL (normal range 75-145 mg/dL) and 18 mg/dL (normal range 12-72 mg/dL) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti-double stranded DNA was 1.6 (normal range 0-6). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation: m.3303C>T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome. She was treated with supportive care and rehabilitation for a month and was then discharged. Warfarin was used during the hospital stay, but was stopped when she was discharged, because MELAS syndrome causes nonvascular infarct and there is no report about the related risk of thromboembolism. One year later, she presented with another stroke with associated left sided weakness, and was subsequently admitted to the hospital. Her vital signs were stable and there were no specific findings in chest X-rays or electrocardiography. Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25%. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 ). The patient's mental status and general condition improved after she was treated with mannitol and anticoagulation therapy. Rehabilitation and supportive care, including warfarin, were followed and maintained. The patient was discharged after a month.\"}", "questions": ["What age group does the patient belong to at presentation?"], "ground_truth_arguments": ["27 - year - old"]}
{"id": "CaseReportBench:train-611", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Chief complaints': 'A 52-year-old female presented with a sudden onset of right-sided numbness and weakness that was accompanied by a left temporal cluster-like headache. No fever or prodromal infection was found at disease onset.', 'Imaging examinations and history of present illness': 'MRI demonstrated a lamellar left parietal lobe lesion predominantly involving the cortex, with hyperintensity on both diffusion-weighted imaging and fluid-attenuated inversion recovery (Figure 1 ). The apparent diffusion coefficient map revealed a preserved, isointense signal. No abnormalities were found by susceptibility weighted imaging or magnetic resonance angiography and venography (Figure 1 ). Due to the stroke-like onset pattern and MRI features, further thrombophilia screening was performed and showed decreased protein S activity. A diagnosis of cortical venous thrombosis was first proposed. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) was also considered but temporarily excluded because of the incomplete manifestation and lack of genetic evidence. Anticoagulation therapy was initiated, and follow-up was performed to maintain the international normalized ratio (INR) within the target range. Two months later, the patient was readmitted for subacute cognitive impairment. She was unable to identify and communicate with family members; she also had difficulty understanding questions or instructions and instead responded by repeating the word \"nothing\". During hospitalization, a secondary generalized seizure occurred, initially with eyes gazing to the right and then convulsion developing, which lasted for approximately 10 s before self-alleviation. Neurological examination suggested transcortical sensory aphasia, with fully covered limb strength. Blood tests and CSF examination were normal; INR was 2.21. On repeated MRI, new lesions were identified in the left temporal lobe and were also detected 10 days later in the right temporal lobe on radiological follow-up (Figures 1 and 2 ). Although the MRI signal characteristics are consistent with the initial findings, the original lesion in the left parietal lobe had been alleviated, with cortical atrophy. We further conducted magnetic resonance spectroscopy (MRS), which revealed markedly elevated lactate (Lac) concentrations in the regions of interest in the left temporal lesion (Figure 1 ). Mitochondrial encephalopathy was diagnosed, and genetic testing using peripheral blood was performed. However, DNA testing for frequent MELAS and myoclonic epilepsy with ragged red fibers syndrome mutations were negative. Because of the lack of symptoms of muscle weakness or pain, the patient declined our suggestion of performing a muscle biopsy. Anticoagulation therapy was terminated, and levetiracetam (1000 mg/d) was administered. At 3 mo after her second admission, the patient was experiencing involuntary movement in her left limbs, with repetitive flexion/extension. An MRI scan showed a hyperintense signal abnormality in the right parietal lobe (Figure 2 ). Brachial biceps biopsy was performed. Histopathology revealed no abnormalities, and no necrotic or regenerating fibers were observed; ragged-red fibers and intense succinate dehydrogenase activity were not detected. Nonetheless, complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a heteroplasmy level of 69.6%, in the mitochondrial complex I subunit gene MT-ND3 . In contrast, this mutation was not found in her peripheral blood cells.', 'Personal and family history': 'The family and personal history was unremarkable.', 'Physical examination upon admission': 'On physical examination, the height and weight of the patient were 154 cm and 56 kg, respectively. Vital signs were normal, as were heart, lung and abdominal exami-nations. Neurological examination showed intact mental status, with normal speech and comprehension. Mild 4/5 right-sided hemiparesis was present with normal tone in both the arm and leg, though no other focal neurological deficits were found. After admission, she complained of discomfort and tingling in the right leg, after which a generalized tonic-clonic seizure for 3 min occurred before it was stopped by a bolus of intravenous diazepam.', 'CASE SUMMARY': 'We report a 52-year-old woman with recurrent stroke-like episodes carrying the m.10158T>C mutation in the MT-ND3 gene, which is also responsible for fatal infant-onset Leigh syndrome. Despite the common mutation, the present case featured a distinct clinical and neuroimaging manifestation from Leigh syndrome. This patient presented with sudden onset of right-sided hemiparesis and hemilateral sensory disturbance accompanied by a left temporal cluster-like headache and later developed epilepsy during hospitalization, with no other signs suggestive of myopathy, lactate acidosis, or other systemic symptoms. Brain magnetic resonance imaging revealed variable lesions involving multiple cortical and subcortical regions. Furthermore, a negative genetic test obtained from peripheral blood delayed the diagnosis of mitochondrial disease, which was eventually established through second-generation DNA sequencing using biopsied muscle.', 'Laboratory examinations': 'Laboratory tests, including D-dimer, lactic acid, and serum autoantibody levels, as well as thyroid function and tumor markers indicated no apparent abnormalities. Glucose tolerance and lactic acid movement tolerance tests were normal. A lumbar puncture was performed, and her open intracranial pressure was 180 mm H 2 O. Cerebrospinal fluid (CSF) testing showed that cell counts and protein, glucose, chloride, monoclonal antibody, adenosine deaminase, and lactate dehydrogenas levels were within normal ranges.'}", "questions": ["What intrinsic muscle symptoms (such as generalized muscle weakness, muscle pain, myalgia, cramps, or exercise intolerance) were reported by the patient during the illness?", "What clinical, laboratory, electrophysiological, or histopathological findings indicating a primary myopathic process were described as absent or normal (e.g., normal creatine kinase, unremarkable EMG, lack of ragged‑red fibers, no abnormal mitochondrial staining, negative muscle biopsy for myopathy)?"], "ground_truth_arguments": ["lack of symptoms of muscle weakness or pain", "no other signs suggestive of myopathy"]}
{"id": "CaseReportBench:train-198", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'A 24‐year‐old woman was admitted to our hospital with mildly impaired consciousness and myoclonus in the extremities. She had been diagnosed with MELAS at 21 years of age. Genetic testing revealed a 3271 T>C transition in the MT‐TL1 gene, clinically confirming the diagnosis of MELAS. After admission to hospital, neurological examination showed myoclonic movement in the extremities, mandible, and trunk. Muscle weakness was detected in the upper and lower limbs bilaterally. A laboratory examination showed increased serum pyruvic acid (2.1 mg/dL) and lactate (75 mg/dL). Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging (Fig. 1 ). Antiepileptic drugs levetiracetam, perampanel, lacosamide, and clobazam were initiated. L‐arginine, coenzyme Q10, and L‐carnitine aimed at supporting mitochondrial energy production were given simultaneously. As the impaired consciousness and myoclonus persisted for 2 weeks, we undertook brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex. Electroencephalography revealed high‐amplitude slow and spiked waves. We diagnosed the patient with non‐convulsive status epilepticus. To control the seizures, propofol was given at a dose of 2.7 mg/kg/h for 12 h and then increased to 5.4 mg/kg/h, with midazolam added at a dose of 2 mg/h. On day 5, the urine appeared brown and arterial blood gas revealed metabolic acidosis (pH 7.261, pCO 2 33.0 mmHg, HCO 3 - 14.4 mmol/L, and lactate 99 mg/dL). Creatinine kinase was elevated at 20,999 U/L. The patient was diagnosed with PRIS. She was transferred to the intensive care unit (ICU) on day 19 of hospitalization. On admission to the ICU, the vital signs were as follows: body temperature, 39°C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths/min; and SpO2, 99% (FiO 2 40%). Laboratory findings showed metabolic acidosis (lactic acid, 99 mg/dL; pyruvic acid, 0.92 mg/dL), creatinine kinase 29,560 U/L, and myoglobin 9,845 ng/mL. We treated her with interruption of propofol and continuous hemodiafiltration for metabolic acidosis. We continued coenzyme Q10, L‐carnitine, and L‐arginine for mitochondrial support for MELAS and antiepileptic drugs including levetiracetam, perampanel, lacosamide, and clobazam. After concurrent treatment of PRIS and MELAS, metabolic acidosis and creatinine kinase gradually decreased after reaching 59,000 IU/L on day 2 of ICU admission. Continuous hemodiafiltration was discontinued on day 11. Tracheostomy was carried out because i.v. midazolam treatment was prolonged to control the status epilepticus. Mechanical ventilation was discontinued on day 25 (Fig. 2 ). After rehabilitation, the patient was discharged on foot.', 'Case Presentation': 'A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus. To control the non‐convulsive status epilepticus, propofol was administered. Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated. The patient was diagnosed with PRIS. We treated her with interruption of propofol. She required mechanical ventilation for 25 days. After rehabilitation, she recovered and was discharged.'}", "questions": ["What neurological signs related to consciousness and myoclonus were observed on admission?", "How were the myoclonic movements distributed across the patient's body (e.g., extremities, mandible, trunk)?", "What abnormalities were reported on the initial T2‑weighted brain MRI (including location and tissue characteristics)?", "For how long did the impaired consciousness and myoclonus persist before repeat imaging was performed?", "What combined findings were described on the repeat brain MRI and arterial spin labeling study (including lesion location and blood‑flow changes)?", "What patterns were observed on the electroencephalogram during the episode?", "What clinical diagnosis was made based on the patient's symptoms and EEG results?"], "ground_truth_arguments": ["mildly impaired consciousness and myoclonus in the extremities", "myoclonic movement in the extremities, mandible, and trunk", "Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging", "impaired consciousness and myoclonus persisted for 2 weeks", "brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex.", "Electroencephalography revealed high‐amplitude slow and spiked waves", "non‐convulsive status epilepticus", "impaired consciousness and myoclonus", "non‐convulsive status epilepticus"]}
{"id": "CaseReportBench:train-77", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Observation': 'An 18-month-old boy born after an uncomplicated full-term pregnancy was hospitalized for psychomotor regression and drug-resistant myoclonic epilepsy. There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected. The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay. Physical examination revealed a macrocephaly of 51 cm with a dysmorphic syndrome consisting of a frontal bossing and a broadening of the nasal bridge. The neurological examination revealed an axial hypotonia with no further optical problems or responsiveness to light. Ophthalmologic examination showed a cherry-red spot without optic atrophy. Cerebral computed tomography (CT) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter (Fig. 1 ). With magnetic resonance imaging (MRI) the thalamus was hyperintense on T1-weighted images and hypointense on T2-weighted images (Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem. Clinical data and thalamic involvement suggest metabolic diseases such GM2 gangliosidosis (e.g. Tay-Sachs and Sandhoff diseases) or GM1 gangliosidosis (e.g. Landing disease), Canavan disease or Alexander disease. Chromatography of amino acids in the blood, urine and cerebrospinal fluid (CSF) was normal and chromatography of organic acids in the urine was also normal. Enzymatic assays were performed in France and revealed a deficiency of both hexosaminidases A and B confirming the diagnosis of Sandhoff disease.'}", "questions": ["What neuroimaging findings are reported in the document, including CT and MRI observations of the thalamus, white matter, and any other brain structures that were noted as normal?"], "ground_truth_arguments": ["Cerebral computed tomography ( CT ) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter ( Fig. 1 ). With magnetic resonance imaging ( MRI ) the thalamus was hyperintense on T1 - weighted images and hypointense on T2 - weighted images ( Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem"]}
{"id": "CaseReportBench:train-187", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': \"A 21-year-old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009. Emergent colonoscopy was performed with the findings of (1) a large amount of blood in the rectum and sigmoid colon and (2) oozing from eroded rectal mucosa. Laboratory investigation revealed thrombocytopenia (platelets 10.3 × 10 4 / μl). Although the hemorrhage stopped spontaneously and did not occur again, the patient was referred to our hospital for further examinations. He had had no previous significant rectal bleeding. His past medical history was unremarkable except for occasional nasal bleeding during childhood. On physical examination, the abdomen was soft and flat; a non-tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin. Neurologic examination revealed no evidence of abnormalities. The laboratory data are summarized in table 1 . There were thrombocytopenia and slight leukocytopenia (platelets 6.7 × 10 4 /μl, white blood cells 3,180/μl). Other laboratory findings disclosed: total bilirubin 1.4 mg/dl (reference range 0.2–1.3), direct bilirubin 0.5 mg/dl (reference range 0–0.3), and prothrombin time activity 77.0% (reference range 90–130). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein-Barr virus and Helicobacter pylori ; however, there were no remarkable findings. Anti-DNA antibody test showed a titer of 1:40 (reference range <1:40). His platelet-associated immunoglobulin G (PAIgG) level was elevated to 166 ng/10 7 cells (reference range 9.0–25.0), however anti-platelet antibody (anti-platelet-binding IgG) was negative. Enhanced computed tomography (CT) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed (fig. 1a ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson's capsule (fig. 2 ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin-converting enzyme (ACE) concentrations (table 1 ), which is compatible with Gaucher disease. The enzymatic activity of leukocyte β-glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol/h/mg (reference range 56.76–74.85). We analyzed the seven common mutations (N370S, 84GG, F213I, IVS2+1, L444P, R463C and D409H) in the GBA gene as previously reported with the informed consent of the patient and found the compound heterozygous mutations L444P/D409H. Based on these results, we diagnosed the patient with Gaucher disease type 1. We started enzyme replacement therapy (ERT). 60 U/kg body weight imiglucerase, a macrophage-targeted recombinant human glucocerebrosidase, was injected every 2 weeks. Figure 1b shows the CT scan 5 months after ERT started. The liver and the spleen were sized down (liver: from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen: from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease, were also improved from 7.4 to 11.3 × 10 4 /μl and from 42.5 to 24.7 IU/μl, respectively (fig. 3 ).\"}", "questions": ["What were the patient's platelet count and white blood cell count at presentation?", "What were the total bilirubin, direct bilirubin, and prothrombin time activity values recorded initially?", "Which infectious serology tests were performed (HBV, HCV, EBV, H. pylori) and what were the results?", "What was the anti‑DNA antibody titer, the platelet‑associated immunoglobulin G (PAIgG) level, and was an anti‑platelet‑binding IgG detected?", "What did the enhanced CT reveal about liver size, spleen size, and the morphology of the splenic and superior mesenteric veins?", "What histopathological findings were observed in the liver biopsy, including cell type and fibrosis pattern?", "Which blood biochemical markers (acid phosphatase and angiotensin‑converting enzyme) were elevated?", "What was the measured leukocyte β‑glucosidase activity and its reference range?", "Which GBA gene mutations were identified in the patient?", "After five months of enzyme replacement therapy, how did the liver and spleen dimensions change on CT?", "What were the changes in platelet count and ACE concentration following enzyme replacement therapy?"], "ground_truth_arguments": ["thrombocytopenia and slight leukocytopenia ( platelets 6.7 × 10 4 /μl, white blood cells 3,180 / μl ). Other laboratory findings disclosed : total bilirubin 1.4 mg / dl ( reference range 0.2–1.3 ), direct bilirubin 0.5 mg / dl ( reference range 0–0.3 ), and prothrombin time activity 77.0 % ( reference range 90–130 ). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein - Barr virus and Helicobacter pylori; however, there were no remarkable findings. Anti - DNA antibody test showed a titer of 1:40 ( reference range < 1:40 ). His platelet - associated immunoglobulin G ( PAIgG ) level was elevated to 166 ng/10 7 cells ( reference range 9.0–25.0 ), however anti - platelet antibody ( anti - platelet - binding IgG ) was negative. Enhanced computed tomography ( CT ) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed ( fig. 1a ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson 's capsule ( fig. 2 ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin - converting enzyme ( ACE ) concentrations ( table 1 ), which is compatible with Gaucher disease. The enzymatic activity of leukocyte β - glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol / h / mg ( reference range 56.76–74.85 ). We analyzed the seven common mutations ( N370S, 84GG, F213I, IVS2 + 1, L444P, R463C and D409H ) in the GBA gene as previously reported with the informed consent of the patient and found the compound heterozygous mutations L444P / D409H.", "Figure 1b shows the CT scan 5 months after ERT started. The liver and the spleen were sized down ( liver : from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen : from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm ). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease, were also improved from 7.4 to 11.3 × 10 4 /μl and from 42.5 to 24.7 IU / μl, respectively ( fig. 3 ). \" }"]}
{"id": "CaseReportBench:train-106", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What was the patient's age at the time of presentation?"], "ground_truth_arguments": ["20 - year - old"]}
{"id": "CaseReportBench:train-466", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["What is the patient's reported height or growth status?", "What arm or elbow deformities are described in the patient?"], "ground_truth_arguments": ["short stature", "cubitus valgus deformity"]}
{"id": "CaseReportBench:train-606", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': 'A 50-year-old male with a history of MERRF syndrome was found to have serum prostate specific antigen of 9.45 ng per milliliter on routine screening. His urological history was significant for mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35. There was no erectile dysfunction with a normal International Index of Erectile Function score (24/25). His urinalysis was negative for pyuria or microscopic hematuria. The patient had been diagnosed with a sporadic form of MERRF as an adult after developing symmetric lipomas in his cervical region along with exercise intolerance and mild muscle atrophy. Despite having the common MERRF mitochondrial DNA mutation (A8344G) in his blood with multiple symmetric lipomatosis, his variant of MERFF did not include cognitive impairment nor seizures. 1 His past medical history was significant for a history of hypertension and hypercholesterolemia and his medications included levocarnitine, losartan, hydrochlorothiazide, and metoprolol. His surgical history included a tonsillectomy as a child and plastic surgery to remove neck lipomas. His family history was positive for lung and liver cancer in his mother. His physical examination showed normal vital signs and a body-mass index of 25 (height: 1.65 m, weight: 68 kg). Relevant findings included large, painless, symmetrical cervical lipomas ( Fig. 1 A and B), normal external genitalia, and a digital rectal examination revealing a soft prostate with good lateral definition bilaterally and an estimated volume of 30 cubic centimeters (cc.). A neurological examination was normal except for mild muscle weakness at the end of the day. Fig. 1 (A) Front and (B) lateral images of the patient with MERRF syndrome with characteristic cervical lipomas (with patient permission). Fig. 1 The patient underwent a 12-core ultrasound-guided transrectal prostate biopsy revealing grade group 2 adenocarcinoma (Gleason score 3 + 4 = 7) at the left mid for 9 mm (mm.) and right base for 5.5 mm., and grade group 1 (Gleason score 3 + 3 = 6) at the left base for 9 mm. Perineural invasion was present. His transrectal prostate ultrasound showed a prostate volume of 28.9 cc but no hypoechoic nodules. His calculated PSA density was 0.32 ng/ml/cc. After discussing all the treatment options, the patient chose a radical prostatectomy given his young age, high PSA density, moderate voiding dysfunction, and grade group 2 with significant involvement (9 mm. 5.5 mm., 9 mm.). Since proceeding with surgery was contingent upon neurology clearance, the patient was evaluated by his neurologist with a specialty in mitochondrial disorders. Given that his MERRF variant was only associated with mild myopathy, the patient was cleared for surgery with a willingness to accept a potentially higher risk of complications during intubation given his neck lipomas, as well as a theoretically higher risk of urinary incontinence or erectile dysfunction given the associated myopathy which characterizes the MERRF syndrome. The patient underwent a transperitoneal bilateral nerve-sparing robotic radical prostatectomy and pelvic lymphadenectomy without complications. There were no intubation-related complications; operative time was 150 minutes with an estimated blood loss 50 cc. The patient was discharged on postoperative day 1 without complications nor transfusions and his catheter was removed on postoperative day 7. His prostatectomy pathology was grade group 2, pathologic stage T2 with negative margins and lymph nodes. Based on the EPIC short form questionnaire administered four months after surgery the patient was free of pads and his PSA was less than 0.1. ng/ml. After 6 months, the patient could achieve intercourse with the aid of vardenafil on-demand with an International Index of Erectile function of 20/25. At last follow-up 52 months after surgery, the patient continues to be continent, has satisfactory sexual function using daily tadalafil, and his PSA remains less than 0.1 ng/ml.'}", "questions": ["What are the patient’s demographic details (age, sex) and any diagnosed mitochondrial or genetic disorder?", "Describe the findings of the patient's prostate-specific antigen test and the context in which it was performed.", "Summarize the urinary symptoms reported by the patient and any scoring system used to evaluate them.", "Explain the patient's erectile function status and how it was assessed using a standardized index.", "Which chronic medical conditions (e.g., hypertension, hypercholesterolemia) are listed in the past medical history?", "What prior surgical procedures (performed before the current prostate cancer management) are mentioned in the patient’s history?", "What cancers are reported in the family history and which relative(s) are affected?"], "ground_truth_arguments": ["A 50 - year - old male with a history of MERRF syndrome was found to have serum prostate specific antigen of 9.45 ng per milliliter on routine screening. His urological history was significant for mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35. There was no erectile dysfunction with a normal International Index of Erectile Function score ( 24/25 ).", "past medical history was significant for a history of hypertension and hypercholesterolemia", "surgical history included a tonsillectomy as a child and plastic surgery to remove neck lipomas", "family history was positive for lung and liver cancer in his mother"]}
{"id": "CaseReportBench:train-541", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case report': 'Phenotypic female twins (A, B) were born at 36+2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g (<10 percentile) in A and 2,040 g (10 to 25 percentile) in B, height was 43 cm (10 to 25 percentile) in A and 44 cm (10 to 25 percentile) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit (NICU). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17-OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17-OHP, elevated ACTH (A, 4,379.2 pg/mL at 23 days of life; B, 11,616.1 pg/mL at 29 days of life), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng/mL/hr). However, the level of plasma cortisol before treatment were normal (8.71 µg/dL initially, 7.11 µg/dL in 2nd sample) in patient A, but low (1.5 µg/dL) in patient B. The results of endocrinologic investigation are shown in Table 1 . The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography (CT) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level (132 to 139 mmol/L) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia (129 to 133 mmo/L) and further evaluation for skin hyperpigmentation. She was treated with oral supplementation of sodium (0.8 to 0.9 mmol/kg) at 11 to 35 days of age, and she discharged from the hospital with normal sodium level after tapering off sodium supplementation at 37 days of age. Patient A was admitted at 38 days of age with adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration. Clinical findings of patient A were suggestive of CLAH and prompted us to order a gene analysis in both twins. Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C>T (p.R182C) in exon 5 and c.722C>T (p.Q258X) in exon 7 ( Fig. 1 ). Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms, except hyponatremia, but she was also diagnosed with CLAH with the same StAR gene mutation with patient A. The results of gene analysis of parents showed heterozygous for the mutations in the StAR gene; the heterozygous gene mutations; c.772C>T in the mother, and c.544C>T in the father, were documented. They showed suboptimal levels of hormone despite of administration of 20 mg/m 2 /24-hr of hydrocortisone, dose of hydrocortisone was increased up to 30 mg/m 2 /24-hr. Both patients have been under steroid supplementation (fludrocortisones 0.2 mg daily in 2 divided doses, and hydrocortisone 12 mg daily in 3 divided doses) at 14 months of age. They showed normal development except retarded physical growth, and hormones and electrolyte levels on follow up are shown as Table 1 . Body weight was 8.8 kg (3 to 10 percentile) in patient A, 9.4 kg (10 to 25 percentile) in patient B, body length was 73.7 cm (3 to 10 percentile) in patient A, 75.4 cm (10 to 25 percentile) in patient B at 14 months of age. They had been regularly followed.'}", "questions": ["How is the overall development of the twins described in the case report?"], "ground_truth_arguments": ["normal development"]}
{"id": "CaseReportBench:train-339", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["What age group does the patient fall into at presentation?"], "ground_truth_arguments": ["25 - year - old"]}
{"id": "CaseReportBench:train-601", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case': \"A 21-year-old woman was admitted to the hospital for a seizure-like episode lasting for approximately five minutes and subsiding spontaneously. The patient had frequent and insidious onset of seizure-like episodes, dysarthria, gait disturbance and a right-sided visual field defect that had started four years ago without any history of essential hypertension, diabetes mellitus and dyslipidemia. The patient initially presented with blood pressure of 111/59 mm Hg, pulse rate of 109 beats/min, respiratory rate of 20/min, and body temperature of 36.0℃. Laboratory results were raised cerebrospinal fluid (CSF) lactate of 5.2 mmol/L. Electroencephalography (EEG) showed diffuse cerebral dysfunction. Electromyography revealed sensorimotor polyneuropathy and chronic myopathy. Brain MRI showed infarction in the right temporal lobe, ischemia in the left posterior frontoparietal cortex and basal ganglia, and cystic lesion in the pineal gland with brainstem and cerebellar atrophy ( Fig. 1 ). Biopsy of left vastus lateralis showed neurogenic atrophy and slightly increased lipid vacuoles without paracrystalline inclusion in the mitochondria ( Fig. 2 ). Based on these clinical findings, the patient was diagnosed with MELAS syndrome. Ten years later, she went to a dentist for treatment of dental caries. Five minutes after local anesthesia with lidocaine, her consciousness changed suddenly and she was urgently transferred to the emergency room of our institution. On arrival, she was stuporous with blood pressure of 209/147 mm Hg, pulse rate of 140 beats/min, respiratory rate of 25/min, and body temperature of 36.5℃. At that time, her electrocardiography (ECG) showed supraventricular tachycardia. After intravenous injections of 300 mg amiodarone, she recovered consciousness, and follow-up ECG showed sinus rhythm with pre-excitation ( Fig. 3 ). Transthoracic echocardiography revealed decreased early diastolic mitral annulus velocity (E' velocity) and abnormal myocardial texture which were possibly associated with the initial phase of restrictive cardiomyopathy. Considering her bedridden status due to underlying MELAS syndrome, medical treatment with propafenone was started. The patient was discharged and has been followed up without tachycardia attack.\"}", "questions": ["Describe the nature of the patient's episodic neurological events, including any associated motor or visual symptoms, and indicate the approximate time course of these events.", "List any prior diagnoses of essential hypertension, diabetes mellitus, or dyslipidemia in the patient's medical history."], "ground_truth_arguments": ["frequent and insidious onset of seizure - like episodes, dysarthria, gait disturbance and a right - sided visual field defect that had started four years ago without any history of essential hypertension, diabetes mellitus and dyslipidemia."]}
{"id": "CaseReportBench:train-550", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case 2': 'This patient too showed considerable hyperkeratosis of palms and soles. Intraoral examination showed more teeth present. Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds. All teeth had deep periodontal pockets and grade II mobility. Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits. On the basis of history, clinical and radiographical features a diagnosis of Papillon-Lefevre syndrome was made.', 'CASE REPORT': 'An 18-year-old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi-Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16-year-old brother also complained of similar problems. Systemic history-both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2-3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.', 'Case 1': 'Patient showed bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees. Intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility. Orthopantomograph showed severe horizontal bone loss..'}", "questions": ["What types of laboratory tests were obtained for the patients to assess blood and metabolic parameters?", "Were any gum-related symptoms observed in the patients?"], "ground_truth_arguments": ["Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits", "bleeding gums."]}
{"id": "CaseReportBench:train-143", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What was the gestational term at birth and the birth weight of the patient?"], "ground_truth_arguments": ["He was born at term, weighing 2,900 g,"]}
{"id": "CaseReportBench:train-218", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Chief complaints': 'A 33-year-old woman was admitted to the psychiatric acute ward with the following symptoms: delusions of persecution, auditory hallucination, impulsive behavior, and emotional instability.', 'Personal and family history': 'There was no family history of psychiatric diseases.', 'CASE SUMMARY': 'A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported. The patient presented with cholestasis, cataract, Achilles tendon xanthoma, and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood. After the characteristic CTX findings on imaging were obtained, a pathological examination of the Achilles tendon xanthoma was refined. Re-placement therapy was then initiated after the diagnosis was clarified by genetic analysis. During hospitalization in the psychiatric ward, the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis. After the patient’s history of CTX was identified, the patient was diagnosed with organic schizophrenia-like disorder, and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication.', 'Physical examination': 'During hospitalization in the psychiatric ward, the patient’s brief psychiatric rating sale (BPRS) score was 40, her Wechsler intelligence scale score was 65, and the total biliary acid returned to normal levels. Nervous system examination showed normal muscle tone in the extremities, grade 5 muscle strength, instability in the heel-knee-tibia test of the right lower extremity, and a positive Romberg sign. In the mental status examination, the patient exhibited the following: verbal auditory hallucination; delusions of persecution; negative perceptions; irritability; childish emotions; poor general knowledge, understanding, judgment, and calculation; impulsivity; and lack of insight.', 'Imaging examinations': 'Brain magnetic resonance imaging (MRI) revealed symmetrical patchy abnormal signals in the dentate nuclei and deep medulla of the bilateral cerebellar hemispheres. These signals exhibited a slight decrease in signal intensity on T1-weighted images (T1WI) (Figure 2A ) and a slight increase in signal intensity on fluid attenuated inversion recovery (FLAIR) (Figure 2B ). Left-ankle-joint MRI showed that the inhomogeneous area had a considerable local thickening of the left Achilles tendon. The area displayed clear boundaries measuring approximately 6.6 cm × 1.2 cm and exhibited a slightly elevated signal intensity on T1WI and a similar slightly elevated signal intensity on the proton density weighted image, accompanied by linear hypointensity within (Figure 1B ). Brain magnetic resonance spectroscopy (MRS) showed decreases in N-acetylaspartate (NAA) intensities and increases in lactate and lipid signals (Figure 2C and D ).', 'Laboratory examinations': 'After nearly 3 years of adequate chenodeoxycholic acid treatment, the total biliary acid level returned to normal.', 'History of present illness': \"For 6 mo, the patient showed hostility towards her colleagues, firmly believing that they wanted to harm her. She could hear abusive voices of colleagues when she was alone. The false belief and voice interfered with the social relations and behavior of the patient, leading to outrunning behavior. In addition, the patient exhibited impulsive acts and temperamental behavior, such as tearing people's clothes, smashing things, standing outside naked when she became excited, and running around at midnight. She also experienced severe depression for several days, with crying and expressing a desire to commit suicide by euthanasia.\", 'History of past illness': 'According to her mother, the patient has been weak and obtuse since childhood and was unable to pass primary school exams. She required supervision and care from her family in her personal life. Despite being able to work, she could not perform her job well and did not get along with her colleagues, leading to her dismissal from several companies. At age 18, she underwent cataract surgery, and at age 26, she underwent cholecystectomy for cholestasis. A review of the patient’s medical records revealed that she presented with swelling in her left Achilles tendon, pain, and skewed walking to the right side 5 years ago. Three years ago, she was admitted to the neurology department, where biochemical tests revealed an elevated total biliary acid level of 11.2 µmol/L (normal value ≤ 10.0) and decreased levels of chenodeoxycholic acid and ursodeoxycholic acid. Subsequently, a biopsy of the left Achilles tendon was performed, revealing numerous lipid crystals and a few foamy macrophages (Figure 1A ). The patient underwent genetic analysis, which identified two mutations in the CYP27A1 gene associated with CTX: c.1263 + 3G>C and c.379C>T. On the basis of these findings, the patient was ultimately diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/d) and rosuvastatin (10 mg/d).'}", "questions": ["What psychiatric symptoms (e.g., delusions, hallucinations, impulsivity, emotional instability) prompted the patient's admission to the acute psychiatric ward?", "Which cerebellar signs were observed in adulthood and what intellectual or learning difficulties were reported from childhood?", "What psychiatric diagnosis was assigned to the patient?", "What were the patient’s Brief Psychiatric Rating Scale (BPRS) score and Wechsler intelligence scale score during hospitalization?", "What findings were noted on the nervous system examination (muscle tone, strength, heel‑knee‑tibia test, Romberg sign) and on the mental status examination (hallucinations, delusions, irritability, emotional tone, cognitive abilities, impulsivity, insight)?", "Describe the patient’s behavior, mood changes, and any depressive or suicidal thoughts over the past six months, including specific impulsive or temperamental actions.", "According to the patient’s mother, what were the early‑life characteristics regarding strength, cognition, school performance, need for supervision, and work functioning?", "What gait abnormality did the patient develop five years ago?"], "ground_truth_arguments": ["was admitted to the psychiatric acute ward with the following symptoms : delusions of persecution, auditory hallucination, impulsive behavior, and emotional instability. ',", "admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported.", "cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood.", "the patient was diagnosed with organic schizophrenia - like disorder", "During hospitalization in the psychiatric ward, the patient ’s brief psychiatric rating sale ( BPRS ) score was 40, her Wechsler intelligence scale score was 65", "Nervous system examination showed normal muscle tone in the extremities, grade 5 muscle strength, instability in the heel - knee - tibia test of the right lower extremity, and a positive Romberg sign. In the mental status examination, the patient exhibited the following : verbal auditory hallucination; delusions of persecution; negative perceptions; irritability; childish emotions; poor general knowledge, understanding, judgment, and calculation; impulsivity; and lack of insight", "For 6 mo, the patient showed hostility towards her colleagues, firmly believing that they wanted to harm her. She could hear abusive voices of colleagues when she was alone. The false belief and voice interfered with the social relations and behavior of the patient, leading to outrunning behavior. In addition, the patient exhibited impulsive acts and temperamental behavior, such as tearing people 's clothes, smashing things, standing outside naked when she became excited, and running around at midnight. She also experienced severe depression for several days, with crying and expressing a desire to commit suicide by euthanasia. \"", "According to her mother, the patient has been weak and obtuse since childhood and was unable to pass primary school exams. She required supervision and care from her family in her personal life. Despite being able to work, she could not perform her job well and did not get along with her colleagues, leading to her dismissal from several companies.", "skewed walking to the right side 5 years ago"]}
{"id": "CaseReportBench:train-66", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'CASE REPORT': 'A 17-year-old Venezuelan male with a 5-year past medical history of bilateral ptosis came for his regular ophthalmic and general health checkup (Fig. 1 ). He had diplopia, decreased visual acuity and nyctalopia. He was diagnosed with diplopia by a general practitioner 5 years ago since then the patient has not seen any physician for any eye examination or general health checkup. His personal and family history was non-significant. On examination, he had a short stature one standard below the mean with a BMI within normal limits. Ophthalmologic examination revealed bilateral and partial external ophthalmoplegia with mild limitations in gaze in all directions; visual acuity was four bilaterally with evidence of hypermetric astigmatism. On funduscopic examination, bilateral atypical pigmentary retinopathy was seen (Fig. 2 ). The differential diagnosis included KSS, chronic progressive external ophthalmoplegia, MELAS syndrome, myasthenia gravis, Pearson syndrome and retinitis pigmentosa. MRI brain, echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal except for EKG, which unveiled complete right branch block, and a left anterior hemiblock (Fig. 3 ). The Holter monitor recorded supraventricular extrasystoles and a defect in ventricular repolarization. His CSF protein and lactate levels were elevated. A biopsy of the anterior right tibial muscle showed a higher concentration of mitochondria with notable abnormalities in size, form and disposition of mitochondrial crests (Fig. 4 ). The diagnosis of KSS was made from the following findings: onset of disease before 20 years of age with chronic external ophthalmoplegia, cardiac conduction defects, pigmentary retinopathy and muscle biopsy. Figure 1: Bilateral ptosis. Figure 2: ( a and b ) Funduscopic examination showing atypical pigmentary retinitis. Figure 3: Electrocardiogram revealing a complete right bundle branch block and a left anterior hemiblock. Figure 4: Electron microscopy of the skeletal muscle tissue revealing abnormal disposition of mitochondrial crests, higher concentration of mitochondria with notable abnormalities in size and shape.'}", "questions": ["Which diagnostic tests, including imaging and laboratory assessments, were reported as normal in the evaluation of the patient?", "What specific abnormalities were identified on the patient's electrocardiogram?", "What findings did Holter monitoring reveal?", "What overall cardiac conduction defects were noted in this case?"], "ground_truth_arguments": ["echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal", "EKG, which unveiled complete right branch block, and a left anterior hemiblock", "The Holter monitor recorded supraventricular extrasystoles and a defect in ventricular repolarization", "cardiac conduction defects", "Electrocardiogram revealing a complete right bundle branch block and a left anterior hemiblock"]}
{"id": "CaseReportBench:train-475", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Patient Consent': 'Patient consent was obtained.', 'Case Presentation': 'A 24-year-old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease (CKD) was referred for preconception counseling. Cystinosis was confirmed by an elevated leucocyte cystine level in infancy. Early diagnosis, made possible by cystinosis in an older sibling, and good treatment adherence contributed to delayed kidney disease progression. Electrolyte abnormalities secondary to Fanconi syndrome were treated with daily supplemental dosages of potassium 96 mmol, phosphate 25.2 mmol, and sodium bicarbonate 53.6 mmol. There were no overt extra-renal complications apart from mild photophobia. Her average prepregnancy urine protein-to-creatinine ratio was 132 mg/mmol, α1-microglobulin-to-creatinine ratio was 30.7 mg/mmol, and estimated glomerular filtration rate (eGFR) was 89 ml per minute per 1.73 m 2 . On confirmation of pregnancy, losartan and cysteamine were discontinued. Low-dose aspirin was initiated for the prevention of pre-eclampsia. As expected, proteinuria and eGFR increased during pregnancy. 8 Blood pressure remained normal with no evidence of gestational hypertension or pre-eclampsia. Daily electrolyte supplementation increased to potassium 128 mmol and phosphate 33.6 mmol, with no increase in the dose of sodium bicarbonate. Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein. The pregnancy was complicated by recurrent urinary tract infections (UTIs) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia. After treatment of the complicated UTI, prophylactic oral antibiotics were administered for the remainder of pregnancy without UTI recurrence. She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes. The infant was admitted to the neonatal intensive care unit for 23 days. Cysteamine was reinitiated immediately after delivery and enalapril was initiated at 2 weeks postpartum. The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1-microglobulin-to-creatinine ratio and eGFR were stable ( Figure 1 ). Figure 1 Urinary proteins and eGFR at baseline, during pregnancy and postpartum. eGFR, estimated glomerular filtration rate. While breastfeeding, her delayed-release cysteamine dosage was 675 mg twice daily (0.84 mg/m 2 /d) compared with her prepregnancy dosage of 825 mg twice daily (1.06 mg/m 2 /d). The cysteamine dosage was reduced during breastfeeding as a precaution because of the lack of lactation safety data. She exclusively breastfed for 4 months and discontinued at 5 months. The cysteamine dosage subsequently stabilized at 750 mg twice daily (0.95 mg/m 2 /d). Breastmilk samples were collected and analyzed ( Table 1 and Supplementary Methods ). The calculated relative infant dose was 0.4%. The predicted infant cysteamine dose over 24 hours was 0.52 mg. Infant cysteamine levels were not measured. The infant had normal growth and development at 18 months and a normal leucocyte cystine level. Table 1 Breastmilk cysteamine concentration relative to dose of delayed-release cysteamine bitartrate at steady state Time postdose (h) Breastmilk cysteamine concentration (mg/l) 0 0.12 2 0.76 4 1.87 6 0.51'}", "questions": ["What renal condition is reported for the patient, and how is its severity described?"], "ground_truth_arguments": ["with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease ( CKD )"]}
{"id": "CaseReportBench:train-272", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}", "questions": ["What cysteamine formulation (immediate‑release) and dosing have the twins been on since their diagnosis?", "What cysteamine delayed‑release regimen is currently prescribed for each twin?", "Which cysteamine eye‑drop preparation are the twins using, and what is its intended purpose?", "Provide details of the twins' kidney transplant history, including the timing of the transplant and the donor source."], "ground_truth_arguments": ["They were on cysteamine bitartrate ( cystagon - immediate release ) since diagnosis . Each was currently prescribed Procysbi ( cysteamine - delayed release ) 675 mg every 12 hours . In addition , each twin was prescribed cysteamine hydrochloride ( 0.44 % ) eye drops due to cystine crystal accumulation in the lens and cornea . Both twins were transplanted 6 years previously with kidneys from a single deceased donor source ."]}
{"id": "CaseReportBench:train-185", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': 'In 1989, a 21-year-old male experienced visual loss after diving from a diving board. Ocular examination was performed the same day, and revealed bilateral subretinal hemorrhages and angioid streaks. After clearing of the hemorrhages, more breaks of Bruch’s membrane were identified. The macula was not affected and vision returned to normal in both eyes. Twenty years later, in April 2009, he presented again because of recent visual loss in the left eye. Visual acuity (VA) was 20/25 in the right eye (RE) and 20/40 in the left eye (LE). Clinical examination, FA, and OCT revealed active choroidal neovascularisation nasal to the fovea with leakage and edema. One month after a first intravitreal injection of bevacizumab, the edema had resolved and vision improved. Close follow-up with consideration of additional anti-VEGF injections was adviced. Moreover, we observed in both eyes angioid streaks, peau d’orange and a few comet tails, and made a tentative diagnosis of PXE. We identified the sequellae of diving induced breaks of Bruchs’ membrane with linear vertical break formation, different from the irregular course and spiderweb configuration of the angioid streaks. During the following months a total of 8 injections of bevacizumab were administred on the LE and despite this treatment growth of the choroidal neovascularization (CNV) was observed with further deterioration of vision. In January 2010, active CNV was also identified in the right eye and treatment with bevacizumab intravitreal injections was initiated. At last examination, in April 2011, VA was 20/60 in the right eye and 20/250 in the left eye, with in the left eye a large subfoveal CNV expanding on both sides of the fovea, and in the RE a smaller and mildly active subfoveal CNV requiring further treatment (Figure 1 (Fig. 1), Figure 2 (Fig. 2), Figure 3 (Fig. 3), Figure 4 (Fig. 4), Figure 5 (Fig. 5), Figure 6 (Fig. 6), Figure 7 (Fig. 7), Figure 8 (Fig. 8), Figure 9 (Fig. 9), Figure 10 (Fig. 10) ). With the aim to confirm PXE, the patient was referred for dermatologic examination and biopsy. At age 43, there were no typical plucked-chicken appearance, no papules, macules or other skin lesions. Three biopsies from the flexural skin of the axilla and the neck did not reveal PXE related changes. Subsequently, to further exclude or confirm PXE, a blood sample for genetic analysis was taken. Analysis showed that our patient was homozygous for the R1141X-mutation in the ABCC6-gene. The diagnosis of PXE was withheld, discussed with the patient, and shared with his treating generalist to allow optimal further follow-up of the condition.'}", "questions": ["What age group does the patient belong to at the time of initial presentation?"], "ground_truth_arguments": ["21 - year - old"]}
{"id": "CaseReportBench:train-206", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': 'Patient 1 (UPN 1) is a male who was diagnosed with WAS at the age of 5 months. He presented with incidentally detected thrombocytopenia (23,000/µL) with skin eczema and severe, recurrent otitis media and diarrhea on admission. The second male patient (UPN 2) presented with neonatal thrombocytopenia at birth and received intermittent intravenous immunoglobulin (IVIG). Thereafter he experienced skin eczema and recurrent infections such as cellulitis and pneumonia, until he visited our hospital at 3 months old. Flow cytometric analysis of peripheral blood mononuclear cells (PBMC) for these 2 patients revealed a defect in WASP, leading to the diagnosis of WAS. Subsequently, the nonsense mutations, Arg211stop and Arg13stop, were confirmed by genomic analysis ( 17 ). Before transplantation, these patients were treated with monthly infusions of IVIG as well as supportive treatment but there was no clinical improvement. CBSCT was performed in a laminar air flow room with conventional supportive therapy. The pre-transplantation conditioning regimen for the 2 patients was 1 mg/kg of busulfan intravenously every 6 hr on days -9 through -6. This was followed by 50 mg/kg of intravenous cyclophosphamide on days -5 through -3 and 30 mg/kg of intravenous antithymocyte globulin (ATG) on days -3 through -1. Prophylaxis for acute graft versus host disease (GVHD) included continuous infusion of cyclosporine A beginning on day -1, targeting whole blood levels to be 200 to 400 ng/mL, and 1 mg/kg/dose of methylprednisone every 12 hr on days 5 through 19, and then a taper. The degree of human leukocyte antigen (HLA) match confirmed by high resolution DNA typing between the infused CB and the patients was 4/6 for UPN 1 and 5/6 for UPN 2. Infused cell doses of TNC and CD34+ cells for UPN1 and UPN2 were 6.24×10 7 /kg and 5.08×10 7 /kg for TNC, respectively, and 1.33×10 5 /kg and 4.8×10 5 /kg for CD34+ cells, respectively. T-, NK-, and B-cell enumeration and quantitative immunoglobulin studies (for immunoglobulin G, A, M, D, and E) were performed. Cytofluorographic analyses of lymphocyte subpopulations were performed with murine monoclonal antibodies conjugated to either fluorescein (FITC) or phycoerythrin (PE) and then analyzed by flow cytometry (FACScan; Becton Dickinson, San Jose, CA, U.S.A.). Heparinized venous blood samples from patients and family members were fractionated on a Ficoll-Hypaque gradient to isolate PBMCs. For mutational analysis, genomic DNA was extracted from the peripheral lymphocytes, and 12 WASP gene exons were amplified by polymerase chain reaction (PCR) followed by direct sequencing according to the protocol of Sasahara et al. ( 18 ). Hematopoietic reconstitution following CBSCT was uneventful, with an absolute neutrophil count (ANC) of more than 500/µL on days 31 and 13 and a platelet count of more than 20,000/µL on days 58 and 50, for UPN 1 and UPN 2, respectively. Molecular chimerism studies using the VNTR method showed a complete donor cell type for these patients (data not shown). Acute GVHD did not occur, even after the infusion of HLA 1 or 2 antigen mismatched CB. UPN 1 experienced 1 episode of sepsis with B. cepacia during the pre-engraftment period without any complications. UPN 2 experienced fever and respiratory distress with hypoxemia due to pulmonary edema as well as skin rashes on the trunk in the pre-engraftment period (from days 8 to days 10), which mimics engraftment syndrome. He recovered with oxygen supply via endotracheal tube and fluid restriction as well as methylprednisone therapy. Both patients were clinically well without eczematous skin and recurrent infections at 60 months (UPN 1) and 55 months (UPN 2) post CBSCT. Clinical data regarding CBSCT are shown in Table 1 . The elevated total eosinophil counts and serum IgE levels have been normalized since 7 months post-transplantation in both children ( Table 2 ). Other immunologic parameters including IgG, IgA, IgM, IgD and lymphocyte subsets are summarized at Table 2 . To determine whether the genotype was corrected by CBSCT, we analyzed the WASP gene sequence before and after CBSCT in UPN 1. UPN 1 had a single base substitution (C665T) in exon 7 that results in an amino acid change in codon 211 (Arg211stop) before CBSCT. Following CBSCT, UPN1 had a normal sequence at the mutation site in exon 7 of the WASP gene ( Fig. 1 ).'}", "questions": ["What gastrointestinal symptoms were reported in the patients' clinical presentation?"], "ground_truth_arguments": ["diarrhea"]}
{"id": "CaseReportBench:train-499", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case presentation': \"An 11-month-old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full-term by Cesarean section and was the second child of the nonconsanguineous parents. The patient's older sibling was phenotypically female, but died in infancy without a clear diagnosis. Although the karyotype was 46, XY, the patient was raised as female gender since she had female external genitalia. In addition, hyponatremia and an elevated adrenocorticotropic hormone (ACTH) level were detected by tests. The blood pressure at clinic was 80/50 mm Hg. Laboratory analysis revealed that the baby had a mildly elevated cholesterol level of 5.72 mmol/L (normal: 2.85–5.70 mmol/L), but a normal triglyceride level. Her plasma sodium level was 131.7 mmol/L (normal: 135–145 mmol/L) with potassium concentration of 6.61 mmol/L (normal: 3.5–5.5 mmol/L). ACTH was >1250 pg/mL (0–46 pg/mL) with a morning cortisol of 1.23 μg/dL (normal: 4–22 μg/dL). Baseline sex hormone tests revealed luteinizing hormone <0.10 U/L, follicle stimulating hormone 1.78 U/L, testosterone 2.50 ng/dL, progesterone 0.44 ng/dL, estradiol 22.99 pg/mL, and dehydroepiandrosterone (DHEA) sulfate <0.1 μg/dL. Adrenal computed tomography (CT) scan revealed enlarged adrenal glands. Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular-like tissues were detected in the bilateral inguinal regions (left: 0.6 × 0.4 cm; right: 0.7 × 0.4 cm) by ultrasonography. Plasma renin activity (PRA) was 0.11 ng/mL per h (normal: 0.93–6.56 ng/mL per h) with a normal aldosterone level of 8.84 ng/dL (normal: 6.5–29.6 ng/dL). Given ambiguous genitalia, karyotype of 46, XY and decreased DHEA and testosterone levels, the diagnosis of 21-hydroxylase deficiency and 11 beta hydroxylase deficiency were excluded. Lacking hypertension and hypopotassemia, the clinical presentation of salt loss and decreased progesterone also did not support the diagnosis of 17OHD. Without an elevated progesterone level, cytochrome PORD was less considered. The differential diagnosis included 3β-HSD deficiency and LCAH. After the informed consent form was signed by the families and approved by the Institutional Review Board of Peking Union Medical College Hospital, further genetic analysis with gene sequencing indicated it is not defective HSD3B2 (related to 3β-HSD deficiency). However, a homozygous variant c.707_708delins CTT (p.Lys236Thrfs∗47) was found on exon 6 of the STAR gene. A truncated disease-causing protein was predicted with MutationTaster software. The variant mutation was found to cause a frameshift at codon 236 with a stop at codon 282. Both parents were found to be heterozygous for the variant (c.707_708delins CTT, p.Lys236Thrfs∗47) at the same locus of the STAR gene without phenotypic consequences. To further evaluate the family pedigree for mutation carriers, the patient's paternal and maternal grandparents also took part in the gene sequencing. The patient's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes (such as mild amenorrhea in women) were recorded, and there were no abnormalities in physical and laboratory examinations. The results of the patient, her parents, and paternal grandfather and maternal grandmother are shown in Fig. 1 . The genogram of LCAH in this family is presented in Fig. 2 . The patient was prescribed hydrocortisone 10 to 12 mg/m 2 and 9α-fludrocortisone 100 μg/d. Gradually, her skin hyperpigmentation and vomiting disappeared, and she had normal growth and development without adrenal crisis attacks. Her hormone and electrolyte levels remained normal, except for a persistently elevated ACTH level throughout 2 years of follow-up. At follow-up for 2 years, the patient is now 104.5 cm tall and weighs 23.3 kg at the age of 4 years old. Her plasma sodium level is 138 mmol/L with a normal potassium concentration of 4.8 mmol/L. Her ACTH level is still elevated (1176 pg/mL). Her baseline sex hormone levels are testosterone <0.1 ng/dL and progesterone <0.08 ng/dL. The level of PRA (1.06 ng/mL per h) is within normal range.\", 'Patient concerns:': 'A case was reported that an 11-month-old Chinese girl who presented with a sex development disorder and hyponatremia. The clinical and genetic tests were carried out to confirm the diagnosis. The genogram of this case was also explored and analyzed. The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular-like tissue in the bilateral inguinal regions were detected with abdominal ultrasound. She was suspected of having LCAH, and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT (p.Lys236Thrfs∗47) on exon 6 of the STAR gene.'}", "questions": ["What were the key characteristics of the delivery, including timing and method?"], "ground_truth_arguments": ["was born at full - term by Cesarean section"]}
{"id": "CaseReportBench:train-155", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 3-year-old boy was admitted to our emergency department because of convulsions and unconsciousness. He had been diagnosed as 21-hydroxylase deficiency at birth. He had been taking oral steroid (hydrocortisone) replacement therapy since then. His parents had stopped steroid therapy without the knowledge of the physician 3 days before the symptoms started. They were admitted to our hospital 6 hours after the onset of the symptoms. He was in coma and had seizures on admission. Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg/dl and white blood cell (WBC) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies. Intravenous hydrocortisone treatment was initiated. Electroencephalography showed focal epileptic activity. Routine brain MRI was performed. Diffusion weighted images (DWI) and susceptibility weighted images (SWI) were also obtained in order to detect ischemia and hemorrhage. T2-weighted and fluid attenuated inversion recovery (FLAIR) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical-subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical-subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient (ADC) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto-occiptal cortical-subcortical regions due to hypoxia and hypoglisemia. We obtained follow-up brain MRI on fifth, twelfth, and twentieth days once the treatment has started. DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae.'}", "questions": ["What were the laboratory findings, including plasma glucose level, white blood cell count, electrolyte status, and results of infectious agent testing?", "What abnormalities were identified on the initial brain MRI, detailing the regions involved, signal changes on T2-weighted, FLAIR, DWI, ADC maps, and SWI, and any evidence of cerebral edema or hemorrhage?", "What findings were observed on the follow‑up MRI performed on day 20, including lesion resolution, ventricular dilatation, cortical atrophy, and diffusion characteristics in the occipital lobes?"], "ground_truth_arguments": ["Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg / dl and white blood cell ( WBC ) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies", "T2 - weighted and fluid attenuated inversion recovery ( FLAIR ) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical - subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical - subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient ( ADC ) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto - occiptal cortical - subcortical regions due to hypoxia and hypoglisemia", "DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes"]}
{"id": "CaseReportBench:train-165", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case presentation': \"We present the case of an unsplenectomized man suffering from heterozygous GD1 with mutations of c.1226A>G (N370S) and RecNci I (L444P, A456P, and V460V) in the GBA1 gene, who developed recurrent pulmonary aspergillosis caused by Aspergillus fumigatus and a mycobacterial infection caused by Mycobacterium avium. Despite long-lasting therapy of both aspergillosis (including antifungal drugs and surgery), and the mycobacterial infection (triple therapy with rifampicin, ethambutol, and clarithromycin), recurrent positivity for M. avium and A. fumigatus was detected. A 65-year-old man, originating from northern Greece but living in Sweden for over 30 years, had been referred to the Hematology Center Karolinska for a consultation concerning suspected Gaucher disease. His past medical history was significant for several co-morbidities ( Table I ). Because of splenomegaly (18 cm) and mild thrombocytopenia, a bone marrow (BM) examination was performed at the age of 51, disclosing the presence of foamy macrophages classified as Gaucher cells (GCs). However, further investigations aimed at the confirmation of GD diagnosis were not performed at that time. At the age of 54 years, he developed malaise and a chronic cough. He was a smoker for 25 years but quit at the age of 50. Radiological examination disclosed mild pulmonary fibrosis and aspergillosis in the right lung. The microbiological examination of secretions from a bronchoalveolar lavage (BAL) showed growth of Aspergillus fumigatus and mycobacteria other than tuberculosis (MOTT). Antifungal therapy with itraconazole (100 mg 2 × 2 p.o.) was administered for 6 weeks, but the MOTT infection was not treated. Of note, several weeks after therapy onset, the patient's clinical course was complicated by pulmonary bleeding (the coagulation work-up was normal apart from moderate thrombocytopenia). The fungal infection did not fully respond to therapy, and 2 years after diagnosis the patient underwent a partial resection of the right lung due to an aspergilloma ( Figure 1 ). After surgery, his general status improved rapidly. At age of 59, the patient developed shortness of breath and cough. Echocardiography showed septal left ventricular hypertrophy, normal systolic function of the left ventricle (EF of 50%–60%), signs of diastolic dysfunction, mild insufficiency of both aortic and pulmonary valves, and a slightly elevated pressure in the pulmonary artery (PA) of 42 mmHg. Repeated microbiological examination of the BAL secretions revealed a growth of Aspergillus fumigatus and Aspergillus nidulans, but was negative for MOTT. HIV serology was negative, excluding acquired immunodeficiency syndrome (AIDS). Voriconazole was administered for aspergillosis periodically for 2 years (at the age 61–62 years). Afterwards, the patient's symptoms regressed, and control spirometry showed only moderately decreased results (VC 3.72 L, 82%; FEV 1 3.04 L, 84%; FEV 1 /SVC 82%; FVC 3.72 L, 82%). Chest X-ray did not show any active pathological lesions. However, computed tomography imaging (CT) revealed pronounced fibrosis of lung parenchyma. At the time of hematologic consultation (at the age of 65), thrombocytopenia and hyperferritinemia were noted. The final diagnosis of GD1 was confirmed by the absence of glucocerebrosidase activity in peripheral blood leukocytes and an increased activity of plasma chitotriosidase. Further direct DNA sequencing of the GBA1 gene revealed heterozygous mutations in the GBA1 gene ( Table I ). The patient's status consisting of splenomegaly, thrombocytopenia, and an increased susceptibility to pulmonary infections, which was probably due to lung involvement in the course of GD, was assessed as an indication for commencing treatment of GD. The patient was started on miglustat, which was considered the first line of GD1 treatment at that time due to the worldwide supply shortage of Cerezyme® during 2009–2010 ( 9 ). He received the commercially available miglustat capsules at a dose of 100 mg three times a day orally. Interestingly, the patient experienced an unusually rapid improvement of the whole blood platelet count (PLT), which normalized already after 2 months of miglustat therapy. Unfortunately, the patient developed malaise, diarrhea, poor appetite, weight loss (10 kg, 16% of his baseline body weight), and mild tremor for which miglustat was deemed accountable. During this time, the patient also developed cough, and a microbiological examination of the BAL secretions revealed growth of Aspergillus fumigatus (sensitive to voriconazole) and Mycobacterium avium . Inflammatory activation was observed at that time as presented in Table I . The patient discontinued miglustat after 4 months of treatment due to the adverse events and the above-mentioned pulmonary infections. Voriconazole was administered, and after 10 days his cough decreased but, after some days, returned, alongside malaise and night sweats. CT of the chest disclosed a new infiltrate in the lower lobe of the right lung, despite antifungal therapy ( Figure 2 ). Treatment with rifampicin, ethambutol, and clarithromycin for Mycobacterium avium was initiated. After 4 months of therapy, the patient was stronger, his cough and night sweats were clearly reduced, and he had regained 10 kg of body weight. After the Cerezyme® supply shortage had ceased, the patient was offered to start ERT. Unfortunately, he strongly refused administration of ERT despite our recommendations. Now, almost 2.5 years after the initiation of the triple therapy, and with intermittent periods of negativity, the patient is recurrently positive for Mycobacterium avium in his sputum, despite 8 months of triple therapy administered during the preceding year. During the periods of deterioration in his general condition, he was also positive for Aspergillus fumigatus in sputum.\"}", "questions": ["Which therapy was initiated as first‑line treatment for Gaucher disease type 1 during the Cerezyme® supply shortage, and what dosage and administration schedule were used?", "Why was miglustat selected as the first‑line treatment for Gaucher disease type 1 at that time?", "After the Cerezyme® supply shortage ended, what treatment option was offered to the patient?"], "ground_truth_arguments": ["miglustat , which was considered the first line of GD1 treatment at that time due to the worldwide supply shortage of Cerezyme ® during 2009–2010 ( 9 ) . He received the commercially available miglustat capsules at a dose of 100 mg three times a day orally .", "After the Cerezyme ® supply shortage had ceased , the patient was offered to start ERT"]}
{"id": "CaseReportBench:train-404", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}", "questions": ["What did the recent testicular ultrasound reveal about TART volume and what did the initial semen analysis show regarding sperm presence?", "What general abnormalities were observed in the 0800 pre‑medication biochemical profile, and how does the A4/T ratio inform the likely source of testosterone?", "What overall changes were noted after treatment in the testicular ultrasound findings, semen analysis results, and the 0800 biochemical assessments?", "What genetic alterations were reported in the CYP21A2 gene for this patient?"], "ground_truth_arguments": ["A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.", "Biochemical evaluation at 0800 before medication showed 17 - hydroxyprogesterone 13,060 ng / dL ( reference : 13 to 120 ng / dL ), androstenedione ( A4 ) 1025 ng / dL ( reference : 26 to 125 ng / dL ), ACTH 866 pg / mL ( reference : 5 to 46 pg / mL ), plasma renin activity ( PRA ) 7.1 ng / mL / h ( reference : 0.6 to 4.3 ng / mL / h ), FSH 1.7 U / L ( reference : 1 to 11 U / L ), LH 1.3 U / L ( reference : 1 to 8 U / L ), and total testosterone ( T ) 473 ng/ dL ( reference : 240 to 950 ng / dL ). His A4 / T ratio of 2.2 ( > 0.5 ) with low LH and FSH was suggestive of a mostly adrenal origin of his T.", "Repeat ultrasound showed 91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % ). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17 - hydroxyprogesterone 66 ng / dL, A4 16 ng / dL, ACTH 13.5 pg / mL, PRA 11 ng / mL / h, FSH 5.4 U / L, LH 1 U / L, and T 287 ng / dL", "CYP21A2 genotyping was performed. Our patient had a 30 - kb deletion ( CH-1 chimera subtype ) in one allele and IVS2 - 13A / C > G ( In2 G ) mutation in the second allele"]}
{"id": "CaseReportBench:train-366", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}", "questions": ["What is the confirmed inborn error of metabolism diagnosed in the patient?", "Which specific type of porphyria is identified as the underlying disorder?", "What primary metabolic disease is responsible for the patient's clinical presentation?", "What diagnosis is supported by the elevated porphyrin derivatives and porphobilinogen levels?", "What acute hepatic porphyria does the case report describe?"], "ground_truth_arguments": ["AIP"]}
{"id": "CaseReportBench:train-270", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case 2': \"A 13-year-old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks. On examination, there were severe atrophic scars on the face and exposed parts of the extremities, which had resulted in mutilating deformities of the fingers. Hypertrichosis, pigmentation, and milia formation were also present on the face. Though erythrodontia was not spotted with the naked eyes, the teeth revealed a pink-red fluorescence under Wood's lamp. Histopathological examination of an intact bulla revealed the subepidermal location of the blister. A clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity, blistering, and hypertrichosis. The early onset and the mutilation of the fingers were highly suggestive of CEP. The patient was investigated. Routine investigations, including liver and renal function tests, were within normal limits except for mild anemia (Hb 8.0 g/dl, reticulocyte count 7% of circulating erythrocytes). ELISA for HIV was negative. PBG was normal in urine. On screening with a spectrophotometer, urinary total porphyrin was 1187 nmol/mmol of creatinine (normal <35 nmol/mmol). Twenty-four-hour urinary levels of uroporphyrin and coproporphyrin were raised. The erythrocytic porphyrins showed a level of 124.3 μg/100 ml (reference value less than 40 μg/100 ml using the hematofluorometric method). A diagnosis of CEP was made.\", 'Case 1': \"A 3-year-old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks. On examination, the child's face was badly scarred. There was hypertrichosis on the shoulders, arms, and face. The teeth were of coppery-red color. There were a few intact blisters and crusted lesions on the hands and feet. Atrophic scars were also present on the extremities. On the basis of the history of blistering on the exposed areas since early infancy, healing with atrophic scarring, erythrodontia, and red-colored urine, we made a clinical diagnosis of CEP. Routine investigations were within normal limits except for mild anemia. The urine did not show increased level of porphobilinogen (PBG). Further investigations were not carried out. The child was treated symptomatically.\"}", "questions": ["What age range is commonly reported for the initial appearance of blisters in pediatric patients similar to the 13‑year‑old case?", "At what age do children typically first develop blisters on exposed areas, as seen in early‑onset cases?"], "ground_truth_arguments": ["4–5 years", "around 6 months"]}
{"id": "CaseReportBench:train-17", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}", "questions": ["What anthropometric measurements are reported for the patient?"], "ground_truth_arguments": ["Her height was 154 cm, weight 48 kg"]}
{"id": "CaseReportBench:train-365", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}", "questions": ["What was the confirmed diagnosis, and what potential underlying condition was suggested?"], "ground_truth_arguments": ["confirmed the diagnosis of neonatal hemochromatosis ( NH ; likely due to gestational alloimmune liver disease , GALD ) ."]}
{"id": "CaseReportBench:train-551", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 63-year-old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A-C ) was referred to our hospital due to an abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm ( Fig. 1D ). He had a history of hypertension for 5 years and a smoking habit (10 cigarettes/day). Coronary angiography revealed mild to moderate coronary atherosclerotic lesions ( Fig. 1E and F ). He was initially suspected of having FH based on his physical findings as well as the presence of AAA with a modestly elevated LDL cholesterol level (166 mg/dL). He was born to consanguineous parents (second cousins). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis. Recessive inherited disease was speculated at this point, so we investigated his genetic background using whole-exome sequencing, assuming a recessive form of inheritance. The mean depth was 99.9× per base across the whole exome. The percentage of on-target reads was 84.6%. Also, the coverage rate of target coding lesions (10×) was 99.0%. Bioinformatics analyses and segregation pattern matching followed by exome sequencing were performed for the patient to identify causative variants. The number of aligned variants in the patient that passed the standard quality control was 142,508. Of those, 15,335 were missense, nonsense, splice site, and frameshift variants. After removing “common” variants ( 10 ), 3,042 variants were detected. Subsequently, filtering against the segregation pattern assuming the recessive form of inheritance with the use of an in silico annotation prediction tool (scaled C-score >20) reduced the candidate variants to homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene (c.410G>A or p.Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ). Accordingly, an increased serum level of cholestanol was found (5.2 μg/mL, reference range 1.62-3.08). The patient did not show any neuropathy, although T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging showed periventricular white matter. Other classical phenotypes of CTX, such as juvenile cataract, chronic diarrhea, and intellectual disability, were not found. Endovascular repair (EVAR) was successfully performed for the treatment of his saccular type AAA. Atorvastatin 10 mg was used to reduce his LDL cholesterol, although chenodeoxycholic acid was not used due to the lack of neuropathy.'}", "questions": ["What age group does the patient fall into at presentation?"], "ground_truth_arguments": ["63 - year - old"]}
{"id": "CaseReportBench:train-30", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Description': 'The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like “X”-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS).', 'Case presentation': 'A 32-year-old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient’s visit to our hospital. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Oral informed consent was obtained from the patient. On the patient’s maternal side, there was a history of rectal cancer (the patient’s grandmother, an uncle, and an aunt), uterine cancer (a 29-year-old female cousin), rectal cancer with uterine cancer (two aunts), and colon polyposis (a 29-year-old male cousin) ( Figure 1A ). A physical examination showed mild tenderness only in the right lower abdomen. No significant abnormalities were found in serum tumor markers. A colonoscopy revealed a cauliflower-like mass at the beginning of the ascending colon ( Figure 1B ). Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast-enhanced computed tomography (CT) showed ascending colon cancer with intussusception ( Figure 1D ). The preoperative diagnosis was cT3N0M0 colon cancer, according to the TNM classification. On August 27, 2021, the patient underwent laparoscopic radical right hemicolectomy under general anesthesia. During the operation, we found that there were two ICAs derived from the SMA, with the ileocolic vein (ICV) crossing anterior to the SMA ( Figure 2A ). The right colic vein was also absent ( Figure 2B ). The gastrocolic trunk of Henle was draining into the superior mesenteric vein (SMV), which was joined by the right gastroepiploic and colic veins, the anterior superior pancreaticoduodenal vein, and the superior right colic vein ( Figure 2C ). Furthermore, the SMA and SMV were found to be accompanied like “X”-shaped variant ( Figure 2D ). As we saw in the surgery，abdominal contrast-enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery (RCA) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C ). We summarized the schematic diagram of vascular variation of this patient ( Figure 3D ). The patient was discharged on the fourth day after surgery. Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient’s tumor sample ( Figure 5C,5D ). Given the patient’s family history of cancer, we highly suspected Lynch syndrome (LS). Next-generation sequencing (NGS), performed by 3D Medicines Inc. (Shanghai, China), was used to analyze tumor and blood samples from the patient. As shown in Figure 6, the results revealed MLH1 c.885-1_893del, which may represent a change in the conformation of the acceptor splicing site, which may have impeded mRNA formation, eventually leading to deficient mismatch repair. Seven weeks after surgery, the patient was administered a regimen of adjuvant chemotherapy with CapeOX (day 1, oxaliplatin 130 mg/m 2, day 1 to 14 capecitabine 1,000 mg/m 2, po, twice a day, every 3 weeks) for four cycles. Four months after the end of chemotherapy, CT reexamination showed no tumor recurrence ( Figure 7 ).'}", "questions": ["What abdominal symptoms did the patient report, including the nature of the pain and any changes in stool habits?", "Which gastrointestinal symptoms were absent in the patient (e.g., abdominal distention, nausea, vomiting, constipation, diarrhea)?", "What findings were noted on physical examination of the abdomen, particularly regarding tenderness and its location?"], "ground_truth_arguments": ["intermittent abdominal pain accompanied by changes in stool habits", "mild tenderness in the right lower abdomen", "intermittent abdominal pain accompanied by changes in stool habits", "no abdominal distention, nausea, vomiting, constipation, or diarrhea", "mild tenderness only in the right lower abdomen"]}
{"id": "CaseReportBench:train-391", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'CASE REPORT': 'A 5 year-old boy was referred to the Pediatric Dentistry Clinic with the complaint of \"a small ball that appeared in the mouth\". During the anamnesis, the patient was diagnosed as having hypophosphatemic vitamin D-resistant rickets. The child was the third twin; however, the parents as well as the siblings, did not have the metabolic disorder. The medicines taken by the patient were calcitriol and phosphate supplements. He presented short stature and several skeletal abnormalities. Clinical examinations revealed fistula at the periapical region of primary maxillary left lateral incisor without caries or trauma ( Figure 1 ). The patient presented complete primary dentition and none of the teeth examined showed evidence of caries ( Figure 2A-B ). Radiographic examinations included periapical, panoramic and occlusal views showing pulp chambers enlarged, with pulp horns extending to the dentino-enamel junction, poorly defined lamina dura and hypoplastic alveolar ridge ( Figure 2C ). The patient presented a large physiologic wear of the incisors, geographic tongue and primary mandibular right lateral incisor (#82) and canine (#83) with crown alteration ( Figure 3A-B ). There were areas of rarefaction around the apices of the primary maxillary right and left central incisor (#51,61), primary maxillary right and left lateral incisor (#52,62), primary maxillary right and left canine (#53,63) and primary maxillary right and left first molar (#54,64), primary mandibular right and left central incisor (#81,71) ( Figure 4 and 5A-B ). Initially, two sections of management were performed. The treatment was divided into two phases: at first, the extraction of the teeth was performed: #51, 61, 81 and 71. At the second phase, endodontic treatment of the teeth: #52, 62, 53 and 63. These procedures were executed with local anesthesia and rubber dam isolation. The root canals were submitted to preparation with Kerr files and dressing with paramonoclorofenol (Biodinâmica LTDA, Brazil) for 48 hours. Canals were filled with zinc oxid-eugenol and iodoform paste and restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA). During the aforementioned treatment, primary mandibular right first molar (#84), primary maxillary right and left first molar (#54,64) and primary mandibular left second molar (#75) showed periapical fistula without evidence of caries or trauma in a short-term. These teeth were extracted. However, the child was constantly sick and did not attend the consultations. In the other teeth, the primary mandibular right second molar (#85), lateral incisor and canine (#82,83), primary maxillary right and left second molars (#55,65), primary mandibular left first molar and lateral incisor and canine (#74,73,72), the choice of treatment was to open the pulp chambers and make a dressing with formocresol (Biodinâmica LTDA, Brazil). After a 7-day period, the dressing with formocresol was removed and the root instrumentation was performed and filled with zinc oxid-eugenol and iodoform paste, afterwards the teeth were restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA) ( Figure 6 ). In order to maintain the space of primary maxillary right and left second molars and primary mandibular right second molar, a fixed space-maintainer was made and cemented with resin modified glass ionomer cement (Rely X, 3M/ESPE, USA) ( Figure 7A-B ). The postoperative clinic course was uneventful and after six months of follow-up, the child did not show clinical abscesses.'}", "questions": ["What oral complaint did the patient report when first seen at the clinic?", "What abnormality was identified at the periapical area of the primary maxillary left lateral incisor, and were caries or trauma involved?", "How was the overall condition of the patient's primary dentition described, particularly regarding the presence of caries?"], "ground_truth_arguments": ["small ball that appeared in the mouth", "fistula at the periapical region of primary maxillary left lateral incisor without caries or trauma", "complete primary dentition and none of the teeth examined showed evidence of caries"]}
{"id": "CaseReportBench:train-316", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'A 52-year-old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene. Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme. We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme. After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What seizure‑related diagnoses are reported for the patient?"], "ground_truth_arguments": ["epilepsy"]}
{"id": "CaseReportBench:train-105", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Cases': 'The older patient was 20 years old. She was a product of a full-term spontaneous vaginal delivery at home. She was found to have severe virilized external genitalia: a phallic-like structure with hypospadias and incompletely fused labioscrotal folds. She was raised and named as a boy and no medical advice was sought at that time. Her parents reported that she had behaved as a female since early childhood. She was interested in playing with girls and in girl’s games, although she studied at male schools. She spent most of her time with her girlfriends and felt most comfortable when she dressed as a female. She was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation. Physical examination showed a short male-looking adolescent with acne and Tanner stage IV breast development. Her height was 133 centimeters. Her blood pressure was 140/88. Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An adrenocorticotropic hormone (ACTH) stimulation test showed a baseline cortisol (F) level of 28 nmol/L, ACTH of 201 ng/mL (normal, 0–46), 11-deoxycorticosterone (11-DOC) of 20 nmol/L (normal, 0.49–3.3), 17-hydroxyprogesterone (17-OHP) of 17 nmol/L and testosterone (T) of 7 nmol/L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol/L, the 11-DOC level was 141 nmol/L (normal, 2.2–6.8) and the 17-OHP level was 22 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X-ray. Examination under anaesthesia combined with cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus. Based on her biochemical and radiological evaluation, she was diagnosed as having 11-hydroxylase deficiency and was started on hydrocortisone 10 mg twice a day. She was evaluated by the pediatric psychiatrist who clearly confirmed her female gender identity and her strong wish to be converted to a female. Feminizing genitoplasty (clitoral reccesion) was performed at the age of 16 years and she was given a female name. She admitted her strong desire to get married and to be a mother. The younger patient was 16 years old. He was born at home and raised and named as a boy based on the appearance of the external genitalia. His parents reported that he behaved as a male and was proud of that. He was interested in playing with boys and in boy’s sports. He was dressed as a boy and had a short haircut. He was referred to our clinic at the age of 13 years. Physical examination showed a short stature, a masculine appearance, acne and Tanner stage IV pubic hair and stage II breast development. His height was in the fifth centile. His blood pressure was 130/80 mm Hg. Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol/L, an ACTH of 231 ng/mL, 11-DOC of 40 nmol/L, 17-OHP of 18 nmol/L and a T level of 7 nmol/L. Sixty minutes after ACTH stimulation, the F level was 45 nmol/L, 11-DOC was 114 nmol/L and 17-OHP was 20 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years. He was diagnosed as having 11-hydroxylase deficiency and started on hydrocortisone 10 mg twice a day. His final height was 139 centimeters. He was interviewed by the pediatric psychiatrist who clearly confirmed his male gender identity and his strong wish to continue to be raised as a boy. We had several separate meetings with him and his parents and informed them that he would be an infertile man if he decided to continue to be raised as a man and there was a possibility that he would be a fertile women if he converted to his genetic sex. The patient, however, refused to change to his female genetic sex and admitted his strong wish to be a man forever. After more that one year of counseling and intensive psychiatric interview, he and his parents decided on a hysterectomy “to avoid menarche which might affect him psychologically” as his mother said. Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed. Both patients were satisfied by the way they were managed and raised and there were no postoperative psychological complications.'}", "questions": ["What skin condition was observed in the physical examinations of the patients?"], "ground_truth_arguments": ["acne", "acne"]}
{"id": "CaseReportBench:train-613", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'Case Report': 'A 57-year-old woman presented with a history of multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs. The patient was referred from the neurology department for management of these painful masses, which were obstructing her ability to breath and sleep, forcing her to require home oxygen and a wheelchair for ambulation. She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back. Our patient reported a history of myoclonus epilepsy with ragged red fibers (MERRF) syndrome with symptoms including cardiomyopathy, peripheral neuropathy, ataxia, muscle weakness, and myoclonus. She reported multiple family members having MERRF syndrome including her mother, maternal grandmother, maternal great grandmother, sisters, brothers, her sons, and nephews with variable presentations and lipomas. Physical examination found the patient seated in a wheelchair on supplemental oxygen. Multiple symmetric large, variably sized tender masses were easily apparent and palpable around her neck, upper back, upper lateral arms, mid and lower back, lower abdomen, and upper thighs ( Fig 1, Fig 2, Fig 3 ). Fig 1 Frontal view. Patient with symmetric supraclavicular lipomatosis. Fig 2 Posterior neck. Upper back buffalo hump lipomatosis. Fig 3 Lateral view. Symmetric lipomatosis of upper arms.'}", "questions": ["How did the subcutaneous masses impact the patient’s respiratory function and sleep quality?", "In what ways did the identified tissue abnormality affect the patient’s breathing and nighttime rest?", "What types of respiratory or sleep disturbances were associated with the masses in the neck and back region?"], "ground_truth_arguments": ["these painful masses, which were obstructing her ability to breath and sleep"]}
{"id": "CaseReportBench:train-421", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'CASE REPORT': 'A 4-year-male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy. His birth was at full-term from an uneventful pregnancy. On detailed history the child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation. Neurological examination revealed mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child. Skeletal, dental, eye/ fundus examination and eye or limb movements were normal. Child had a normal head circumference for his age. Skin examination showed scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face. Chest radiograph and all routine hematological investigations were normal. Electroencephalogram (EEG) was normal. Patient was sent for the MRI of brain. MRI was done on 0.2 tesla Signa (GE systems, USA) MRI with T2W, T1W, FLAIR sequences in all three planes. The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All these clinical and radiological findings were diagnostic of Sjogren-Larsson syndrome.'}", "questions": ["What skin condition is described in the case report?", "How are the skin lesions characterized, including their appearance, distribution, severity of itching, and age of onset?"], "ground_truth_arguments": ["skin ailment", "scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face"]}
{"id": "CaseReportBench:train-141", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'2. Case Presentation': 'A 19-year-old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents (cousins). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally. On physical examination, there was diffuse palmoplantar keratoderma ( Figure 1 ). Intraoral examination revealed complete edentulous ridges with normal overlying mucosa. In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X-ray, and skull X-ray were normal. She was subsequently provided with artificial dentures and she was a candidate for mandibular bone graft from her skull and dental implants of lower jaw. Complete blood count and liver function tests were also normal. The patient was informed of the indication, and risks and benefits of fiberoptic nasal intubation under sedation. Preoperatively, after careful intravenous catheter insertion, she was premedicated with intravenous midazolam 1 mg and glycopyrolate 0.2 mg. Topical nasal vasoconstriction was achieved with oxymetazolin nasal drop and xylocaine spray 10% in both nostrils. Nasal oxygenation through the nasopharyngeal airway with 100% oxygen was started 3 minutes before the nasal intubation. The patient received a loading dose of dexmedetomidine (Precedex) 1 µg/kg infused over 10 minutes, followed by maintenance dose of Precedex (0.4 µg/kg/h). Gently, she was intubated by fiberoptic. During the awake nasal intubation, the patient’s SpO 2 remained between 97% and 100%. The heart rate varied from 82 to 96 beat/min. Fentanyl (1.5 µg/kg), propofol (2 mg/kg), and cisatracurium (0.15 mg/kg) were used for induction, and general anesthesia was maintained with Sevoflurane, 50% oxygen and 50% nitro oxide. Vital signs were stable during the surgery. Fentanyl (50 µg) and cisatracurium (2 mg) were repeated every 45 minutes. At the end of the surgery, the patient was extubated when she was fully awake and shifted to post anesthesia care unit (PACU) and had a recovery without any complication. Informed consent was taken from the patient regarding the publication of information in the journal. The patient reviewed the case and gave written permission for the authors to publish the report.', 'Case Presentation': 'We report a 19-year-old girl with palmoplantar hyperkeratosis who presented total loss of her teeth. She was candidate to mandibular bone graft and lower jaw dental implants under general anesthesia.'}", "questions": ["What demographic details and main dermatologic finding are reported for the patient?", "When did the skin manifestations begin, and when did the dental loss become evident in the patient’s history?", "What familial and genetic information is provided, including parental relationship and the health status of siblings?", "How did the patient’s permanent and deciduous teeth erupt and what was the pattern of their loss?", "Which syndrome is diagnosed based on the combination of palmoplantar hyperkeratosis and early tooth loss?", "What key aspects of the patient’s presentation are highlighted in the case summary?"], "ground_truth_arguments": ["A 19 - year - old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents ( cousins ). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally", "We report a 19 - year - old girl with palmoplantar hyperkeratosis who presented total loss of her teeth"]}
{"id": "CaseReportBench:train-314", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Based on the clinical, laboratory, and histopathological findings, what general type of condition was concluded for the patient?"], "ground_truth_arguments": ["we made the diagnosis of H syndrome"]}
{"id": "CaseReportBench:train-71", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case presentation': \"This is a 20-year-old female with a 6-month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days. Her vital signs on admission showed uncontrolled hypertension (BP = 148/118 mm Hg) and tachycardia (HR = 120 bpm). She was unable to eat during the last few days. On the second day of her admission, she had two generalized tonic–clonic seizures. She received lorazepam and levetiracetam, and her clinical seizures resolved; however, she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region. The patient was transferred to the ICU for blood pressure control and was started on treatment with acyclovir, antihypertensive medications, and antibiotics. She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid (CSF) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus . The brain MRI showed PRES ( Fig. 1 ). Because the stat EEG showed LPDs + F, a highly epileptogenic pattern, cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording. Therefore, clinical and electrographic seizures completely subsided with treatment. Acyclovir was discontinued, and high dose steroids were started, considering the possibility of immunological and inflammatory etiologies. The patient showed clinical improvement, but her abdominal pain persisted, and the diagnosis of an acute porphyria was suspected. Urine, then serum and fecal porphyrins were requested. The results were as follows: urine PBG level was 177.4 μmol/L (reference: 0 to 0.88 μmol/L), serum porphyrin level was 58 nmol/L (reference: 0 to 15 nmol/L), fecal coproporphyrin was 18 nmol/g (reference: 0 to 45 nmol/g), and fecal protoporphyrin was 10 nmol/g (reference: 0–100 nmol/g). Taken together, the highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels, were suggestive of AIP. The patient's abdominal pain resolved in less than 24 h with carbohydrate (glucose) loading and highly caloric diet. Therefore, intravenous hemin was not necessary at that time. She was discharged home in stable conditions and offered to follow up at a porphyria center of her choice for further confirmatory genetic testing, management, and counseling. The patient was seen in our epilepsy outpatient clinic one month later. She was not taking any medications. She was asymptomatic, and her neurological exam was normal. A follow-up brain MRI showed remarkable improvement.\"}", "questions": ["What were the results of the head CT, cerebrospinal fluid analysis (including PCR for HSV, VZV, Lyme disease, and Cryptococcus), and what did the initial brain MRI show?", "What were the measured levels and reference ranges for urine PBG, serum porphyrin, fecal coproporphyrin, and fecal protoporphyrin?", "How were the porphyrin test results (urine PBG, serum porphyrin, fecal porphyrins) interpreted in terms of the suspected diagnosis?", "What findings were observed on the follow‑up brain MRI?"], "ground_truth_arguments": ["Head CT was normal, cerebral spinal fluid ( CSF ) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus. The brain MRI showed PRES", "Urine, then serum and fecal porphyrins were requested. The results were as follows : urine PBG level was 177.4 μmol / L ( reference : 0 to 0.88 μmol / L ), serum porphyrin level was 58 nmol / L ( reference : 0 to 15 nmol / L ), fecal coproporphyrin was 18 nmol / g ( reference : 0 to 45 nmol / g ), and fecal protoporphyrin was 10 nmol / g ( reference : 0–100 nmol / g", "highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels", "follow - up brain MRI showed remarkable improvement."]}
{"id": "CaseReportBench:train-578", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case Presentation': 'A 22-year-old Hispanic female with a past medical history of dysmenorrhea and recurrent urinary tract infections (UTIs), previously diagnosed by her primary care physician, presented with an 8-day history of no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation. She had tried multiple laxatives for symptom relief. She also reported frequent antibiotic usage, most recently ciprofloxacin, for recurrent UTIs. She had previously been prescribed an oral contraceptive for dysmenorrhea, but it was recently discontinued due to severe nausea and negligible improvement of her abdominal pain. On presentation, she was afebrile (36.7°C), had a normal heart rate (85 beats per minute), normal respiratory rate (16 breaths per minute), and was normotensive (121/80 mmHg). On physical examination, the patient was alert and oriented to time, place, and person without any objective signs of anxiety, depression, psychosis, or other appreciable psychiatric disturbances. The abdomen was soft, nondistended, with mild upper abdominal and periumbilical tenderness. Laboratory examinations were remarkable only for hyponatremia of 130 mEq/L and hypoalbuminemia at 3.4 g/dL. Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm/kg and urine sodium was 100 mEq/L, indicating a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Her initial computerized tomography (CT) scan of the abdomen and pelvis ( Figure 1 ) revealed a diffusely dilated small bowel filled with fecal matter and marked colonic distention with cecal dilatation measuring 9 cm. She was kept nil per os, except for medications, and a nasogastric tube was placed for bowel decompression. A colonoscopy found only granular and punctate erythematous mucosa in the rectum and sigmoid colon with mild nonspecific ileitis and successfully decompressed the dilated colon. A few days after decompression, she developed several watery bowel movements and continued to have abdominal pain. Rapid stool studies were obtained and returned positive for Clostridium difficile antigen and toxin A&B. She was treated with oral vancomycin for 10 days. A repeat CT scan of her abdomen ( Figure 2 ) noted no further small bowel dilation, free air, or free fluid. CT enterography showed no bowel wall thickening or imaging features to suggest inflammatory bowel disease. Her appetite improved, but her abdominal pain persisted despite the antibiotic course, and pain remained out of proportion to her physical examination. The differential was broadened to include AIP. A random urine PBG was elevated at 99.9 mg/g (normal < 0.22 mg/g), with a urine delta aminolevulinic acid (ALA) elevated at 71.9 mg/g (normal < 5.4 mg/g). The fractionation of porphyrins in plasma ( Table 1 ) and urine ( Table 2 ) was suggestive of a biochemical diagnosis of AIP. Intravenous (IV) hematin 1 mg/kg/d and IV dextrose were given for 3 days. After hematin/dextrose therapy, her abdominal pain and bowel symptoms resolved. On subsequent questioning, it was found that she had no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures within our medical institution. She improved clinically and was later discharged with education on how to reduce AIP acute attacks and followed as an outpatient by hematology. Two weeks after discharge, the patient was seen by her primary care physician and noted significant improvements in her appetite and abdominal pain without recurrence of constipation or diarrhea.'}", "questions": ["What preexisting gynecologic and urinary conditions did the patient have?", "What serum sodium concentration was reported, and what electrolyte abnormality does this represent?", "What were the results of the urine analysis and reflex culture, specifically regarding leukocyte esterase, nitrites, urine osmolality, and urine sodium?", "What negative personal and family medical histories were documented?"], "ground_truth_arguments": ["dysmenorrhea and recurrent urinary tract infections ( UTIs ),", "recurrent UTIs", "dysmenorrhea", "hyponatremia of 130 mEq / L", "Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm / kg and urine sodium was 100 mEq / L", "no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures"]}
{"id": "CaseReportBench:train-76", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE PRESENTATION': 'A 31‐year‐old mentally disabled man was referred to our neurologic clinic with a gradually worsening gait disorder, impaired balance, and repeated falling episodes. The patient was the third child of consanguinity marriage. He was delivered following a normal term pregnancy with normal birthweight and height. History of atheromatous disease or intractable infantile‐onset diarrhea was not distinguished. At the age of five, he developed a blurred vision, which was diagnosed as a bilateral cataract. The patient was a school dropout due to intellectual and neuropsychiatric disability. He had developmental delays in the mental functioning and speech with a normal physical growth. At the age of 20, he developed bilateral tendinous swelling of the posterior part of the ankles that worsened over time. He complained of severe gait disturbance and ataxia since 3–4 years ago. He had frequent falling episodes resulting in multiple bone fractures. Gait disorder worsened gradually, and he started using a wheelchair. On physical examination, he had bilateral and symmetrical painless hypertrophy of the Achilles tendons (Figure 1 ). Neurological examination showed muscle weakness predominant in the distal muscles of upper and lower limbs (MRC score of 3 in the foot dorsiflexion and MRC score 2 in the finger adduction and abduction), hypertonia, brisk deep tendon reflexes, bilateral Babinski sign, and ankle clonus. The finger to nose was normal, but the heel to shin was abnormal bilaterally. The laboratory results were normal for the thyroid, liver, and kidney function, serum electrolytes, and triglyceride and cholesterol level. A brain magnetic resonance imaging (MRI) discovered cerebral and cerebellar atrophy, high‐intensity areas in the dentate nuclei, and symmetric hyperintensities in the cerebellar deep white matter and paraventricular white matter on T2‐weighted (T2W) and fluid‐attenuated inversion recovery (FLAIR) images with corresponding hypointensities on T1‐weighted (T1W) images (Figure 2 ). Ultrasonography demonstrated focal areas of hypoechogenicity on the bilateral Achilles tendons measuring 3, 7, 9, 12, and 16 mm on the right and 8, 15, 11, and 14 mm on the left side. Whole‐exome sequencing identified a homozygous splicing mutation, NM_000784: exon3: c.465C>A; (p. Tyr155*) in CYP27A1 gene compatible with a diagnosis of CTX. The patient was married, but he was infertile. Sex hormone tests were normal. Testicular ultrasound showed that the size of the testes was in the lower limit of normal range with a normal epididymis and vein plexus. Semen analysis showed azoospermia. Analysis of the most common Y chromosome microdeletions using multiplex polymerase chain reaction and gel electrophoresis showed no microdeletions in AZFa, AZFb, and AZFc sub‐regions of the long arm of chromosome Y.'}", "questions": ["What is the confirmed diagnosis for the patient?"], "ground_truth_arguments": ["diagnosis of CTX ."]}
{"id": "CaseReportBench:train-256", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case presentation': 'We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia. She received critical care symptomatic management including mechanical ventilation. The diagnosis was based on a positive urine test for porphobilinogen and confirmed by the presence of a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). This work has been reported in line with the SCARE criteria . A 24 year-old- single female patient was admitted because of right lower abdominal pain and distension for 2 weeks. The pain was colicky, episodic, with no precipitating factors and only relieved after bowel motion. She had no constitutional symptoms of chronic illness. She was not on any medications and her social history was unremarkable. Her menstrual cycle was regular and she was menstruating one day after admission. Physical examination revealed a thin patient in mild pain distress with normal vital signs. Her abdomen was soft and lax with normal bowel sounds. Routine laboratory tests including CBC and renal and liver function tests were normal. Serum transaminases remained normal during her hospital stay. Aspartate aminotransferase (AST, SGOT) range was 18–33 U/L (normal range: 15–37 U/L). Alanine aminotransferase (ALT, SGPT) range was 25–51 U/L (normal range: 14–63 U/L). On admission, level of serum sodium (Na) was normal: 138 mEq/L (normal range 135–145 mEq/L) and remained normal (range: 135–139 mEq/L) until the 5th postoperative day (see below). Plain abdominal X-ray and abdominal computed tomography (CT) showed a distended cecum located in the pelvis with fecal impaction; the rest of the viscera were unremarkable. These findings were consistent with mobile cecum syndrome. The patient was scheduled for laparoscopy and possible laparotomy. The only abnormality during laparoscopy was that the cecum and ascending colon were not attached to posterior abdominal wall. The procedure was converted to laparotomy. Right hemi-colectomy was performed. She was kept on epidural analgesia, intravenous (IV) fluids and nil by mouth for four days and had a smooth post-operative course. After surgery, she received intravenous (IV) 5% dextrose/0.9% NaC) three liters/day (her weight was 48 kg). In addition, her pain was controlled by epidural analgesia of lidocaine and fentanyl. The histology revealed normal colon. On the 5th postoperative day, oral intake was resumed and epidural analgesia was discontinued. Eight hours later, she had a sudden deterioration of consciousness level and became unresponsive with a Glasgow Coma Scale of 7/15. Her pupils were dilated and had a sluggish reaction to light. The patient was immediately intubated, mechanically ventilated, resuscitated, and admitted to the intensive care unit (ICU). Blood work up revealed severe hyponatremia; serum Na: 107 mEq/l with normal renal and liver function tests. Our differential diagnoses for the severe hyponatremia included drug intoxicity, encephalitis, and salt losing nephropathy. Consultations to neurology and psychiatry were made and they advised brain CT scan and magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. These tests and septic work-up were normal. She was extubated two days later. At this stage, she started to complain of acute abdominal pain and developed altered mental status, personality changes, visual and auditory hallucinations with euphoric and aggression episodes despite correction of serum Na. The presence of abdominal pain, neurological and psychiatric symptoms and unexplained severe hyponatremia raised the suspicion of AIP. The diagnosis of AIP was based on the presence of high PBG in the urine (test was done at another center). At no time, her urine was dark. In retrospect, the family history showed that two of her cousins (from mother side) had AIP. The patient condition improved markedly after proper pain control and high carbohydrate intake. We referred her to a higher center where she was found to have a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). There, she received premenstrual regime of IV hematin (heme arginate) 4 mg/Kg body weight/day for three days. She had four recurrent milder attacks in the form of abdominal and back pain and confusion and was treated with similar regime of hematin. Thereafter, she was kept on once monthly prophylactic IV hematin 4 mg/Kg body weight/day for three days. Now, one and a half years after discharge from our service, she is doing fine and on no hematin treatment.'}", "questions": ["Did the urine analysis detect porphobilinogen?", "Was any mutation identified in the HMBS gene?", "What were the findings of the routine laboratory tests (CBC, renal and liver function, AST, ALT, and serum sodium) on admission and up to postoperative day 5?", "What did the abdominal plain X‑ray and computed tomography reveal regarding the cecum and other viscera?", "Did the histopathology of the resected colon reveal any abnormalities?", "How did the serum sodium level change during the episode of severe hyponatremia?", "What were the results of the brain imaging studies (CT, MRI) and cerebrospinal fluid analysis performed during the work‑up?"], "ground_truth_arguments": ["positive urine test for porphobilinogen", "presence of a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene ( c.760delC p Leu254 )", "Routine laboratory tests including CBC and renal and liver function tests were normal. Serum transaminases remained normal during her hospital stay. Aspartate aminotransferase ( AST, SGOT ) range was 18–33 U / L ( normal range : 15–37 U / L ). Alanine aminotransferase ( ALT, SGPT ) range was 25–51 U / L ( normal range : 14–63 U / L ). On admission, level of serum sodium ( Na ) was normal : 138 mEq / L ( normal range 135–145 mEq / L ) and remained normal ( range : 135–139 mEq / L ) until the 5th postoperative day", "Plain abdominal X - ray and abdominal computed tomography ( CT ) showed a distended cecum located in the pelvis with fecal impaction; the rest of the viscera were unremarkable", "The histology revealed normal colon", "Blood work up revealed severe hyponatremia; serum Na : 107 mEq / l with normal renal and liver function tests", "brain CT scan and magnetic resonance imaging ( MRI ), and cerebrospinal fluid analysis. These tests and septic work - up were normal", "presence of high PBG in the urine", "she was found to have a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene ( c.760delC p Leu254"]}
{"id": "CaseReportBench:train-338", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made. Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years. There was no other significant positive clinical findings. Case three was a 14-year-old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia. Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth. On examination, he had molluscum contagiosum lesions on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case. Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis. Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern. The features of all these five cases have been summarized in Table 1 .'}", "questions": ["What neurodevelopmental or cognitive impairments were reported in any of the patients?"], "ground_truth_arguments": ["mental retardation"]}
{"id": "CaseReportBench:train-517", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made. Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years. There was no other significant positive clinical findings. Case three was a 14-year-old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia. Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth. On examination, he had molluscum contagiosum lesions on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case. Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis. Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern. The features of all these five cases have been summarized in Table 1 .'}", "questions": ["How are the hypo‑ and hyperpigmented lesions described regarding symptom presence (e.g., asymptomatic) and anatomical distribution (e.g., whole body, extremities, acral areas)?", "For the case(s) where the initial lesion site and progression timeline are reported, what is the initial location and over what period did the lesions spread?", "Is any history of photosensitivity, chemical exposure, or drug intake mentioned in relation to the skin findings?", "What observations are reported concerning skin atrophy, telangiectasia, and the condition of the palms, soles, mucous membranes, hair, and nails?", "Summarize the histopathological findings for hyperpigmented macules and for hypopigmented macules.", "Describe the pigmentation pattern observed on the palms and soles (e.g., normal, mottled, similar to lesions elsewhere).", "List any additional cutaneous lesions or viral skin conditions mentioned (e.g., verruca vulgaris, molluscum contagiosum).", "What craniofacial dysmorphic features (e.g., broad nasal bridge, long philtrum, high‑arched palate) are noted in the patients?", "What recurrent skin infections or complications (e.g., pyodermas) are described?", "How does the histopathology of later cases compare to that of the first case?", "For patients who are siblings or otherwise related, what lesion characteristics are reported as shared between them (e.g., size variation, distribution across the body)?", "Is there any description indicating that lesions are distributed uniformly across the body?"], "ground_truth_arguments": ["asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body", "initial lesions started in the chest and then spread to the entire body in 2 years", "no history of photosensitivity", "skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal", "Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin", "asymptomatic multiple hypo and hyperpigmented macules all over the body", "similar lesions all over the body", "palms and soles also showed similar mottled pigmentation", "multiple verucca vulgaris over the left arm and dorsum of hands", "similar lesions all over the body", "Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth", "molluscum contagiosum lesions on the face", "Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate", "Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body", "Histopathology showed similar features as that of the first case", "asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities", "His palms and soles were normal.", "Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer"]}
{"id": "CaseReportBench:train-52", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What is the patient's age in years at the time of presentation?"], "ground_truth_arguments": ["12 - year - old"]}
{"id": "CaseReportBench:train-518", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["For each case, at what point relative to the CTX diagnosis was chenodiol (chenodeoxycholic acid) therapy initiated?", "For each case, describe whether the patient has taken chenodiol continuously since initiation, including any interruptions and their durations."], "ground_truth_arguments": ["prompt initiation of chenodiol therapy . She has been on chenodiol consistently since the diagnosis at age 27 .", "She started chenodiol at the time of the diagnosis", "Chenodiol ( chenodeoxycholic acid ) therapy was initiated at diagnosis , and she has remained on chenodiol since that time"]}
{"id": "CaseReportBench:train-608", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case report': 'SH is a 44-year-old female diagnosed with mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure. After her diagnosis was made, she was initially followed by Neurology; however she was subsequently referred to our cardiomyopathy clinic secondary to progressive left ventricular hypertrophy (LVH) on echocardiogram and the known association between MELAS and cardiac disease. Prior to evaluation by our clinic, she had a clinical diagnosis of MELAS but evaluation by our cardiovascular genetics team yielded positive results for the A-to-G transition at nucleotide 3243 (m.3243A > G) of the mitochondrial genome, with 25% heteroplasmic deleterious mutation in MT-TL1, a mitochondrial leucine transfer RNA gene, the most common mutation underlying MELAS. At the time of presentation to our clinic, SH had carried the diagnosis of MELAS for 11 years and her symptoms had progressed significantly so that she was no longer able to be employed and her husband became her primary caretaker. Her clinical status included multiple medical problems related to her MELAS diagnosis: sensorineural hearing loss, myopathy, bilateral ophthalmoplegia, ptosis, seizures and stroke-like episodes with concern for dementia. Her family history is significant for a 12-year-old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss. In addition to a clinical exam and genetic evaluation, cardiac work-up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non-sustained atrial tachycardia ( Fig. 1 ). From a cardiac imaging perspective, an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub-epicardium of approximately 25–50% in thickness in the inferior segment at the base, inferior to lateral segments at the mid-ventricle and lateral segment of the apex, with sparing of the endocardium and septum ( Fig. 1 A and 1 B). Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes (R > L), and moderate cerebellar atrophy with extensive white matter disease. Monitoring laboratory evaluation yielded no significant abnormalities with the exception of a slightly elevated brain natriuretic peptide of 305 (normal < 200 ng/L). Her liver and kidney functions were normal and there was no hyperglycemia. From a cardiac management perspective, she has been maintained on Atenolol 25 mg twice daily and aspirin 325 mg once daily.'}", "questions": ["What does the document state regarding the presence or absence of hyperglycemia or diabetes in the patient?"], "ground_truth_arguments": ["no hyperglycemia."]}
{"id": "CaseReportBench:train-448", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["At what age was each patient diagnosed with pseudoxanthoma elasticum (PXE)?"], "ground_truth_arguments": ["diagnosed with PXE at 18 years of age .", "diagnosed with PXE at 20 years of age", "was diagnosed with PXE at 8 years of age .", "diagnosed with PXE at 41 years of age ."]}
{"id": "CaseReportBench:train-298", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case presentation': \"This is a 20-year-old female with a 6-month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days. Her vital signs on admission showed uncontrolled hypertension (BP = 148/118 mm Hg) and tachycardia (HR = 120 bpm). She was unable to eat during the last few days. On the second day of her admission, she had two generalized tonic–clonic seizures. She received lorazepam and levetiracetam, and her clinical seizures resolved; however, she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region. The patient was transferred to the ICU for blood pressure control and was started on treatment with acyclovir, antihypertensive medications, and antibiotics. She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid (CSF) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus . The brain MRI showed PRES ( Fig. 1 ). Because the stat EEG showed LPDs + F, a highly epileptogenic pattern, cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording. Therefore, clinical and electrographic seizures completely subsided with treatment. Acyclovir was discontinued, and high dose steroids were started, considering the possibility of immunological and inflammatory etiologies. The patient showed clinical improvement, but her abdominal pain persisted, and the diagnosis of an acute porphyria was suspected. Urine, then serum and fecal porphyrins were requested. The results were as follows: urine PBG level was 177.4 μmol/L (reference: 0 to 0.88 μmol/L), serum porphyrin level was 58 nmol/L (reference: 0 to 15 nmol/L), fecal coproporphyrin was 18 nmol/g (reference: 0 to 45 nmol/g), and fecal protoporphyrin was 10 nmol/g (reference: 0–100 nmol/g). Taken together, the highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels, were suggestive of AIP. The patient's abdominal pain resolved in less than 24 h with carbohydrate (glucose) loading and highly caloric diet. Therefore, intravenous hemin was not necessary at that time. She was discharged home in stable conditions and offered to follow up at a porphyria center of her choice for further confirmatory genetic testing, management, and counseling. The patient was seen in our epilepsy outpatient clinic one month later. She was not taking any medications. She was asymptomatic, and her neurological exam was normal. A follow-up brain MRI showed remarkable improvement.\"}", "questions": ["What acute kidney infection was diagnosed in the patient during admission?"], "ground_truth_arguments": ["acute pyelonephritis,"]}
{"id": "CaseReportBench:train-423", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}", "questions": ["What electrolyte levels (sodium and potassium) were reported in the patient's laboratory tests?", "How did the patient's adrenal hormone production and ACTH concentration compare to normal expectations?", "What did imaging studies (CT, ultrasonography, MRI) reveal about the adrenal glands and the location of the gonads?", "What abnormalities were identified in the chromosomal analysis and StAR gene sequencing?", "What definitive diagnosis was assigned to the patient based on the clinical and genetic findings?", "What histological characteristics of the seminiferous tubules and Leydig cells were observed under light microscopy?", "What ultrastructural features of Leydig cells with excessive lipid droplets were described by electron microscopy?", "Which steroidogenic enzymes were evaluated by immunostaining and Western blot, and what expression pattern was found in the patient's Leydig cells compared to control testes?", "What type of control tissue was used for comparison in the immunohistochemical analysis?"], "ground_truth_arguments": ["Laboratory tests revealed severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).", "Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg / mL ( normal 7.2–63.3 pg / mL ). CT showed enlargement of bilateral adrenal glands ( Fig. 1 a ). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI ( Fig. 1 b ). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p. Q258X and p. D246fs. From these results, lipoid CAH was diagnosed.", "Histopathological findings ' : ' Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids ( Fig. 2 c ). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy ( Fig. 2 d ). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP / SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5 ). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry ( Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient ( data not shown ). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD"]}
{"id": "CaseReportBench:train-293", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': 'The patient presented at age seven years with intermittent vomiting, diarrhea, constipation, weight loss and fatigue that has persisted for over 18 months. Routine work-up showed significant metabolic acidosis with low serum bicarbonate concentrations. He was started on oral sodium citrate and admitted for evaluation, which revealed low serum glucose of 3.05 mmol/L (55 mg/dL) and very low plasma l -carnitine (total carnitine:7 μmol/L, reference range: 25–69). Serum creatine phosphokinase (CK) and transaminases were elevated and continued to increase as he clinically deteriorated, with CK peaking at 202 μkat/L (12,086 U/L), AST at 341 U/L and ALT at 190 U/L. Ophthalmologic and audiologic exams were normal. Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation disorders. The patient had started on carnitine and cornstarch but continued to deteriorate, with multiple admissions for ketotic hypoglycemia and severe lactic acidosis. Brain magnetic resonance imaging was normal, while brain magnetic resonance spectroscopy (MRS) showed lactate peaks in the left basal ganglion and lateral ventricle. As this finding was suggestive of a mitochondrial disorder, treatment with coenzyme Q10, riboflavin, creatine monohydrate, alpha-lipoic acid, and medium chain triglyceride (MCT) oil was initiated, while continuing carnitine supplementation. Leucovorin was later added due to a low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate level. At age eight, he required a gastric feeding tube (G-tube) placement for malnutrition and continued weight loss. The urine organic acid profile was notable for elevations of lactate, ethylmalonate, 3-methylglutaconate, and branched-chain ketoacids, suggestive of mitochondrial dysfunction. Cultured skin fibroblast testing was performed for suspected defects in fatty acid oxidation, pyruvate carboxylase (EC 6.4.1.1), and pyruvate dehydrogenase complex (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4) with normal results . Analysis of acylcarnitines in cultured skin fibroblasts incubated with palmitic acid and l -carnitine (in vitro probe assay) showed marked elevations of long-chain species, suggestive of carnitine palmitoyltransferase II or carnitine–acylcarnitine translocase deficiency. CSF analysis showed mild elevation of lactate of 3.1 mmol/L (< 2.8), and a low normal level of 5-methyltetrahydrofolate. Transaminitis was initially attributed to a possible GSD; glycogen content was elevated in both liver (10%; control range 3.3 +/− 1.7%) and muscle (3.0%; control range 0.94 +/− 0.55). However, sequencing of PHKA1 and PHKG2 genes (GSD IX) and AGL gene (GSD III) was normal. Activities of debranching enzyme (EC 2.4.1.25 GSD III) and hepatic phosphorylase kinase (GSD IX, EC 2.7.11.19) in the liver and muscle, and glucose-6-phosphatase (GSD Ia, EC 3.1.3.9) in the liver were also normal. Further evaluation for a suspected mitochondrial disorder revealed normal electron transporter chain (ETC) activity in cultured skin fibroblasts. Muscle histopathology demonstrated prominent granular red staining of the fibers with a trichrome stain and numerous mitochondria aggregates by electron microscopy, characteristic of a mitochondrial myopathy ( Fig. 1 ). ETC testing on frozen muscle revealed deficient complex III activity of 455 (mean 1461, standard deviation 473); mtDNA sequencing of the muscle sample revealed a 9 basepair deletion with loss of 3 amino acids Leu-Ala-Thr (m.15319_15327delCCTAGCAAC; p.Leu192_Thr194del, Fig. 2 ) in the MT-CYB gene encoding cytochrome b subunit of complex III, with > 90% mutant load, confirming complex III deficiency. MtDNA sequencing in the liver and blood did not reveal the mutation, although low heteroplasmy for the mutation was detected in uncultured skin fibroblasts. Since the diagnosis, ongoing cardiac evaluations to monitor for cardiomyopathy or rhythm disturbance have been normal. The child dramatically improved with the start of G-tube feeding and dietary supplements, with increased energy level, improved exercise tolerance and progress in academic performance. Previously confined to a wheel chair, he started to walk independently and actively. Lactic acid, transaminases and CK levels have stabilized, although lactate showed occasional elevations as high as 11 mmol/L without symptoms of metabolic decompensation. His G-tube was removed at age 12 years and he stopped taking supplements, and he continues to do remarkably well physically.'}", "questions": ["What laboratory results demonstrated significant metabolic acidosis and low serum bicarbonate in the patient?", "What laboratory abnormalities were noted in the patient's glucose, carnitine, and muscle enzyme measurements?", "How many admissions did the patient have for ketotic hypoglycemia and severe lactic acidosis, and what did brain MRI and magnetic resonance spectroscopy reveal?", "What abnormalities were found in cerebrospinal fluid, specifically regarding lactate and 5‑methyltetrahydrofolate levels?", "What types of metabolites were increased in the urine organic acid analysis, and what general metabolic disorder did they suggest?", "What were the results of cultured skin fibroblast testing for fatty‑acid‑oxidation, pyruvate carboxylase, and pyruvate dehydrogenase, and what did the acylcarnitine probe assay indicate?", "What was observed regarding glycogen accumulation in liver and muscle, and what were the overall results of genetic sequencing and enzyme activity testing for glycogen storage disease subtypes?", "What were the overall findings of electron transport chain activity assessments in cultured fibroblasts and frozen muscle tissue?", "What histopathological features were observed in the muscle biopsy, and how did they characterize mitochondrial myopathy?", "What mitochondrial DNA alteration was identified in muscle, and how did its genetic impact and heteroplasmy differ across tissues?"], "ground_truth_arguments": ["significant metabolic acidosis with low serum bicarbonate concentrations", "low serum glucose of 3.05 mmol / L ( 55 mg / dL ) and very low plasma l -carnitine ( total carnitine:7 μmol / L, reference range : 25–69 ). Serum creatine phosphokinase ( CK ) and transaminases were elevated and continued to increase as he clinically deteriorated, with CK peaking at 202 μkat / L ( 12,086 U / L ), AST at 341 U / L and ALT at 190 U / L.", "multiple admissions for ketotic hypoglycemia and severe lactic acidosis. Brain magnetic resonance imaging was normal, while brain magnetic resonance spectroscopy ( MRS ) showed lactate peaks in the left basal ganglion and lateral ventricle", "a low cerebrospinal fluid ( CSF ) 5 - methyltetrahydrofolate level", "urine organic acid profile was notable for elevations of lactate, ethylmalonate, 3 - methylglutaconate, and branched - chain ketoacids, suggestive of mitochondrial dysfunction. Cultured skin fibroblast testing was performed for suspected defects in fatty acid oxidation, pyruvate carboxylase ( EC 6.4.1.1 ), and pyruvate dehydrogenase complex ( EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4 ) with normal results. Analysis of acylcarnitines in cultured skin fibroblasts incubated with palmitic acid and l -carnitine ( in vitro probe assay ) showed marked elevations of long - chain species, suggestive of carnitine palmitoyltransferase II or carnitine – acylcarnitine translocase deficiency. CSF analysis showed mild elevation of lactate of 3.1 mmol / L ( < 2.8 ), and a low normal level of 5 - methyltetrahydrofolate. Transaminitis was initially attributed to a possible GSD; glycogen content was elevated in both liver ( 10 %; control range 3.3 + /− 1.7 % ) and muscle ( 3.0 %; control range 0.94 + /− 0.55 ). However, sequencing of PHKA1 and PHKG2 genes ( GSD IX ) and AGL gene ( GSD III ) was normal. Activities of debranching enzyme ( EC 2.4.1.25 GSD III ) and hepatic phosphorylase kinase ( GSD IX, EC 2.7.11.19 ) in the liver and muscle, and glucose-6 - phosphatase ( GSD Ia, EC 3.1.3.9 ) in the liver were also normal. Further evaluation for a suspected mitochondrial disorder revealed normal electron transporter chain ( ETC ) activity in cultured skin fibroblasts. Muscle histopathology demonstrated prominent granular red staining of the fibers with a trichrome stain and numerous mitochondria aggregates by electron microscopy, characteristic of a mitochondrial myopathy ( Fig. 1 ). ETC testing on frozen muscle revealed deficient complex III activity of 455 ( mean 1461, standard deviation 473 ); mtDNA sequencing of the muscle sample revealed a 9 basepair deletion with loss of 3 amino acids Leu - Ala - Thr ( m.15319_15327delCCTAGCAAC; p. Leu192_Thr194del, Fig. 2 ) in the MT - CYB gene encoding cytochrome b subunit of complex III, with > 90 % mutant load, confirming complex III deficiency. MtDNA sequencing in the liver and blood did not reveal the mutation, although low heteroplasmy for the mutation was detected in uncultured skin fibroblasts."]}
{"id": "CaseReportBench:train-282", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Presentation': \"Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment. A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5 th percentile), weight 3000 g (<5 th percentile), and head circumference 36.5 cm (5–10 th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance. Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative. The laboratory tests were as follows: serum sodium 102 meq/lit and serum k + level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1 . Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern. Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed. On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25 th percentile), weight 9.5 kg (10–25 th percentile) and head circumference 46 cm (25 th percentile); her neurodevelopment was appropriate for age.\"}", "questions": ["What gastrointestinal and hepatic symptoms were present at the infant’s initial presentation?", "How did the infant’s feeding behavior and weight change during the early course of illness?", "What stool characteristics were reported by the parents and how did they evolve before admission?", "How did the infant’s jaundice and stool color change after treatment, and what was observed at later follow‑up?", "Were any hypoglycemic episodes noted during the follow‑up period after discharge?"], "ground_truth_arguments": ["cholestasis and severe intractable vomiting", "jaundice and vomiting", "recurrent vomiting, poor feeding and cholestasis", "with recurrent vomiting and poor intake which led to poor weight gain.", "Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission", "jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed"]}
{"id": "CaseReportBench:train-113", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}", "questions": ["What urine-related abnormalities are noted for the patient?", "What gynecologic findings are described for the patient?", "What electrolyte disturbances are documented in the patient's laboratory results?"], "ground_truth_arguments": ["dark colour of urine", "frequent urination, blood in the urine", "irregular menstrual cycles", "pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia", "dark colour of urine"]}
{"id": "CaseReportBench:train-285", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["What ocular symptoms did the patient experience, including changes in eyelid position and vision in low light?", "What findings were observed on ophthalmic examination, including any abnormalities of eye movement or the retina?", "What did the fundoscopic examination reveal about the peripheral retina?"], "ground_truth_arguments": ["progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina", "Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina"]}
{"id": "CaseReportBench:train-523", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': \"An eleven month old female child, born of a primigravida mother of non-consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal. There was no similar illness in the family. Her pulse rate was 102/min, blood pressure was 84/58 mm of Hg. and respiratory rate was 25/min. Her weight was 7.9 kg, length was 70 cm and head circumference was 45 cm. There was some pallor. Blisters were present on scalp, face, upper and lower limbs with atrophic scars on scalp and upper limbs along with alopecia. Copper-red discoloration of the two erupted teeth was noted. There was no hepatosplenomegaly. Neurological examination was normal. On the basis of infancy-onset blistering over sun-exposed areas, atrophic scars, red colored urine and teeth without neurological involvement and evidence of arthritis, we reached the provisional diagnosis of CEP. Complete blood count showed mild anemia; Hb-9.2 mg/dl, total leucocyte count-8,200 and platelet count of 1.4 lac/cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2% of circulating erythrocytes (normal upto 2%). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol/mmol of creatinine (normal < 35 nmol/mmol). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method (normal value < 40 mcg/100 ml). Bright red fluorescence was also noted in the urine, teeth and blood under wood's lamp. So, a final diagnosis of congenital erythropoietic porphyria was made. Demonstration of deficiency of UROS activity and genetic study could not be performed due to lack of laboratory facilities.\"}", "questions": ["Describe the developmental history reported for the patient.", "What findings were documented from the neurological examination?", "What does the case report indicate about any neurological involvement?", "Were any abnormal findings observed when a Wood's lamp was used to examine the patient's urine, teeth, or blood?"], "ground_truth_arguments": ["developmental history were normal.", "Neurological examination was normal.", "without neurological involvement", "Bright red fluorescence was also noted in the urine, teeth and blood under wood 's lamp"]}
{"id": "CaseReportBench:train-48", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'CASE REPORT': \"A young stocky built adult patient appearing in early twenties dressed in shirt and pant with a thick moustache and beard accompanied with parents walked inside psychiatry out-patient department (OPD) with a referral from plastic surgery OPD concerning gender affirmation surgery. Patient introduced self in a husky masculine voice as Ms. T, a 21-year old female patient and expressed desire to be named as Mr. T, in further conversation. On interview, parents reported patient to be their eldest daughter born of a non-consanguineous marriage following a full term normal vaginal delivery. Parents reported since early childhood, patient was tomboyish, more comfortable playing with boys, watching wrestling and never showed interest in dolls or playing with younger sister or girls at school. Patient used to wear shirt and skirt to school, but at home used to prefer wearing T-shirt and jeans. From adolescence onwards, patient started to gain weight, developed hirsutism and never attained menarche. Mother had to frequently remove patient's facial hairs by hair removing cream. Patient started to feel attracted towards females though never had any sexual contact. Patient started to develop strong disliking towards self being called as a female, withdrew self from female friends and interest in studies declined; but never verbalised these feelings to anyone. 17 years onwards, after completing high school patient started to express strong resentment. Thereafter, with parents consent patient started to dress as males, stopped removing facial hairs. From 18 years onwards, proclaiming self as Mr. T patient started to work as a salesman. Patient and parents were happy with the new desirable identity. Difficulties faced were using common urinals, feeling ashamed of getting the anatomical sex being disclosed and inability to study further or procure a white collared job because of high school certificate mentioning sex as female. Despite these problems, patient was more comfortable in male gender role and since past 2 years, started seeking help for gender affirmation surgery. Patient appeared to be of average intelligence and had no persistent aggressive, violent or criminal tendencies. There was no past history of taking any hormones exogenously. Examination revealed 65 kg weight, 160 cm height and 116/82 blood pressure. External body habitus was of male and external genitalia was of female. There were no apparent cushingoid features. Karyotyping showed 46XX pattern. Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X-ray were normal. Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17-OH progesterone and dehydro-epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test suggesting diagnosis of non-classical congenital adrenal hyperplasia.\"}", "questions": ["What information is provided about the timing and method of delivery?"], "ground_truth_arguments": ["full term normal vaginal delivery"]}
{"id": "CaseReportBench:train-311", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': \"An eleven month old female child, born of a primigravida mother of non-consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal. There was no similar illness in the family. Her pulse rate was 102/min, blood pressure was 84/58 mm of Hg. and respiratory rate was 25/min. Her weight was 7.9 kg, length was 70 cm and head circumference was 45 cm. There was some pallor. Blisters were present on scalp, face, upper and lower limbs with atrophic scars on scalp and upper limbs along with alopecia. Copper-red discoloration of the two erupted teeth was noted. There was no hepatosplenomegaly. Neurological examination was normal. On the basis of infancy-onset blistering over sun-exposed areas, atrophic scars, red colored urine and teeth without neurological involvement and evidence of arthritis, we reached the provisional diagnosis of CEP. Complete blood count showed mild anemia; Hb-9.2 mg/dl, total leucocyte count-8,200 and platelet count of 1.4 lac/cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2% of circulating erythrocytes (normal upto 2%). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol/mmol of creatinine (normal < 35 nmol/mmol). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method (normal value < 40 mcg/100 ml). Bright red fluorescence was also noted in the urine, teeth and blood under wood's lamp. So, a final diagnosis of congenital erythropoietic porphyria was made. Demonstration of deficiency of UROS activity and genetic study could not be performed due to lack of laboratory facilities.\"}", "questions": ["What are the patient’s age, gender, and parental background (e.g., primigravida mother, consanguinity status)?", "At what age did the recurrent skin blisters first appear and which body sites were initially involved?", "How did the distribution of the blisters evolve over time, and what stages of healing were observed?", "What additional symptom involving urine did the mother notice, and for how long has it been present?", "What information is provided about the child’s birth and developmental history?", "Is there any reported family history of a similar illness?"], "ground_truth_arguments": ["An eleven month old female child, born of a primigravida mother of non - consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal.", "There was no similar illness in the family"]}
{"id": "CaseReportBench:train-597", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["What is the confirmed diagnosis of the infant?", "Is an enzyme deficiency implicated in the diagnosed condition?", "Was a genetic mutation identified to confirm the diagnosis?", "Was a confirmatory test performed to establish the diagnosis?"], "ground_truth_arguments": ["A diagnosis of CAH secondary to 21 - hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies ."]}
{"id": "CaseReportBench:train-473", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Observation': 'An 18-month-old boy born after an uncomplicated full-term pregnancy was hospitalized for psychomotor regression and drug-resistant myoclonic epilepsy. There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected. The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay. Physical examination revealed a macrocephaly of 51 cm with a dysmorphic syndrome consisting of a frontal bossing and a broadening of the nasal bridge. The neurological examination revealed an axial hypotonia with no further optical problems or responsiveness to light. Ophthalmologic examination showed a cherry-red spot without optic atrophy. Cerebral computed tomography (CT) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter (Fig. 1 ). With magnetic resonance imaging (MRI) the thalamus was hyperintense on T1-weighted images and hypointense on T2-weighted images (Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem. Clinical data and thalamic involvement suggest metabolic diseases such GM2 gangliosidosis (e.g. Tay-Sachs and Sandhoff diseases) or GM1 gangliosidosis (e.g. Landing disease), Canavan disease or Alexander disease. Chromatography of amino acids in the blood, urine and cerebrospinal fluid (CSF) was normal and chromatography of organic acids in the urine was also normal. Enzymatic assays were performed in France and revealed a deficiency of both hexosaminidases A and B confirming the diagnosis of Sandhoff disease.'}", "questions": ["What findings were observed on ophthalmologic examination, specifically regarding retinal appearance and optic nerve status?", "What visual or light‑response abnormalities, if any, were noted during the neurological assessment?"], "ground_truth_arguments": ["no further optical problems or responsiveness to light.", "cherry - red spot without optic atrophy"]}
{"id": "CaseReportBench:train-440", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': \"A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission.\"}", "questions": ["What cardiac abnormality was identified on echocardiography?", "What findings were reported from the voiding cystourethrography, spine ultrasound, and clinical assessment for tracheoesophageal fistula?", "What were the results of the initial laboratory tests, neonatal metabolic screening (including 17‑alpha‑hydroxyprogesterone), and chromosome analysis?", "During the adrenal insufficiency workup, what notable laboratory abnormalities were identified?", "What did the abdominal ultrasound reveal regarding adrenal size, hydronephrosis, distal ureter dilation, or bowel wall abnormalities?", "What were the key findings from genetic testing of the CYP11A1 and STAR genes?", "What trends were observed in the most recent follow‑up endocrine laboratory tests?"], "ground_truth_arguments": ["echocardiography revealed a patent ductus arteriosus", "Bilateral grade 3 vesicoureteral reflux ( VUR ) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically", "Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17 - alpha - hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype.", "Laboratory investigations revealed a slightly decreased sodium level ( 132 mmol / L ) but normal potassium ( 4.8 mEq / L ) and glucose ( 86 mg / dL ) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol ( 1.0 μg / dL ) and markedly elevated adrenocorticotropic hormone ( ACTH ) ( 16,064 pg / mL ) levels were noted. The patient 's cortisol levels did not respond to stimulation with ACTH ( 125 μg ) ( Table 1 ). Meanwhile, he presented a normal 17 - hydroxyprogesterone level ( 0.42 ng / mL ). Plasma renin activity and aldosterone levels were 7.28 ng / mL / hr ( normal range, 1.0–6.5 ng / mL / hr ) and 0.1 ng / dL ( normal range, 3–35 ng / dL ), respectively", "The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening", "no pathogenic variants were detected in CYP11A1 genes. The exome - sequencing results revealed compound heterozygous mutations for c.653C > T and c.661G > A ( p. Gly221Ser ) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively", "Laboratory tests revealed normal levels of cortisol ( 4.6 μg / dL ), sodium ( 139 mmol / L ), potassium ( 4.9 mEq / L ), glucose ( 70 mg / dL ), and ACTH ( 53.6 pg / mL )"]}
{"id": "CaseReportBench:train-417", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}", "questions": ["At what gestational age was the patient evaluated, and which obstetric complication(s) were present at that time?", "What pain symptom(s) did the patient report on initial examination?"], "ground_truth_arguments": ["8th week of gestation, due to initial spontaneous abortion, abdominal pain", "8th week of gestation, due to initial spontaneous abortion, abdominal pain,"]}
{"id": "CaseReportBench:train-592", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case 2': \"Four days after the development of fever, cough, and rhinorrhea, a 6-month-old, previously healthy girl was admitted with generalized tonic-clonic seizure and mental change, as well as increased rigidity of the extremities. CT images of the brain, obtained at another hospital, depicted symmetric low-density lesions in the thalami and external capsules. Two months earlier, the patient's elder sister had died of acute encephalopathy. Conventional brain MR imaging performed on the second day of hospitalization indicated that symmetric T1- and T2-prolonged areas were present in the thalami and external capsules. T2*-weighted gradient-echo images clearly showed that within the thalamic lesions, acute hemorrhage had occurred. After the intravenous administration of gadolinium-diethylene triamine penta-acetic acid, the lesions showed no abnormal enhancement and ADC mapping revealed areas of low signal intensity within them ( Fig. 2A ). Localized proton MR spectroscopy using a stimulated echo-acquisition mode sequence (TR/TE=3000/30, 96 acquisitions, volume of interest=7 mL) showed a small doublet at 1.33 ppm ( Fig. 2B ). Laboratory findings indicated slightly increased levels of serum aspartate aminotransferase, lactate, and ammonia, though the lactate level rapidly returned to normal. CSF analysis revealed increased protein content without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for DNA of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA. The patient was thought to be suffering from acute necrotizing encephalopathy, and was treated with mannitol, acyclovir, and steroid. Her mental state improved and on the second day of hospitalization her level of alertness was almost normal. The extremities gradually became less rigid, and follow-up brain MR imaging and MR spectroscopy performed one week later revealed marked improvement of the initial lesions and disappearance of the doublet at 1.33 ppm ( Fig. 2C ).\", 'Case 1': 'Two days after the onset of fever, vomiting, and diarrhea, a 10-month-old previously healthy boy was admitted with generalized tonic-clonic seizure. Brain CT, performed elsewhere, revealed the presence of symmetric low-density thalamic lesions. On admission, he was drowsy and showed decerebrate rigidity, without focal neurologic signs. Conventional brain MR images obtained using a 1.5-T system on the second day of hospitalization depicted symmetric distribution of T1- and T2-prolonged areas in the thalami ( Fig. 1A ), tegmentum of the pons, and periventricular white matter. T2*-weighted gradient-echo images (TR/TE = 800/30, flip angle = 20°) demonstrated low signal intensities within the thalamic lesions, suggesting acute hemorrhage ( Fig. 1B ). After the intravenous administration of gadolinium-diethylene triamine penta-acetic acid, the lesions showed no abnormal enhancement. Diffusion-weighted MR imaging (b value=1000 sec/mm 2 ) demonstrated high signal intensity in all the lesions, though this was absent in the central portion of thalamic lesions, and other than in this same area, apparent diffusion coefficient (ADC) mapping revealed low signal intensity ( Fig. 1C ). Localized proton MR spectroscopy of the thalami using a stimulated echo-acquisition mode sequence (TR/TE=3000/30, 96 acquisitions, volume of interest=7 mL) showed that compared with an age-matched control subject, peak intensities were higher, occurring at 2.0-2.5 and 0.8-1.5 ppm ( Figs. 1D, E ). Laboratory findings on admission showed increased serum aspartate and alanine aminotransferase levels, though those of blood ammonium and lactate were normal. Cerebrospinal fluid (CSF) analysis showed slightly increased protein content, without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for deoxynucleic acid (DNA) of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA, which would indicate mitochondrial encephalopathy with lactic acidosis and stroke-like episode (MELAS) syndrome. The patient was treated with acyclovir, an antiviral agent, and steroid. His mental state improved, and on the fourth day of hospitalization he was almost alert. Cognitive functions gradually improved, though severe motor deficits remained. Follow-up brain MR imaging performed three months later revealed residual atrophic change in the previously observed lesions; both T1- and T2-weighted images depicted small areas of high signal intensity at the center of the thalami, indicating residual subacute hemorrhage.'}", "questions": ["What low‑density lesions were identified on CT, and in which brain regions were they located?", "Describe the MRI signal characteristics of the lesions (T1, T2, T2* gradient‑echo, diffusion, ADC) and indicate whether gadolinium enhancement was present.", "What abnormalities were reported on localized proton MR spectroscopy for each patient?", "Which serum laboratory values were reported as abnormal (e.g., AST, ALT, lactate, ammonia) in each case?", "What were the cerebrospinal fluid (CSF) findings regarding protein concentration and the presence or absence of pleocytosis?", "What were the results of PCR testing on CSF and peripheral blood for herpes simplex virus, enterovirus, and major mitochondrial DNA mutations?", "Describe the chronic or residual imaging findings reported on the final follow‑up MRI (performed months after admission) and the interpretation of those findings."], "ground_truth_arguments": ["symmetric low - density lesions in the thalami and external capsules", "symmetric T1- and T2 - prolonged areas were present in the thalami and external capsules. T2 * -weighted gradient - echo images clearly showed that within the thalamic lesions, acute hemorrhage had occurred. After the intravenous administration of gadolinium - diethylene triamine penta - acetic acid, the lesions showed no abnormal enhancement and ADC mapping revealed areas of low signal intensity within them ( Fig. 2A ). Localized proton MR spectroscopy using a stimulated echo - acquisition mode sequence ( TR / TE=3000/30, 96 acquisitions, volume of interest=7 mL ) showed a small doublet at 1.33 ppm ( Fig. 2B ). Laboratory findings indicated slightly increased levels of serum aspartate aminotransferase, lactate, and ammonia, though the lactate level rapidly returned to normal. CSF analysis revealed increased protein content without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for DNA of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA.", "symmetric low - density thalamic lesions", "symmetric distribution of T1- and T2 - prolonged areas in the thalami ( Fig. 1A ), tegmentum of the pons, and periventricular white matter. T2 * -weighted gradient - echo images ( TR / TE = 800/30, flip angle = 20 ° ) demonstrated low signal intensities within the thalamic lesions, suggesting acute hemorrhage ( Fig. 1B ). After the intravenous administration of gadolinium - diethylene triamine penta - acetic acid, the lesions showed no abnormal enhancement. Diffusion - weighted MR imaging ( b value=1000 sec / mm 2 ) demonstrated high signal intensity in all the lesions, though this was absent in the central portion of thalamic lesions, and other than in this same area, apparent diffusion coefficient ( ADC ) mapping revealed low signal intensity ( Fig. 1C ). Localized proton MR spectroscopy of the thalami using a stimulated echo - acquisition mode sequence ( TR / TE=3000/30, 96 acquisitions, volume of interest=7 mL ) showed that compared with an age - matched control subject, peak intensities were higher, occurring at 2.0 - 2.5 and 0.8 - 1.5 ppm ( Figs. 1D, E ). Laboratory findings on admission showed increased serum aspartate and alanine aminotransferase levels, though those of blood ammonium and lactate were normal. Cerebrospinal fluid ( CSF ) analysis showed slightly increased protein content, without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for deoxynucleic acid ( DNA ) of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA", "residual atrophic change in the previously observed lesions; both T1- and T2 - weighted images depicted small areas of high signal intensity at the center of the thalami, indicating residual subacute hemorrhage. ' }"]}
{"id": "CaseReportBench:train-537", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["What ocular and neck muscle abnormalities are described, and at what ages did each symptom first appear?", "What family medical conditions are reported, and which relatives are affected?", "Describe the circumstances of the patient's hospital admission, focusing on the nature of the respiratory dysfunction and any identified underlying causes.", "Provide the patient's demographic information (age, gender, ethnicity) and the primary diagnosis that led to admission for hypercapnic respiratory insufficiency."], "ground_truth_arguments": ["with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y.", "The family history was positive for diabetes ( grandmother from the mother ’s side ) and cardiac abnormalities ( mother )", "admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency.", "He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y."]}
{"id": "CaseReportBench:train-372", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': \"An 11-month-old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full-term by Cesarean section and was the second child of the nonconsanguineous parents. The patient's older sibling was phenotypically female, but died in infancy without a clear diagnosis. Although the karyotype was 46, XY, the patient was raised as female gender since she had female external genitalia. In addition, hyponatremia and an elevated adrenocorticotropic hormone (ACTH) level were detected by tests. The blood pressure at clinic was 80/50 mm Hg. Laboratory analysis revealed that the baby had a mildly elevated cholesterol level of 5.72 mmol/L (normal: 2.85–5.70 mmol/L), but a normal triglyceride level. Her plasma sodium level was 131.7 mmol/L (normal: 135–145 mmol/L) with potassium concentration of 6.61 mmol/L (normal: 3.5–5.5 mmol/L). ACTH was >1250 pg/mL (0–46 pg/mL) with a morning cortisol of 1.23 μg/dL (normal: 4–22 μg/dL). Baseline sex hormone tests revealed luteinizing hormone <0.10 U/L, follicle stimulating hormone 1.78 U/L, testosterone 2.50 ng/dL, progesterone 0.44 ng/dL, estradiol 22.99 pg/mL, and dehydroepiandrosterone (DHEA) sulfate <0.1 μg/dL. Adrenal computed tomography (CT) scan revealed enlarged adrenal glands. Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular-like tissues were detected in the bilateral inguinal regions (left: 0.6 × 0.4 cm; right: 0.7 × 0.4 cm) by ultrasonography. Plasma renin activity (PRA) was 0.11 ng/mL per h (normal: 0.93–6.56 ng/mL per h) with a normal aldosterone level of 8.84 ng/dL (normal: 6.5–29.6 ng/dL). Given ambiguous genitalia, karyotype of 46, XY and decreased DHEA and testosterone levels, the diagnosis of 21-hydroxylase deficiency and 11 beta hydroxylase deficiency were excluded. Lacking hypertension and hypopotassemia, the clinical presentation of salt loss and decreased progesterone also did not support the diagnosis of 17OHD. Without an elevated progesterone level, cytochrome PORD was less considered. The differential diagnosis included 3β-HSD deficiency and LCAH. After the informed consent form was signed by the families and approved by the Institutional Review Board of Peking Union Medical College Hospital, further genetic analysis with gene sequencing indicated it is not defective HSD3B2 (related to 3β-HSD deficiency). However, a homozygous variant c.707_708delins CTT (p.Lys236Thrfs∗47) was found on exon 6 of the STAR gene. A truncated disease-causing protein was predicted with MutationTaster software. The variant mutation was found to cause a frameshift at codon 236 with a stop at codon 282. Both parents were found to be heterozygous for the variant (c.707_708delins CTT, p.Lys236Thrfs∗47) at the same locus of the STAR gene without phenotypic consequences. To further evaluate the family pedigree for mutation carriers, the patient's paternal and maternal grandparents also took part in the gene sequencing. The patient's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes (such as mild amenorrhea in women) were recorded, and there were no abnormalities in physical and laboratory examinations. The results of the patient, her parents, and paternal grandfather and maternal grandmother are shown in Fig. 1 . The genogram of LCAH in this family is presented in Fig. 2 . The patient was prescribed hydrocortisone 10 to 12 mg/m 2 and 9α-fludrocortisone 100 μg/d. Gradually, her skin hyperpigmentation and vomiting disappeared, and she had normal growth and development without adrenal crisis attacks. Her hormone and electrolyte levels remained normal, except for a persistently elevated ACTH level throughout 2 years of follow-up. At follow-up for 2 years, the patient is now 104.5 cm tall and weighs 23.3 kg at the age of 4 years old. Her plasma sodium level is 138 mmol/L with a normal potassium concentration of 4.8 mmol/L. Her ACTH level is still elevated (1176 pg/mL). Her baseline sex hormone levels are testosterone <0.1 ng/dL and progesterone <0.08 ng/dL. The level of PRA (1.06 ng/mL per h) is within normal range.\", 'Patient concerns:': 'A case was reported that an 11-month-old Chinese girl who presented with a sex development disorder and hyponatremia. The clinical and genetic tests were carried out to confirm the diagnosis. The genogram of this case was also explored and analyzed. The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular-like tissue in the bilateral inguinal regions were detected with abdominal ultrasound. She was suspected of having LCAH, and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT (p.Lys236Thrfs∗47) on exon 6 of the STAR gene.'}", "questions": ["What are the patient’s age, sex assigned at birth, primary clinical manifestations, and the healthcare setting where they were evaluated?", "Describe the patient’s birth details, the relationship between the parents (e.g., consanguinity), and any information about siblings, including their sex phenotype and outcomes.", "What zygosity was reported for each parent regarding the pathogenic allele (heterozygous or homozygous)?", "Which grandparents were reported to carry the pathogenic allele, and what was their carrier status?", "Did any family members exhibit subclinical phenotypes, physical abnormalities, or laboratory abnormalities?", "How is the case summarized in terms of disorder of sex development and the associated electrolyte disturbance (e.g., hyponatremia)?"], "ground_truth_arguments": ["An 11 - month - old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full - term by Cesarean section and was the second child of the nonconsanguineous parents. The patient 's older sibling was phenotypically female, but died in infancy without a clear diagnosis", "Both parents were found to be heterozygous for the variant", "patient 's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes ( such as mild amenorrhea in women ) were recorded, and there were no abnormalities in physical and laboratory examinations", "A case was reported that an 11 - month - old Chinese girl who presented with a sex development disorder and hyponatremia"]}
{"id": "CaseReportBench:train-153", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory. Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE. Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium. The patient is being followed up and has been specifically instructed to report if she becomes pregnant.'}", "questions": ["What findings were observed on examination of the hard palate mucosa?", "What abnormalities, if any, were identified during the ocular examination?"], "ground_truth_arguments": ["mucosa over the hard palate showed small, firm, yellowish - white plaques", "Ocular examination did not reveal any abnormality"]}
{"id": "CaseReportBench:train-525", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Diagnoses:': 'Ultimately, the patient was diagnosed with argininemia with homozygous mutation (c.32T>C) of the ARG1 gene at 10 years old. Blood tests showed mildly elevated blood ammonia and creatine kinase, and persistently elevated bilirubin.', 'Case report': \"The patient was born at 36 +4 weeks’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness. At this time, his height and weight were 86 cm and 12.5 kg, respectively (both were below the 3rd percentile, according to China's 1995 urban 0–18 year-old male height percentiles scale). A neurologic examination focusing on the motor and sensory nervous system and cerebellar function produced unremarkable findings. Laboratory tests revealed retardation of bone age (equivalent to a 1 year old) and mildly elevated total bilirubin (29.4 μmol/L, normal range: 2–24 μmol/L), direct bilirubin (10.4 μmol/L, normal range: 0–7 μmol/L), and indirect bilirubin levels (18.6 μmol/L, normal range: 1.7–17 μmol/L) but normal hepatic enzyme levels. Blood glucose was slightly lower than normal (3.52 mmol/L, normal range: 3.9–6), whereas his electrolytes were normal. Screening tests for hepatitis B and A were negative. A growth hormone excitement test revealed low levels of growth hormone (0 minute: 0.76 ng/mL; 30 minutes: 4.5 ng/mL; 60 minutes: 6.3 ng/mL; 90 minutes: 4.1 ng/mL; and 120 minutes: 1.5 ng/mL). An MRI revealed a normal pituitary gland, and thyroid function was normal. The boy was diagnosed with PGHD and managed accordingly, being treated with growth hormone for about 1 month. No treatment effect was evident. However, he received no follow-up until 10 years of age. At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance. At this time, his height and weight were still below the 3rd percentile, at 116 cm and 20.1 kg, respectively. He exhibited no organomegaly. His muscle strength of the low extremities was grade 4 (Oxford Scale), and he showed increased distal muscle tone than normal, hyper-reflexia, and a negative Babinski sign. Laboratory tests revealed mildly elevated hepatic enzyme levels, including aspartate transaminase (50.9 IU/L, normal range: 0–50 IU/L) and alanine transaminase (52 IU/L, normal range: 0–45 IU/L), as well as mildly elevated total bilirubin (47.7 μmol/L, normal range: 0–25 μmol/L), direct bilirubin (16.4 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (31.3 μmol/L, normal range: 0–25 μmol/L). His creatine kinase (564.4 IU/L, normal range: 55–190 IU/L) and blood ammonia levels (62.3 mmol/L, normal range: 9–30 mmol/L) were slightly elevated. A urine occult blood test was positive (++). Red blood cells (3–4/HP, normal range: 0–3/HP) were evident in a urine sediment microscopy. Both renal ultrasound and renal function were normal, as were the results of cranial MRI and electroencephalography. A peripheral nerve examination revealed reduced compound muscle action potential (CMAP) of the right peroneal nerve and bilateral tibial nerve, while the right peroneal nerve distal latency was suspected to be prolonged. A muscle biopsy revealed neurogenic lesion (Fig. 1 ). A gene test was performed and the results demonstrated that he carried compound homozygote mutations of ARG1 (c.32T > C) (Fig. 2 ). Lee et al and Wu et al reported the mutation, which can lead to argininemia, in South Korea and Chinese populations in 2011 and 2015. Subsequently, his blood and urine amino acid levels were analyzed, revealing a blood arginine concentration of 108.42 μM (normal range: 10–50 μM) as well as elevated urinary excretion of orotic acid; however, his blood citrulline, glutamine, glutamate, and alanine concentrations were normal. His intelligence quotient was lower than normal, at 80. The boy subsequently diagnosed with argininemia. Following the diagnosis, we recommended that the patient begins a low-protein diet (0.8 g/kg/day) to decrease his blood arginine levels, as well as start taking citrulline (150–200 mg/kg/day). His mental state and vomiting had clearly improved after 3 months of this treatment. Laboratory tests conducted again at a local hospital which the following values were obtained (note that the normal ranges used at this hospital slightly differ from those used at our hospital): aspartate transaminase (45 IU/L, normal range: 0–37 IU/L), alanine transaminase (46.1 IU/L, normal range: 0–40 IU/L), total bilirubin (31.9 μmol/L, normal range: 3.4–20.5 μmol/L), direct bilirubin (14.3 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (17.6 μmol/L, normal range: 0–18 μmol/L). His urine occult blood test was positive (+). No red blood cells were evident in his urine sediment microscopy. After 9 months treatment, his height and weight reached 121 cm and 22 kg, but his spastic diplegia symptoms had not improved.\", 'Patient concerns:': 'A Chinese boy initially presented with severe stunting and partial growth hormone deficiency (PGHD) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later (at 10 years old), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy.'}", "questions": ["Describe the patient's birth circumstances, including gestational age, birth weight, and any immediate neonatal complications.", "Summarize the patient's early developmental milestones and any delays observed before and after the first year of life.", "What is the family medical history and the health status of the patient's siblings?", "Outline the patient's early dietary preferences, aversions, and related symptoms such as vomiting.", "At what age did the patient first present with growth concerns, and what were the key findings regarding stature, weight, and growth‑hormone assessment?", "What treatment was initiated for the identified growth‑hormone deficiency, and what effect was observed?", "Provide a summary of the neurological and cognitive symptoms that emerged around age ten, including seizures, gait disturbances, motor limitations, and academic performance.", "List the long‑term complications reported in the patient after the later neurological presentation."], "ground_truth_arguments": ["The patient was born at 36 +4 weeks ’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness", "At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance", "A Chinese boy initially presented with severe stunting and partial growth hormone deficiency ( PGHD ) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later ( at 10 years old ), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy."]}
{"id": "CaseReportBench:train-109", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumor was made; biopsy was deferred and hormonal treatment was modified. A 9-year-old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour. The cortisol level was low, and levels of 17 alpha-hydroxyprogesterone, plasma corticotrophin (ACTH), and testosterone were high. Scrotal ultrasound revealed well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses with posterior acoustic shadowing in both testes, in the medial aspects near the mediastinum testis. The right testicular mass measured 1.3×1.1 cm, and the left testicular mass measured 1.5×1.2cm ( Figures 1, 2 ). On colour Doppler, the masses had minimal internal vascularity ( Figure 3 ). The rest of the testes showed normal flow. The epididymis and cord structures were normal. There was no evidence of hydrocoele on both sides. Testicular tumor markers were negative. Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement ( Figure 4 ). In a patient with CAH and bilateral testicular masses that had a typical sonographic appearance, a diagnosis of testicular adrenal rest tumor was made, and biopsy was deferred. Hormonal treatment was intensified, and the testicular masses are followed up. The patient improved clinically, which was associated with a decrease in testosterone and 17 alpha-hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months. Currently, the patient is advised to undergo follow-up ultrasound examinations every 3 months.'}", "questions": ["What demographic information about the patient is provided in the case report?", "What information is provided regarding the timing and circumstances of the patient's diagnosis of congenital adrenal hyperplasia?", "What factors are mentioned as influencing the control of the patient's condition?", "What physical or behavioral findings are reported for the patient?"], "ground_truth_arguments": ["A 9 - year - old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour"]}
{"id": "CaseReportBench:train-367", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'CASE REPORT': \"A 27-year-old male, presented to our clinic with a history of foreign body sensation in both eyes for the previous 2 years. He had a history of blistering skin lesions on the photo-exposed areas of the body for the past 12 years. At first, blisters started developing over the lower extremities and then gradually involved upper extremities and face. There was also a history of hyper-pigmentation and scarring of the photo-exposed areas of the body. He developed severe pain in the fingers of both hands 1-year prior presentation. He complained of the passage of red colored urine for the past 1 year. There was no history of acute abdominal pain and no family history of the similar phenomenon was found. Striking features on physical examination were a pinched up nose, scarring over the lips, nose, hands, and resorption of distal phalanges of all the fingers in both hands except onycholysis of the smallest digits. Onycholysis was present on all the toes. The remainder of the systemic examination was noncontributory. The patient's uncorrected visual acuity was 20/40 in both eyes. Best corrected visual acuity was 20/20 in both eyes with a correction of –0.5 × 115° in the right eye and –1.25 × 80° in the left eye. Air-puff tonometry measured intraocular pressure of 14 mm-Hg bilaterally. The fundus examination was unremarkable. Slit-lamp examination indicated scleral necrosis in the interpalpebral area of both eyes that was more pronounced temporally compared to nasally. Temporally, it was 4 mm × 3 mm in the left eye and 3 mm × 3 mm in the right eye. Nasally, minimal scleral necrosis was seen with overlying fibrosed conjunctiva in both eyes. Mild conjunctival scarring was present in the temporal necrosed part of the right eye. In the left eye, the temporal necrosed part was devoid of conjunctival tissue, a frill of conjunctival tissue was present at the margin of the necrosed area. Conjunctiva and sclera in the covered area appeared to be normal. Infiltrations were seen in the peripheral cornea of both eyes near the limbus with temporal and nasal involvement. Fluorescein staining indicated normal epithelium. Schirmer's test 1 was 8 mm in the right eye and 10 mm in the left eye. These symptoms were suggestive of porphyria. Laboratory testing based on the definite pattern of accumulation and hyperexcretion of porphyrins and porphyrin precursor is the most effective measure for diagnosis and typing of porphyrias. Exact porphyrin isomer identification requires sophisticated equipment such as high-performance liquid chromatography which is unavailable at our center and in most hospitals in the developing countries. Hematological tests reported hemoglobin, 9.8 g/dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase (423U/l) and mild increase in serum bilirubin (1.8 mg/dL). Ultrasonography of the whole abdomen showed splenomegaly (17 mm). These features are suggestive of hemolytic anemia. The treatment involved complete avoidance of sunlight and use of dark goggles. The patient was prescribed topical cyclosporine 0.5% eye drop 3 times a day and ocular lubricant was prescribed for both eyes. We planned a full-thickness scleral patch graft with amniotic membrane transplant in the necrosed region. The patient was advised to return for periodic follow-up to our cornea clinic.\"}", "questions": ["What urinary discoloration did the patient report and for how long?", "What abnormalities were noted in the patient's hematologic profile and related laboratory tests?", "What did the abdominal ultrasound indicate about the spleen?"], "ground_truth_arguments": ["red colored urine for the past 1 year.", "hemoglobin, 9.8 g / dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase ( 423U / l ) and mild increase in serum bilirubin ( 1.8 mg / dL )", "splenomegaly ( 17 mm )"]}
{"id": "CaseReportBench:train-443", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 32-year-old female (gravida 4 para 3) presented to her obstetrician with her next pregnancy following the birth of a previous female child with classical congenital adrenal hyperplasia (CAH). The estimated fetal age was 15 weeks and 4 days at the time of presentation based on initial sonographic assessments. At 19.42 gestational weeks (GWs), ultrasound revealed genitalia that were female-appearing but ambiguous or atypical. A karyotype indicated the fetus was 46,XX with no chromosomal abnormalities. CYP21A2 gene testing of DNA from amniotic fluid showed compound heterozygosity for an R356W mutation on one allele and a 30-kb deletion on the other allele, confirming a prenatal diagnosis of CAH due to 21-hydroxylase deficiency. Parental genetic testing confirmed the fetal genotype. The mother subsequently underwent multiple consultative and care appointments on a bi-weekly/monthly basis with endocrinology, genetic counseling, psychology, urology, and perinatology until delivery at the Fetal Maternal Center, and followed at our CAH Comprehensive Care Center. 1 This next pregnancy led to the surfacing of psychological issues for the proband sibling with regards to her external genitalia, and the related challenges the family experienced during her first year of life, prior to the establishment of our center. It was imperative to immediately address and resolve these issues for both the proband sibling and the family, prior to the arrival of the next affected female child, so that the experience for all family members would be much improved via therapy, education, and a supported effort by the care provider team for CAH. At 29.14 GW, high-resolution prenatal ultrasound (General Electric, 5-9 MHz transducer) was performed and three serial 2D measurements of the biparietal diameter (71.1 mm; 20th percentile) of the fetus and two serial 2D measurements of the head circumference (258.1 mm; 3rd percentile) were averaged and compared with standard references using the Hadlock growth curves. 2 At 30.57 GW, fetal magnetic resonance imaging (MRI; Philips 1.5T) was performed to better evaluate clinically for other abnormalities as MRI can provide information regarding certain conditions like white matter abnormalities and temporal lobe atrophy that cannot be obtained by ultrasound alone. 3 2-D and 3-D MRI measurements of fetal brain structures were computed ( Figure 1 ) and shown in Table 1 . 2-D measurements of brain biparietal diameter, occipitofrontal diameter, skull biparietal diameter, and occipitofrontal diameter, and calculated head circumference were recorded. 4 Significant deficits were noted for skull biparietal diameter and occipitofrontal diameter versus age-matched controls ( Figure 2 ). 5, 6 Absolute biparietal diameter measurements were similar for ultrasound and MRI. 3-D measurements were obtained of the extra-axial cerebrospinal fluid (CSF) volume, supratentorial volume, cerebellar volume, cortical plate volume, and total lateral ventricles volume ( Figure 3 ). 4 Total intracranial volume and deep gray matter volume, but not developing white matter, showed deficits versus controls ( Table 1 ). 5 - 7 A postnatal follow-up MRI of the patient on day 10 of life showed a total brain volume (300.82 cm 3 ) that was below the 5th percentile for age-matched, healthy infants. 8 The neonate was born at 39.14 GW, via uncomplicated vaginal delivery, and seen in the CAH clinic 3 days after birth. On physical examination, she was Prader stage 3, with clitoral width 1 cm, stretched clitoral length 1 cm, and noticeable hyperpigmentation and rugation of the labioscrotal folds. Her examination was otherwise unremarkable. She was a well-appearing neonate with no concerns for adrenal crisis. Hormone analytes were measured at the visit, prior to initiation of treatment, and included: 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone (LC-MS/MS for all; Quest Nichols Diagnostic Laboratory, San Juan Capistrano, CA). The neonate had an elevated serum 17-OHP of 11,500 ng/dL (normal range for term newborns within 12 h of birth: ≤460 ng/dL), androstenedione 4917 ng/dL (normal range not established for newborns; normal range for infants: 6–78 ng/dL), and testosterone 279 ng/dL (normal range of females 1–10 days old: ≤24 ng/dL).'}", "questions": ["What category of prenatal diagnosis was made based on genetic testing?", "What type of enzyme deficiency was implicated in the diagnosed condition?", "What genetic findings supported the prenatal diagnosis?"], "ground_truth_arguments": ["prenatal diagnosis of CAH due to 21 - hydroxylase deficiency"]}
{"id": "CaseReportBench:train-142", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'CASE DESCRIPTION': \"A 41-yr-old man was referred to our emergency room from a local clinic on July 3, 2006, with the impression of acute viral hepatitis due to a remarkable elevation of liver enzymes. He had experienced generalized weakness, dark urine, and jaundice for a two week period. His previous history included community-acquired pneumonia and carpal tunnel syndrome, but neither diabetes mellitus nor hypertension. He complained of impotence, and his mother described precocious puberty and hirsutism beginning at the age of 7. He was not married and had no children. His vital signs were a blood pressure of 115/92 mmHg, a regular pulse of 105/min, and a respiratory rate of 18/min. His height was 152.5 cm (< 3th percentile) and body weight was 72.5 kg. The body mass index was 32.5. Acanthosis nigricans was present in both axillae, and there was central obesity with erythematous, scaly, guttate papules on the lower abdominal skin. He also had a rather ambiguous buffalo hump; however, moon face or red stria was not present ( Fig. 1 ). Total and direct bilirubin levels were elevated at 11.6 mg/dL and 8.6 mg/dL, respectively. The AST and ALT levels were 224 and 1,044 U/L, respectively. Serum BUN level was 9.7 mg/dL, and serum creatinine level was 0.82 mg/dL. Serum electrolytes were normal. Based on a positive anti-HAV IgM titer, he was diagnosed with acute hepatitis A. During the evaluation to exclude other causes of liver dysfunction, a 4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT ( Fig. 2A, B ). We evaluated the endocrine function ( Table 1 ). Twenty-four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements (226.4 µg/24 hr; 122.1 µg/24 hr). Plasma cortisol was within the normal range (7.4 µg/dL), however, ACTH level was very high (676.5 pg/mL). Urine 17-OHCS and 17-ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated (0.414 ng/mL). DHEA-S was within the normal range (1.88 µg/mL). Based on the high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass, we suspected a pituitary corticotrophic adenoma with marked asymmetric adrenal hyperplasia. To confirm the diagnosis of Cushing's syndrome, low- and high-dose dexamethasone suppression tests were performed. Then, 24-hr urine cortisol was markedly suppressed, not only by high-dose dexamethasone but also by low-dose dexamethasone ( Table 2 ); this result essentially eliminates the diagnosis of Cushing's syndrome ( 7, 8 ). We thus suspected CAH based on the short stature, precocious pubarche and marked suppression of 24-hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH. The testosterone level was normal (3.51 ng/mL), but 17α-hydroxyprogesterone (17-OHP) was markedly elevated to 30,000 ng/dL, strongly supporting the diagnosis of a simple virilizing form of CAH. Gene analysis revealed CAH due to 21-hydroxylase deficiency by a compound heterozygote for CYP21 mutations: Ile173Asn (I173N) and Arg357Trp (R357W) ( Fig. 3 ), confirming the diagnosis of a simple virilizing from of CAH due to mutations in CYP21 . We began administration of adrenal steroids. After 6 months of treatment with dexamethasone (0.25 mg daily), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig. 2C, D ). 17-OHP and ACTH levels were normalized to 118 ng/dL and 20.8 pg/mL, respectively, and impotence was improved.\", 'Mutation analysis': \"Genomic DNA was extracted from the peripheral blood leukocytes of patient by using the Wizard Genomic DNA Purification Kit according to the manufacturer's instructions (Promega, Madison, WI, USA). All exons of the CYP21 gene were amplified by PCR on a thermal cycler (Applied Biosystems, Foster City, CA, USA). Direct sequencing was performed using the BigDye Terminator Cycle Sequencing Ready Reaction kit and an ABI Prism 3130 Genetic Analyzer (Applied Biosystems). The sequences were analyzed using the Sequencer program (Gene Codes Corp., Ann Arbor, MI, USA) and were compared to the reference sequences. The numbering of nucleotide positions was done according to the CYP21 DNA sequence, and the Gen-Bank accession number was NM000500.\", 'Biochemical assays': 'Blood samples were obtained in the morning after an overnight fast and a 30-min resting period in the supine position. Hormones were assayed using IRMA kits. For low- or high-dose dexamethasone suppression test, 0.5 or 2 mg dexamethasone was administered 4 times a day for 2 consecutive days.'}", "questions": ["Describe any hirsutism observed during the patient's physical examination.", "What evidence of acanthosis nigricans was noted?", "Detail the characteristics of any erythematous, scaly, guttate papules found on the patient's skin.", "What Cushingoid features were reported?"], "ground_truth_arguments": ["hirsutism", "Acanthosis nigricans was present in both axillae", "erythematous, scaly, guttate papules on the lower abdominal skin", "rather ambiguous buffalo hump; however, moon face or red stria was not present"]}
{"id": "CaseReportBench:train-252", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'This boy was born to nonconsanguineous Chinese parents. He was born at term, weighed 3100 g with good Apgar scores. He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia. He was brachycephalic with hypopigmented hair. He had poor weight gain with swallowing dysfunction and significant reflux disease requiring gastrostomy feeding. He started having orofacial and limb dyskinesias at 1.5 years of age and subsequently developed refractory multifocal epilepsy at 3 years of age requiring multiple antiepileptics and ketogenic diet to control his seizures. Electroencephalogram showed focal and diffuse slowing consistent with background encephalopathic state, with frequent multifocal epileptiform discharges bilaterally. He developed central and obstructive sleep apneas at 3.5 years of age and was initiated on night bilevel positive airway pressure. He was evaluated with magnetic resonance imaging brain scan and chromosomal microarray at 8 months of age, which was normal. Whole-exome sequencing and direct sequencing confirmed that he harbored compound heterozygous missense mutations c.3130C>T (p.Arg1044Cys), c.3430C>T (p.Arg1144Cys), and c.4078G>A (p.Ala1360Thr) in the LRPPRC gene mapped to chromosome 2p21-p16. Parents were carriers of the mutation. His muscle biopsy showed normal muscle architecture with no “ragged-red” fibers, necrotic fibers, or regenerating fibers seen. Cytochrome c-oxidase was positive in most of the fibers. There were no light microscopic or ultrastructural features to support mitochondrial myopathy. Respiratory chain enzymes in skeletal muscle were diagnostic for complex IV defect ( Table 1 ). He is currently 5 years of age, has generalized dystonia, and is mainly chair-bound. He has intermittent eye contact and minimal vocalization. His baseline lactates ranged from 1.5 to 3.6 mmol/L with mild intermittent metabolic acidosis. However, there were no episodes of acute ketosis, glycemic derangements, or any acute stroke-like episodes. The parents’ first child was diagnosed with steroid-resistant nephrotic syndrome at 18 months of age requiring tacrolimus treatment. Their second pregnancy was terminated at 22 weeks’ gestation due to antenatal diagnosis of Ebstein’s anomaly and multiple valvular abnormalities.'}", "questions": ["Describe the patient's birth circumstances, parental relationship, birth weight, Apgar scores, and early developmental signs such as head lag and hypotonia.", "What feeding and growth problems did the patient experience, including weight gain, swallowing dysfunction, and reflux disease?", "When did the patient first exhibit orofacial and limb dyskinesias, and when did refractory multifocal epilepsy become apparent?", "Describe the sleep-related breathing disorders the patient experienced and indicate the approximate period when they were first noted.", "What is the carrier status of the parents for the LRPPRC mutations found in the patient?", "What medical conditions have affected the parents' other children, and what were the outcomes of those conditions?"], "ground_truth_arguments": ["This boy was born to nonconsanguineous Chinese parents. He was born at term, weighed 3100 g with good Apgar scores. He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia.", "He had poor weight gain with swallowing dysfunction and significant reflux disease", "He started having orofacial and limb dyskinesias at 1.5 years of age and subsequently developed refractory multifocal epilepsy at 3 years of age", "He developed central and obstructive sleep apneas at 3.5 years of age", "Parents were carriers of the mutation", "The parents ’ first child was diagnosed with steroid - resistant nephrotic syndrome at 18 months of age requiring tacrolimus treatment. Their second pregnancy was terminated at 22 weeks ’ gestation due to antenatal diagnosis of Ebstein ’s anomaly and multiple valvular abnormalities."]}
{"id": "CaseReportBench:train-312", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE REPORT': 'A 5 year-old boy was referred to the Pediatric Dentistry Clinic with the complaint of \"a small ball that appeared in the mouth\". During the anamnesis, the patient was diagnosed as having hypophosphatemic vitamin D-resistant rickets. The child was the third twin; however, the parents as well as the siblings, did not have the metabolic disorder. The medicines taken by the patient were calcitriol and phosphate supplements. He presented short stature and several skeletal abnormalities. Clinical examinations revealed fistula at the periapical region of primary maxillary left lateral incisor without caries or trauma ( Figure 1 ). The patient presented complete primary dentition and none of the teeth examined showed evidence of caries ( Figure 2A-B ). Radiographic examinations included periapical, panoramic and occlusal views showing pulp chambers enlarged, with pulp horns extending to the dentino-enamel junction, poorly defined lamina dura and hypoplastic alveolar ridge ( Figure 2C ). The patient presented a large physiologic wear of the incisors, geographic tongue and primary mandibular right lateral incisor (#82) and canine (#83) with crown alteration ( Figure 3A-B ). There were areas of rarefaction around the apices of the primary maxillary right and left central incisor (#51,61), primary maxillary right and left lateral incisor (#52,62), primary maxillary right and left canine (#53,63) and primary maxillary right and left first molar (#54,64), primary mandibular right and left central incisor (#81,71) ( Figure 4 and 5A-B ). Initially, two sections of management were performed. The treatment was divided into two phases: at first, the extraction of the teeth was performed: #51, 61, 81 and 71. At the second phase, endodontic treatment of the teeth: #52, 62, 53 and 63. These procedures were executed with local anesthesia and rubber dam isolation. The root canals were submitted to preparation with Kerr files and dressing with paramonoclorofenol (Biodinâmica LTDA, Brazil) for 48 hours. Canals were filled with zinc oxid-eugenol and iodoform paste and restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA). During the aforementioned treatment, primary mandibular right first molar (#84), primary maxillary right and left first molar (#54,64) and primary mandibular left second molar (#75) showed periapical fistula without evidence of caries or trauma in a short-term. These teeth were extracted. However, the child was constantly sick and did not attend the consultations. In the other teeth, the primary mandibular right second molar (#85), lateral incisor and canine (#82,83), primary maxillary right and left second molars (#55,65), primary mandibular left first molar and lateral incisor and canine (#74,73,72), the choice of treatment was to open the pulp chambers and make a dressing with formocresol (Biodinâmica LTDA, Brazil). After a 7-day period, the dressing with formocresol was removed and the root instrumentation was performed and filled with zinc oxid-eugenol and iodoform paste, afterwards the teeth were restored with resin glass ionomer cement (Vitremer, 3M/ESPE, USA) ( Figure 6 ). In order to maintain the space of primary maxillary right and left second molars and primary mandibular right second molar, a fixed space-maintainer was made and cemented with resin modified glass ionomer cement (Rely X, 3M/ESPE, USA) ( Figure 7A-B ). The postoperative clinic course was uneventful and after six months of follow-up, the child did not show clinical abscesses.'}", "questions": ["What medication and supplement regimen is reported for the patient in the case description?"], "ground_truth_arguments": ["calcitriol and phosphate supplements"]}
{"id": "CaseReportBench:train-503", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Observation': 'An 18-month-old boy born after an uncomplicated full-term pregnancy was hospitalized for psychomotor regression and drug-resistant myoclonic epilepsy. There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected. The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay. Physical examination revealed a macrocephaly of 51 cm with a dysmorphic syndrome consisting of a frontal bossing and a broadening of the nasal bridge. The neurological examination revealed an axial hypotonia with no further optical problems or responsiveness to light. Ophthalmologic examination showed a cherry-red spot without optic atrophy. Cerebral computed tomography (CT) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter (Fig. 1 ). With magnetic resonance imaging (MRI) the thalamus was hyperintense on T1-weighted images and hypointense on T2-weighted images (Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem. Clinical data and thalamic involvement suggest metabolic diseases such GM2 gangliosidosis (e.g. Tay-Sachs and Sandhoff diseases) or GM1 gangliosidosis (e.g. Landing disease), Canavan disease or Alexander disease. Chromatography of amino acids in the blood, urine and cerebrospinal fluid (CSF) was normal and chromatography of organic acids in the urine was also normal. Enzymatic assays were performed in France and revealed a deficiency of both hexosaminidases A and B confirming the diagnosis of Sandhoff disease.'}", "questions": ["Can you describe the patient's demographic information, prenatal and perinatal background, and the main clinical concerns that led to admission?", "What family history information is mentioned regarding parental relationships and the health of the patient's siblings?", "When did the patient's neurological symptoms begin, and what were the early manifestations?"], "ground_truth_arguments": ["An 18 - month - old boy born after an uncomplicated full - term pregnancy was hospitalized for psychomotor regression and drug - resistant myoclonic epilepsy.", "There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected.", "The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay."]}
{"id": "CaseReportBench:train-326", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case 2': 'An 18-year-old girl was admitted to our hospital following development of generalized tonic-clonic seizure in November 2016. Ten days ago, she was diagnosed with ileus because of abdominal pain as well as constipation in her local hospital. However, the symptoms were not relieved and a series of tests including abdominal X-ray, CT scan, and ultrasound were normal. Her brain MRI was performed in her local hospital indicating PRES (Fig. 3 ). MR angiography showed no abnormality (data not shown). However, the diagnosis was vague and the patient was transferred to the emergency department of our hospital due to seizures. Anticonvulsants including benzodiazepines and oxcarbazepine were used to control the seizures. The recurrent abdominal pain and seizures gave us reason to suspect of AIP, given the prognosis from case 1. She had no family history of similar symptomatology or other particularly notable medical history. At the time of admission, her blood pressure was 136/101 mm Hg, and her heart rate was 109/min. The general physical examination was normal and there was no focal neurological deficit. On the night of admission, the patient had hallucination. Except for remarkable hyponatremia of 104 mmol/L, her serum potassium was 3.0 mmol/L, aspartate transaminase 243 U/L, alanine transaminase 142 U/L, and total bilirubin 37 μmol/L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero-negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid (CSF) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution (Fig. 4 ). AIP was confirmed by 3 repeated urine Watson–Schwartz tests. The patient was given a high carbohydrate diet and intravenous dextrose. No hematin was available for her, but her status improved gradually when she was discharged. No seizures occurred, and her abdominal pain regressed. Two weeks later, a repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions (Fig. 5 ). One month later, she recovered completely and went back to work. No acute attacks have occurred to date. Because this was cases report without any research involving human beings or experimental subjects, the ethical approval was not required in our institute. But patients have provided informed consent for publication of the case.', 'Case presentation:': \"Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson–Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up.\", 'Case 1': 'In December 2014, a 27-year-old man was admitted to our hospital for abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week. He was diagnosed with acute pancreatitis with mild elevated urine amylase in his local hospital. No abnormalities were found in his abdominal computed tomography (CT) and X-ray. However, the paroxysmal pain was not relieved, and his blood pressure increased. Six days later, a generalized tonic-clonic seizure occurred. Then, partial seizures in the left limb continued. He was transferred to our hospital. No particular medical or family history was reported. At the time of admission, he described recurrent severe paroxysmal abdominal and lumbar pain. His clinical examination was unremarkable, except for decreased tendon reflex in the 4 limbs. There was no complaint of visual disturbance. The patient had moderately increased blood pressure (159/101 mm Hg) and tachycardia (112/min). His creatine kinase was 246 U/L (normal, 0–170 U/L), aspartate transaminase was 42 U/L (15–40 U/L) and serum sodium was 130 mmol/L (normal, 137–147 mmol/L). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1-weighted images and were hyperintense on T2-weighted and fluid-attenuated inversion recovery images. Diffusion-weighted images (DWI) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient (ADC) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES (Fig. 1 ). There was mild contrast enhancement (data not shown). Electroencephalography showed diffuse slow waves without epileptiform discharges. The results of the cerebrospinal fluid analysis were normal. His severe recurrent abdominal pain without clear etiology was suspect of AIP. The diagnosis of AIP was made after 3 repeated positive urine Watson–Schwartz tests for porphobilinogen (PBG). His urine turned dark and red upon exposure to light (Fig. 2 ). Glucose infusion and a high carbohydrate diet were given to the patient, as hematin was not available in our hospital. The patient responded well and recovered gradually. He was discharged with no seizure or abdominal pain. Upon review, he remained asymptomatic.'}", "questions": ["What seizure types were observed in the patients, and was there any change in seizure pattern over time?", "What were the findings of the initial brain MRI performed at the local hospital that led to a diagnosis of posterior reversible encephalopathy syndrome (PRES)?", "How did the follow-up brain MRI obtained at your hospital differ from the initial MRI?", "What did the repeat brain MRI performed after recovery show regarding the presence or disappearance of the previously identified lesions?", "Did the neurological examination reveal any focal deficits, and if so, what were they?", "What abnormalities in tendon reflexes were observed during the physical examination?", "Were any neuropsychiatric symptoms such as hallucinations reported by the patients?", "What were the results of the cerebrospinal fluid (CSF) analysis?", "What findings were reported on the electroencephalogram (EEG), particularly regarding background activity and epileptiform discharges?", "Describe the detailed MRI characteristics of the lesions (location, T1/T2/FLAIR signal, DWI/ADC appearance, presence of vasogenic edema, and contrast enhancement) that supported the diagnosis of PRES.", "What was the seizure status of the patients after treatment and at discharge (e.g., occurrence of further seizures)?"], "ground_truth_arguments": ["generalized tonic - clonic seizure", "brain MRI was performed in her local hospital indicating PRES", "seizures", "seizures", "no focal neurological deficit", "hallucination", "The cerebral spinal fluid ( CSF ) analysis was normal", "Brain MRI performed in our hospital 6 days later revealed partial resolution", "No seizures occurred", "repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions", "seizures and PRES on brain magnetic resonance imaging ( MRI", "seizures", "generalized tonic - clonic seizure occurred. Then, partial seizures in the left limb continued", "decreased tendon reflex in the 4 limbs", "Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1 - weighted images and were hyperintense on T2 - weighted and fluid - attenuated inversion recovery images. Diffusion - weighted images ( DWI ) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient ( ADC ) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES ( Fig. 1 ). There was mild contrast enhancement", "Electroencephalography showed diffuse slow waves without epileptiform discharges", "The results of the cerebrospinal fluid analysis were normal"]}
{"id": "CaseReportBench:train-79", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': \"A young stocky built adult patient appearing in early twenties dressed in shirt and pant with a thick moustache and beard accompanied with parents walked inside psychiatry out-patient department (OPD) with a referral from plastic surgery OPD concerning gender affirmation surgery. Patient introduced self in a husky masculine voice as Ms. T, a 21-year old female patient and expressed desire to be named as Mr. T, in further conversation. On interview, parents reported patient to be their eldest daughter born of a non-consanguineous marriage following a full term normal vaginal delivery. Parents reported since early childhood, patient was tomboyish, more comfortable playing with boys, watching wrestling and never showed interest in dolls or playing with younger sister or girls at school. Patient used to wear shirt and skirt to school, but at home used to prefer wearing T-shirt and jeans. From adolescence onwards, patient started to gain weight, developed hirsutism and never attained menarche. Mother had to frequently remove patient's facial hairs by hair removing cream. Patient started to feel attracted towards females though never had any sexual contact. Patient started to develop strong disliking towards self being called as a female, withdrew self from female friends and interest in studies declined; but never verbalised these feelings to anyone. 17 years onwards, after completing high school patient started to express strong resentment. Thereafter, with parents consent patient started to dress as males, stopped removing facial hairs. From 18 years onwards, proclaiming self as Mr. T patient started to work as a salesman. Patient and parents were happy with the new desirable identity. Difficulties faced were using common urinals, feeling ashamed of getting the anatomical sex being disclosed and inability to study further or procure a white collared job because of high school certificate mentioning sex as female. Despite these problems, patient was more comfortable in male gender role and since past 2 years, started seeking help for gender affirmation surgery. Patient appeared to be of average intelligence and had no persistent aggressive, violent or criminal tendencies. There was no past history of taking any hormones exogenously. Examination revealed 65 kg weight, 160 cm height and 116/82 blood pressure. External body habitus was of male and external genitalia was of female. There were no apparent cushingoid features. Karyotyping showed 46XX pattern. Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X-ray were normal. Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17-OH progesterone and dehydro-epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test suggesting diagnosis of non-classical congenital adrenal hyperplasia.\"}", "questions": ["What genetic testing was conducted and what were its findings?", "What overall imaging findings were reported in the case, encompassing ultrasound, MRI, and chest X‑ray results?", "What laboratory investigations were performed and which results were reported as normal or abnormal?"], "ground_truth_arguments": ["Karyotyping showed 46XX pattern", "Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X - ray were normal", "Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17 - OH progesterone and dehydro - epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test"]}
{"id": "CaseReportBench:train-604", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Microbial defects': 'In PLS, neutrophil function test showed reduced response to staphylococcus spp. and Actinobacillus actinomycetemcomitans . There is a hypothesis that herpes viruses together with pathogenic bacteria, including A. actinomycetemcomitans and underlying host defense disorders, participate in the development of PLS periodontitis. Presence of numerous virulence factors such as leukotoxin, collagenase, endotoxin, epitheliotoxins and fibroblast-inhibiting factor, suggests that PLS is mediated bacteriologically and therefore could be treated to some improvement with antibiotics. The serum of the patients showed high immunoglobulin G (IgG) titer against A. actinomycetemcomitans . Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples. Antibiotic therapy was associated with elimination of A. actinomycetemcomitans from the periodontal pockets and serum IgG titers against A. actinomycetemcomitans decreased in the patients.', 'Clinical examination': 'Extra-oral examination On extra-oral examination, patient presented with well-demarcated, yellowish, keratotic plaques over the skin of palms and soles extending on to the dorsal surfaces. Skin of both palms and soles was peeling off leaving underlying red shiny area suggestive of keratoderma. Well circumscribed, psoriasiform, erythematous, scaly plaques were also present on the elbows and knees bilaterally along with dystrophy and transverse grooving of the nails. The fingers were pointed giving clawed appearance. Intra-oral examination Intra-oral examination revealed edentulous area between teeth 44 and 33 and 11, 21 and 22 were also missing. Edentulous maxillary and mandibular ridges were covered with normal mucosa. The teeth present were 12, 13,14,15,16,22, 24, 25, 26, 33, 34, 35, 36, 44, 45 and 46 covered with soft deposits and band of subgingival calculus. Gingiva was fiery red in color with inflammatory gingival enlargement Iva Ingle Classification grade II. Pathological migration was associated with 12, 14, 23, 24, 33 and 34. On assessment grade III mobility was present in relation with 14, grade II in relation with 24, 25, 33, 34, 36 and 44. Remaining teeth were present with grade I mobility. There was the presence of recession grade III in relation with 14 and 33. Extra-oral examination She complained about dry scaly skin of palms and soles like her sister, but she has not taken any dermatological treatment for that. On examination, well-demarcated keratotic plaques over the skin of her palms and soles, extending on to dorsal surfaces were present. Intra-oral examination She showed the presence of 16, 26, 31, 36, 46, 41 and 53 in the oral cavity. There is grade III recession and grade II mobility in 53. Remaining teeth revealed the presence of soft deposits and grade I mobility.', 'Case 2': 'Second patient was a 6-year-old sister of the above patient. She was asymptomatic before 2 years. Her father noticed mobility in relation with some of her deciduous teeth and then early exfoliation of same. Her elder sister had same complain, so he brought her also for a checkup and treatment at Government Dental College and Hospital, Ahmadabad.', 'Radiographic findings': 'Orthopantogram showed extensive alveolar bone loss in all remaining teeth. The alveolar bone around the mobile teeth was devoid of definable lamina dura. An extensive alveolar bone loss was noted, giving the teeth 31, 41 and 43 a “floating in air appearance,” which were extracted afterwards. Radiographically, right and left lateral oblique radiographs show angular bone loss and periodontal widening present in relation with 36 and 46. There are developing tooth germs of permanent tooth are also seen.', 'Immunological defects': 'CTSC is involved in a wide variety of immune and inflammatory responses. It plays an essential role in activating serine proteinases expressed in the granules of bone marrow derived cells from both the myeloid and lymphoid series. The serine proteinases are implicated in a variety of inflammatory and immune processes, including phagocytic destruction of bacteria and activation of phagocytic cells and T-lymphocytes. Therefore, deficiency of CTSC function will result in loss of immunological response, leading to liability of infection. Recently, impairment of natural killer (NK) cell cytotoxic function is the first consistent immune dysfunction reported in PLS. This suggests that the impaired NK cell cytotoxicity might contribute to the pathogenesis of PLS associated periodontitis. A defect that principally interferes in phagocytic function is likely to give rise to aggressive periodontitis of PLS since nearly identical features occur in other defects of phagocytic function. The loss of CTSC function and subsequent inactivity of neutrophil serine proteinases may cause deregulation of localized polymorphonuclears response in inflamed periodontal tissues, leading to the severe tissue destruction in PLS.', 'Case 1': 'A 14-year-old girl, visited to outpatient Department of Periodontia, Government Dental College and Hospital, Ahmedabad, India with chief complain of premature loss of deciduous and permanent teeth and mobility in remaining teeth. She was the first child born to apparently healthy non-consanguineous parents. History revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4-5 years. Similarly, her permanent teeth were lost prematurely after erupting normally. Patient was having complained of mobility and bleeding gum before 2 years, visited a periodontist and undergone treatment in the form of periodontal flap surgery. After one and half year, patient was having same complain and came to Government Dental College and Hospital, Ahmedabad. There was no family history of ichthyosis or hereditary or acquired palmoplanter keratodermas. The patient also gave a history of development of fissures, thickening and flaking in the skin of palms and soles that resulted in peeling off of skin leaving red thin area underneath since age of 3-4 years. She had exacerbation and remissions of the skin lesions since early childhood, visiting dermatologist regularly, but no improvement was seen. She repeatedly contracted systemic infections.'}", "questions": ["What observations were noted about the patient's fingers during the examination?"], "ground_truth_arguments": ["The fingers were pointed giving clawed appearance"]}
{"id": "CaseReportBench:train-237", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Patient': 'The patient was the second child of nonconsanguineous parents who was born after an uneventful pregnancy of 42 weeks. At birth, early findings comprised congenital hypotonia, low facial expression, and inverted feet. He was diagnosed with swallowing problems and gastroesophageal reflux. Dysmorphic features included brachyturricephaly, low-set ears, hypermetropia, facies myopathica, and hyperlaxity with arachnodactyly. Due to positive family history of minicore myopathy (his sister died with this condition at age 5 due to aspiration), an early muscle biopsy was performed. The initial histological findings suggested a possible multi/minicore disease. The patient developed chronic lactic acidemia (lactate 2.3–4 mmol/l, C: <2.1 mmol/l), 3-methylglutaconic aciduria (80 μmol/l, C: <18 μmol/mmol creatinine), and recurrent hypoglycemic episodes. Serum alanine levels (610 μmol/l, C: <450 μmol/l) and creatine kinase (CK) levels (500–800 U/l, C: 180 U/l) were moderately increased. No motor development was observed with regular physiotherapy; for further clarification of the diagnosis, a second muscle biopsy was performed at the age of 6 years. The biopsy results showed the characteristic picture of central core disease: electron microscopy detected abnormal, large mitochondria with crystalline inclusions and biochemical evidence of severe mitochondrial dysfunction (Table 1 ). Genetic studies including mitochondrial DNA sequencing, sequencing of the nuclear-coded structural complexes I and III genes, and POLG mutation analysis were all normal. A compound heterozygous RYR1 mutation in complementary DNA (cDNA) was found. The parents were heterozygous carriers (Wortmann et al. 2009 ). At age 9 years, while receiving regular physiotherapy, the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures. Further physical signs were bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees. He had no extraocular muscle anomalies and no exercise-induced myalgia. Table 1 Abnormal biochemical and genetic features Analyses performed Results Biochemistry ATP production nmol/h/mUCS (N 42–81) 4 Complex I mU/UCS (N 70–251) 58 Complex II mU/UCS (N 335–749) 312 Complex III mU/UCS (N 2200–6610) 725 Complex IV mU/UCS (N 810–3120) 483 Complex deficiencies I, II, III, IV Genetics Paternal mutation p. His581GlnfsX29 (exon 16) Maternal mutation p.Val14849Ile (exon 101) ATP adenosine triphosphate, UC unconditioned stimulus, N normal'}", "questions": ["Which gene is implicated in the patient's diagnosis?"], "ground_truth_arguments": ["RYR1"]}
{"id": "CaseReportBench:train-47", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': \"In 1986, a previously healthy 18-year-old male presented to our hospital with a 1-week history of fever, headache and vomiting. Meningism, but no focal neurological signs, was noted on examination. Lumbar puncture was performed, revealing slight elevation of protein in the cerebrospinal fluid (CSF) but no increased cell count. Over the next few days, right-sided weakness developed. Electroencephalogram demonstrated left parieto-occipital focal slowing. Results of T1/T2-weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area. The patient was commenced on acyclovir, but herpes serology came back negative. When generalized tonic-clonic seizures ensued, anticonvulsant therapy with carbamazepine was established. The patient was finally discharged with a provisional diagnosis of viral encephalitis, although no causative agent was found. No residual neurological deficits persisted. In 1989, hearing impairment was first documented and ascribed to the previous encephalitis. The following years saw recurrent admissions for seizures, and sodium valproate was added. The patient's functional status deteriorated progressively. In 1999, he was diagnosed with diabetes mellitus, requiring insulin straightaway. The patient's sister was admitted to our department in October 2010 with gross oedema of the legs. Her medical history included diabetes and sensorineural deafness. Advanced renal impairment was noted. In view of her phenotype, we suspected maternally inherited diabetes and deafness (MIDD). The 3243A>G mutation in the MT-TL1 gene of the mitochondrial DNA (mtDNA) was subsequently demonstrated in blood leucocytes, confirming the diagnosis. When her brother was admitted in October 2011 for anorexia, we re-evaluated his past medical notes. In the initial CSF analysis, no lactate levels had been checked. Electrocardiogram showed Wolff–Parkinson–White syndrome. Macular dystrophy, but no signs of diabetic retinopathy, was found on fundoscopy. CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto-occipital hypodensity, likely representing a previous stroke-like event (Fig. 1 ). Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) was deemed a likely explanation for his multi-systemic disease and was confirmed by demonstration of the 3243A>G transition in blood and urine. The heteroplasmy rate (the mixture of normal and mutated mitochondrial DNA) was 50 and 90%, respectively. Anticonvulsant therapy was switched to levetiracetam and treatment with coenzyme Q 10 was started. The patient now lives in a nursing home. Follow-up at our unit has been arranged. Figure 1: Cerebral computed tomography of a 40-year-old man showing generalized cerebral atrophy, bilateral basal ganglia calcification (asterisks) and a left parieto-occipital hypodensity (arrow).\"}", "questions": ["What were the protein and cell count findings in the patient's cerebrospinal fluid?", "How did the T1/T2-weighted brain MRI describe the left occipital area?", "What were the results of the herpes serology testing?", "Which lactate measurement was not performed in the initial CSF analysis?", "What abnormalities were reported on the brain CT scan?", "What mitochondrial DNA mutation was identified in blood and urine, and how was heteroplasmy described for each sample?"], "ground_truth_arguments": ["slight elevation of protein in the cerebrospinal fluid ( CSF ) but no increased cell count", "Results of T1 / T2 - weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area.", "herpes serology came back negative", "In the initial CSF analysis, no lactate levels had been checked", "CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto - occipital hypodensity, likely representing a previous stroke - like event", "demonstration of the 3243A > G transition in blood and urine. The heteroplasmy rate ( the mixture of normal and mutated mitochondrial DNA ) was 50 and 90 %, respectively", "Cerebral computed tomography of a 40 - year - old man showing generalized cerebral atrophy, bilateral basal ganglia calcification ( asterisks ) and a left parieto - occipital hypodensity ( arrow"]}
{"id": "CaseReportBench:train-173", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What is the patient's mental development status?"], "ground_truth_arguments": ["normal mental development,"]}
{"id": "CaseReportBench:train-376", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What are the patient's height, weight, body mass index (BMI), and blood pressure measurements as reported in the case?"], "ground_truth_arguments": ["height of 158 cm ( – 1 SD ), weight of 85 kg ( > 2 SD ), body mass index ( BMI ) of 34.13 kg / m 2 ( greater than the 97th centile ) and blood pressure of 150/80 mmHg."]}
{"id": "CaseReportBench:train-112", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case presentation': \"This is a 20-year-old female with a 6-month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days. Her vital signs on admission showed uncontrolled hypertension (BP = 148/118 mm Hg) and tachycardia (HR = 120 bpm). She was unable to eat during the last few days. On the second day of her admission, she had two generalized tonic–clonic seizures. She received lorazepam and levetiracetam, and her clinical seizures resolved; however, she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region. The patient was transferred to the ICU for blood pressure control and was started on treatment with acyclovir, antihypertensive medications, and antibiotics. She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid (CSF) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus . The brain MRI showed PRES ( Fig. 1 ). Because the stat EEG showed LPDs + F, a highly epileptogenic pattern, cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording. Therefore, clinical and electrographic seizures completely subsided with treatment. Acyclovir was discontinued, and high dose steroids were started, considering the possibility of immunological and inflammatory etiologies. The patient showed clinical improvement, but her abdominal pain persisted, and the diagnosis of an acute porphyria was suspected. Urine, then serum and fecal porphyrins were requested. The results were as follows: urine PBG level was 177.4 μmol/L (reference: 0 to 0.88 μmol/L), serum porphyrin level was 58 nmol/L (reference: 0 to 15 nmol/L), fecal coproporphyrin was 18 nmol/g (reference: 0 to 45 nmol/g), and fecal protoporphyrin was 10 nmol/g (reference: 0–100 nmol/g). Taken together, the highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels, were suggestive of AIP. The patient's abdominal pain resolved in less than 24 h with carbohydrate (glucose) loading and highly caloric diet. Therefore, intravenous hemin was not necessary at that time. She was discharged home in stable conditions and offered to follow up at a porphyria center of her choice for further confirmatory genetic testing, management, and counseling. The patient was seen in our epilepsy outpatient clinic one month later. She was not taking any medications. She was asymptomatic, and her neurological exam was normal. A follow-up brain MRI showed remarkable improvement.\"}", "questions": ["What is the confirmed metabolic diagnosis identified in this patient?", "Which specific type of porphyria does the case conclude the patient has?", "Based on the laboratory findings, what acute porphyria was diagnosed?", "What inborn error of metabolism is responsible for the patient's presentation?", "What is the final diagnosis related to the elevated urine PBG and plasma porphyrin levels?"], "ground_truth_arguments": ["AIP"]}
{"id": "CaseReportBench:train-569", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case report': \"A 27-year-old nulliparous woman, a diagnosed case of 21-hydroxylase deficient simple virilizing form of classic CAH visited our department from the endocrinology department for pregnancy maintenance. Her diagnosis had been identified at eleven years old with a high testosterone level, raised 17-hydroxyprogeterone level, enlarged clitoris and normal karyotype (46, XX). At the age of 12, she underwent clitoral resection and vaginoplasty at urology department of our hospital. She took dexamethasone (minimum dose 0.5 mg/day to maximum dose 1.0 mg/day) after operation. Four months later, her breasts expanded and in six months' time, menstruation began. The treatment sustained without any other complication. The treatment had continued and urology department referred this case to endocrinology department when she was 27 years old. Medication was changed to prednisolone and the endocrinology department had prescribed it (minimum dose 10 mg/day to maximum dose 20 mg/day) before pregnancy. She married at 25 years old and had a spontaneous abortion at 26 years old. After the abortion, she got pregnant spontaneously without any trial of assisted reproductive technology. At 12+3 week of gestation, she first visited our department. The first trimester screening conducted at the first visit of 12+3 week of gestation was normal and quad test conducted at 16+3 week of gestation was also normal. She was diagnosed with gestational diabetes mellitus as blood sugar was mildly increased than normal range in the 100 g oral glucose tolerance test conducted at 24+6 week of gestation. Lifestyle modification was recommended to the patient and blood sugar was well-controlled without any medication. Ultrasonography was performed at two to four weeks. The development of fetus was appropriate to the gestational age without any sign of intrauterine growth retardation or large for gestational age. During pregnancy, she continued to take prednisolone (minimum dose 7.5 mg/day to maximum dose 20 mg/day) on demand at endocrinology department. Cesarean section was preferred other than vaginal delivery, as she had cephalopelvic disproportion on examination and history of vaginoplasty. She delivered female weighs 2,990 g by elective cesarean section at 38+4 week of gestation. The baby exhibited normal 7 Apgar score and did not require oxygen or respiratory assistance. The external genitalia was normal and there was a sign of normal karyotype (46, XX) in the result of chromosomal study. After the delivery, the patient had took prednisolone (15 mg/day) consistently for the CAH. After one time of spontaneous abortion, 3 years later, at the age of 30, she became pregnant of the second baby spontaneously. She was diagnosed with gestational diabetes mellitus due to the mildly increased level of blood sugar at the 100 g oral glucose tolerance test conducted at 23+4 week of gestation, however, the blood sugar was well-controlled by life style modification without medication. The development of fetus was appropriate to the gestational age and antenatal care did not show any particular sign. During this pregnancy, she continuously took the prednisolone (minimum dose 7.5 mg/day to maximum dose 15 mg/day) prescribed by endocrinology department. She delivered 3,250 g female baby at 38+2 week of gestation, by cesarean section. The baby exhibited normal Apgar score and did not require oxygen or respiratory assistance. Four years old baby and eleventh month old bay have shown normal external genitalia and normal development up to now.\"}", "questions": ["At what age was the patient first diagnosed with 21‑hydroxylase deficient congenital adrenal hyperplasia?"], "ground_truth_arguments": ["eleven years old"]}
{"id": "CaseReportBench:train-229", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': \"The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. The proband (III-1) ( Fig. 1 ) was a 37-year-old man with severe dizziness and double vision. He had first experienced visual and gait disturbances at 10 years of age. The neurological examination performed on admission revealed mild disturbance of cognitive function (Revised Wechsler Adult Intelligence Scale: total IQ=73, performance IQ=58, verbal IQ=91). Neurological disturbances were observed including bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze-evoked nystagmus, and dysarthria. The light reflex was prompt. No disturbances in cranial nerves I, VII, VIII, and XII were detected. Tremor appeared in his neck, but other involuntary movements including palatal myoclonus were not observed. While his upper and lower limbs showed no paralysis, they exhibited severe cerebellar ataxia and hypotonia. No abnormal findings were detected in his deep tendon reflex and sensory system. Ophthalmological examination revealed atrophy of the optic nerve, but there were no pigmentation changes of the retina. Blood and cerebrospinal fluid analyses were normal. Ergometer exercise did not up-regulate his serum lactate and pyruvate. Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1-weighted imaging, and high signal intensities on T2-weighted imaging, suggesting degeneration ( Fig. 2C and D ). The patient was diagnosed as having LHON plus olivocerebellar degeneration. Although the thyrotropin-releasing drug taltirelin did not relieve his symptoms, adenosine triphosphate disodium reduced his dizziness. The patient's mother (II-2) and uncle (II-3) also had optic neuropathy, but other neurological abnormalities such as ataxia and dystonia were not observed. The patient's mother has a history of subarachnoid hemorrhage. MRI of his mother disclosed mild atrophy of the optic nerve ( Fig. 2E ), pons, and cerebellum ( Fig. 2F-H ). No signal changes were observed in the inferior olivary nucleus ( Fig. 2F-H ). We were unable to confirm the detailed clinical information of the proband's grandmother (I-2).\", 'Mutation analyses of mtDNA': \"Blood samples were obtained from the patient and his mother with their informed consent, and the methods used were approved by the institutional review board of Tottori University Hospital. Both mtDNA and genomic DNA were extracted by standard procedures. The polymerase chain reaction (PCR) was carried out using the primers 5'-CCTCCCTACTATGCCTAGAAGGA-3' and 5'-TTTGGGTTGTGGCTCAGTGT-3' for ND4, including 11778G analysis, and 5'-AGTTCAGACCGGAGTAATCCAG-3' and 5'-AGGGTTGTAGTAGCCCGTAG-3' for ND1 . The primer set for ND4 was designed to identify G11778A mutations, which is the main mutation for LHON. The primer set for ND1 was designed to detect not only the T3394C mutation as a minor mutation for LHON but also an A3243G mutation that is frequently detected in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. PCR products that included the previously reported candidate abnormal points were analyzed by capillary electrophoresis using an automated DNA sequencer. The G11778A and T3394C mutations were identified, while the A3243G mutation was not detected. The mutations in the mtDNA were confirmed by performing PCR-restriction fragment length polymorphism (RFLP), in which the PCR products were digested using either HaeIII (for T3394C) or Tsp45I (for G11778A). In order to quantify the heteroplasmic mutation of G117 78A, we prepared vector constructs including 11778G or 11 778A, and semiquantitative analyses of G11778A were performed using a mixture of each with several rate standards (described in Fig. 4 ). Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr-to-His amino acid substitution in ND1. PCR-RFLP data revealed that the T3394C mutation present in both the proband (III-1) and his mother (II-2) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg-to-His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR-RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92% heteroplasmic G11778A mutation, and II-2 had a 70% heteroplasmic G11778A mutation ( Fig. 4C ). Established genetic abnormalities associated with cerebellar ataxia including polyglutamine diseases were not found.\"}", "questions": ["At what age did the proband first experience visual and gait disturbances?"], "ground_truth_arguments": ["10 years of age"]}
{"id": "CaseReportBench:train-589", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 3-year-old boy was admitted to our emergency department because of convulsions and unconsciousness. He had been diagnosed as 21-hydroxylase deficiency at birth. He had been taking oral steroid (hydrocortisone) replacement therapy since then. His parents had stopped steroid therapy without the knowledge of the physician 3 days before the symptoms started. They were admitted to our hospital 6 hours after the onset of the symptoms. He was in coma and had seizures on admission. Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg/dl and white blood cell (WBC) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies. Intravenous hydrocortisone treatment was initiated. Electroencephalography showed focal epileptic activity. Routine brain MRI was performed. Diffusion weighted images (DWI) and susceptibility weighted images (SWI) were also obtained in order to detect ischemia and hemorrhage. T2-weighted and fluid attenuated inversion recovery (FLAIR) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical-subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical-subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient (ADC) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto-occiptal cortical-subcortical regions due to hypoxia and hypoglisemia. We obtained follow-up brain MRI on fifth, twelfth, and twentieth days once the treatment has started. DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae.'}", "questions": ["What was the patient's age at the time of presentation?"], "ground_truth_arguments": ["3 - year - old"]}
{"id": "CaseReportBench:train-196", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}", "questions": ["What demographic information is provided for the patient?", "What details are given about the patient’s place of origin?", "What is reported regarding the parental relationship in terms of consanguinity?", "What gastrointestinal symptoms are mentioned, and what is known about their onset or duration?"], "ground_truth_arguments": ["An 8 - year - old girl of non - consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department"]}
{"id": "CaseReportBench:train-402", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Presentation': \"We present a case of cardiac paraganglioma with left coronary artery involvement. The patient was a 22-year-old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension. Results of transthoracic echocardiography and renal Doppler imaging were normal, and plasma and urine metanephrine levels were within normal limits. Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation. New transthoracic echocardiography showed high velocities in the pulmonary artery and a mass with intermediate echogenicity located at the base of the heart in close relation to the aorta and the pulmonary artery, extending into the left atrioventricular groove ( Figure 1, Videos 1 and 2 ). Free metanephrines in plasma (noradrenaline 4,886.67 pg/mL) and urine (noradrenaline 1,426.9 μg/24 h) were high. Figure 1 Transthoracic echocardiography. Shown is a mass ( white arrow ) with intermediate echogenicity in relation to the great vessels. To obtain better characterization, cardiac magnetic resonance was performed and showed a middle mediastinal mass located in the left atrioventricular groove, extending posteriorly to the left atrial roof and almost surrounding the pulmonary artery anteriorly. The mass was closely associated with the aortic root, but the emergence and path of the left coronary artery and its branches were not adequately visualized ( Figure 2 ). Tissue characterization sequences showed a mass with a heterogeneous appearance on T2-weighted sequences and slightly hyperintense on T1-weighted and T2 with fat saturation sequences ( Figure 2 ). Important mass vascularization was demonstrated with the perfusion sequence, which showed rapid uptake of contrast shortly after its administration. We also found focal late gadolinium enhancement at the periphery of the mass, with no enhancement at its center, a finding that was considered highly suggestive of a paraganglioma ( Figure 3 ). Fluorine-18 fluorodeoxyglucose positron emission tomography was also performed, demonstrating a highly metabolic mass ( Figure 4 ). Figure 2 Cardiac magnetic resonance. (1) Coronal: isointense mass in relation to the left atrial roof. (2) Two-chamber longitudinal: isointense mass in the left atrioventricular groove. (3,4) Axial: mass in relation to the aortic root and the pulmonary artery. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 3 Cardiac magnetic resonance. Delayed enhancement. Focal deposit of gadolinium in the periphery of the mass. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 4 Positron emission tomography with 18F-fluorodeoxyglucose (10 mCi). Hypermetabolic mass in the middle mediastinum. Images reproduced with permission from Clínica del Country-Bogotá-Colombia. The case was discussed with the heart team and other departments, such as endocrinology and oncology, concluding that the patient had a clear indication for surgery, with α- and β-blockade, high sodium intake, and adequate hydration before the procedure. However, given that there were doubts regarding the emergence of the left coronary artery and its pathway, coronary angiotomography was performed. The mass was found to surround the left main coronary artery, the proximal segment of the left anterior descending coronary artery, the circumflex coronary artery, and two septal arteries, as well as the great cardiac vein ( Figure 5, Figure 6, Figure 7 ). At that time, and because of these findings, the intervention was considered to be a high-risk procedure. Isotopic radiation with 131 I meta-iodine benzyl guanidine (MIBG) was considered as a palliative intervention, but this approach was rejected because of the risk for hypertensive crises of unpredictable severity. Another approach that was considered was the use of octeotride, but this alternative was not accepted by the multidisciplinary group, because there was a risk for irradiation of adjacent tissue, including the coronary arteries, with an unknown benefit. The risk/benefit assessment of this therapy did not favor the patient either, and surgery was thought to be the only option. Coronary angiography was done looking for a main feeding artery that could be embolized preoperatively to reduce the tumor size and intraoperative blood loss. However, embolization could not be done, because there were many small feeding arteries coming from the left main coronary artery ( Figure 8 ). The patient underwent mass resection, requiring a complete transverse arteriotomy of the ascending aorta, pulmonary trunk, and section of the superior vena cava. The mass was exposed using caudal traction and was found to be closely associated with the posterior wall of the ascending aorta, the pulmonary artery, and the left atrial roof, without infiltration of these structures. Involvement of the left coronary artery trunk was documented, which required ligation and revascularization of the anterior descending coronary artery and the circumflex coronary artery. The mass could be completely resected ( Figure 9 ). Figure 5 Coronary computed tomography. Mass surrounding the left main coronary artery and the proximal segment of the anterior descending and the circumflex coronary arteries. Figure 6 Coronary computed tomography. Mass surrounding the pulmonary artery. Figure 7 Coronary computed tomography. Mass located in the left atrioventricular groove. Figure 8 Coronary arteriography. Mass irrigated by multiple small vessels arising from the anterior descending coronary artery. Figure 9 Surgical specimen. Resected mass. The patient progressed well and was able to be extubated and have her vasopressor support discontinued. Follow-up echocardiography showed that systolic function was moderately affected, with an ejection fraction of 35% and diffuse hypokinesia, which was more pronounced in the anterior descending coronary artery territory. Because of these findings, new coronary angiography was performed, ruling out saphenous bridge compromise ( Figure 10 ). Further follow-up echocardiography showed improvement in systolic function, with an ejection fraction of 55% and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure ( Figure 11, Videos 3 and 4 ). Figure 10 Coronary angiography. Saphenous bridge patent to the anterior descending artery, without lesions. Figure 11 Transthoracic echocardiography. (1) Parasternal view in diastole: pericardial effusion. (2) Parasternal view in systole: akinesia of the basal anteroseptal segment. The pathology report of the surgical specimen described round and oval cells in an organoid pattern with fine chromatin nuclei and degenerative focal atypia ( Figure 12 ). These findings and the immunohistochemical studies were compatible with a paraganglioma. The genetic study showed a succinate dehydrogenase subunit B mutation. The patient progressed satisfactorily and was discharged. One month later, it was found that one of her father's cousins had a para-aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain. Figure 12 Round and oval cells, arranged in an organoid pattern, with degenerative focal atypia.\"}", "questions": ["What symptom did the patient report that involves pain in the head?"], "ground_truth_arguments": ["headache."]}
{"id": "CaseReportBench:train-54", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Presentation': \"We present a case of cardiac paraganglioma with left coronary artery involvement. The patient was a 22-year-old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension. Results of transthoracic echocardiography and renal Doppler imaging were normal, and plasma and urine metanephrine levels were within normal limits. Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation. New transthoracic echocardiography showed high velocities in the pulmonary artery and a mass with intermediate echogenicity located at the base of the heart in close relation to the aorta and the pulmonary artery, extending into the left atrioventricular groove ( Figure 1, Videos 1 and 2 ). Free metanephrines in plasma (noradrenaline 4,886.67 pg/mL) and urine (noradrenaline 1,426.9 μg/24 h) were high. Figure 1 Transthoracic echocardiography. Shown is a mass ( white arrow ) with intermediate echogenicity in relation to the great vessels. To obtain better characterization, cardiac magnetic resonance was performed and showed a middle mediastinal mass located in the left atrioventricular groove, extending posteriorly to the left atrial roof and almost surrounding the pulmonary artery anteriorly. The mass was closely associated with the aortic root, but the emergence and path of the left coronary artery and its branches were not adequately visualized ( Figure 2 ). Tissue characterization sequences showed a mass with a heterogeneous appearance on T2-weighted sequences and slightly hyperintense on T1-weighted and T2 with fat saturation sequences ( Figure 2 ). Important mass vascularization was demonstrated with the perfusion sequence, which showed rapid uptake of contrast shortly after its administration. We also found focal late gadolinium enhancement at the periphery of the mass, with no enhancement at its center, a finding that was considered highly suggestive of a paraganglioma ( Figure 3 ). Fluorine-18 fluorodeoxyglucose positron emission tomography was also performed, demonstrating a highly metabolic mass ( Figure 4 ). Figure 2 Cardiac magnetic resonance. (1) Coronal: isointense mass in relation to the left atrial roof. (2) Two-chamber longitudinal: isointense mass in the left atrioventricular groove. (3,4) Axial: mass in relation to the aortic root and the pulmonary artery. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 3 Cardiac magnetic resonance. Delayed enhancement. Focal deposit of gadolinium in the periphery of the mass. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 4 Positron emission tomography with 18F-fluorodeoxyglucose (10 mCi). Hypermetabolic mass in the middle mediastinum. Images reproduced with permission from Clínica del Country-Bogotá-Colombia. The case was discussed with the heart team and other departments, such as endocrinology and oncology, concluding that the patient had a clear indication for surgery, with α- and β-blockade, high sodium intake, and adequate hydration before the procedure. However, given that there were doubts regarding the emergence of the left coronary artery and its pathway, coronary angiotomography was performed. The mass was found to surround the left main coronary artery, the proximal segment of the left anterior descending coronary artery, the circumflex coronary artery, and two septal arteries, as well as the great cardiac vein ( Figure 5, Figure 6, Figure 7 ). At that time, and because of these findings, the intervention was considered to be a high-risk procedure. Isotopic radiation with 131 I meta-iodine benzyl guanidine (MIBG) was considered as a palliative intervention, but this approach was rejected because of the risk for hypertensive crises of unpredictable severity. Another approach that was considered was the use of octeotride, but this alternative was not accepted by the multidisciplinary group, because there was a risk for irradiation of adjacent tissue, including the coronary arteries, with an unknown benefit. The risk/benefit assessment of this therapy did not favor the patient either, and surgery was thought to be the only option. Coronary angiography was done looking for a main feeding artery that could be embolized preoperatively to reduce the tumor size and intraoperative blood loss. However, embolization could not be done, because there were many small feeding arteries coming from the left main coronary artery ( Figure 8 ). The patient underwent mass resection, requiring a complete transverse arteriotomy of the ascending aorta, pulmonary trunk, and section of the superior vena cava. The mass was exposed using caudal traction and was found to be closely associated with the posterior wall of the ascending aorta, the pulmonary artery, and the left atrial roof, without infiltration of these structures. Involvement of the left coronary artery trunk was documented, which required ligation and revascularization of the anterior descending coronary artery and the circumflex coronary artery. The mass could be completely resected ( Figure 9 ). Figure 5 Coronary computed tomography. Mass surrounding the left main coronary artery and the proximal segment of the anterior descending and the circumflex coronary arteries. Figure 6 Coronary computed tomography. Mass surrounding the pulmonary artery. Figure 7 Coronary computed tomography. Mass located in the left atrioventricular groove. Figure 8 Coronary arteriography. Mass irrigated by multiple small vessels arising from the anterior descending coronary artery. Figure 9 Surgical specimen. Resected mass. The patient progressed well and was able to be extubated and have her vasopressor support discontinued. Follow-up echocardiography showed that systolic function was moderately affected, with an ejection fraction of 35% and diffuse hypokinesia, which was more pronounced in the anterior descending coronary artery territory. Because of these findings, new coronary angiography was performed, ruling out saphenous bridge compromise ( Figure 10 ). Further follow-up echocardiography showed improvement in systolic function, with an ejection fraction of 55% and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure ( Figure 11, Videos 3 and 4 ). Figure 10 Coronary angiography. Saphenous bridge patent to the anterior descending artery, without lesions. Figure 11 Transthoracic echocardiography. (1) Parasternal view in diastole: pericardial effusion. (2) Parasternal view in systole: akinesia of the basal anteroseptal segment. The pathology report of the surgical specimen described round and oval cells in an organoid pattern with fine chromatin nuclei and degenerative focal atypia ( Figure 12 ). These findings and the immunohistochemical studies were compatible with a paraganglioma. The genetic study showed a succinate dehydrogenase subunit B mutation. The patient progressed satisfactorily and was discharged. One month later, it was found that one of her father's cousins had a para-aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain. Figure 12 Round and oval cells, arranged in an organoid pattern, with degenerative focal atypia.\"}", "questions": ["What type of cardiac tumor was identified, and was any coronary artery reported as being involved?", "What symptoms and blood‑pressure abnormalities prompted investigation for secondary hypertension in this young patient?", "What were the findings of ambulatory blood‑pressure monitoring, which general class of antihypertensive therapy was initiated, and what new cardiac murmur was subsequently detected after persistent symptoms?", "What findings were reported on follow‑up echocardiography regarding left‑ventricular systolic function, regional wall‑motion abnormalities, and the presence of pericardial effusion?"], "ground_truth_arguments": ["cardiac paraganglioma with left coronary artery involvement.", "recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension", "Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation", "follow - up echocardiography showed improvement in systolic function, with an ejection fraction of 55 % and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure"]}
{"id": "CaseReportBench:train-433", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': \"The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. The proband (III-1) ( Fig. 1 ) was a 37-year-old man with severe dizziness and double vision. He had first experienced visual and gait disturbances at 10 years of age. The neurological examination performed on admission revealed mild disturbance of cognitive function (Revised Wechsler Adult Intelligence Scale: total IQ=73, performance IQ=58, verbal IQ=91). Neurological disturbances were observed including bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze-evoked nystagmus, and dysarthria. The light reflex was prompt. No disturbances in cranial nerves I, VII, VIII, and XII were detected. Tremor appeared in his neck, but other involuntary movements including palatal myoclonus were not observed. While his upper and lower limbs showed no paralysis, they exhibited severe cerebellar ataxia and hypotonia. No abnormal findings were detected in his deep tendon reflex and sensory system. Ophthalmological examination revealed atrophy of the optic nerve, but there were no pigmentation changes of the retina. Blood and cerebrospinal fluid analyses were normal. Ergometer exercise did not up-regulate his serum lactate and pyruvate. Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1-weighted imaging, and high signal intensities on T2-weighted imaging, suggesting degeneration ( Fig. 2C and D ). The patient was diagnosed as having LHON plus olivocerebellar degeneration. Although the thyrotropin-releasing drug taltirelin did not relieve his symptoms, adenosine triphosphate disodium reduced his dizziness. The patient's mother (II-2) and uncle (II-3) also had optic neuropathy, but other neurological abnormalities such as ataxia and dystonia were not observed. The patient's mother has a history of subarachnoid hemorrhage. MRI of his mother disclosed mild atrophy of the optic nerve ( Fig. 2E ), pons, and cerebellum ( Fig. 2F-H ). No signal changes were observed in the inferior olivary nucleus ( Fig. 2F-H ). We were unable to confirm the detailed clinical information of the proband's grandmother (I-2).\", 'Mutation analyses of mtDNA': \"Blood samples were obtained from the patient and his mother with their informed consent, and the methods used were approved by the institutional review board of Tottori University Hospital. Both mtDNA and genomic DNA were extracted by standard procedures. The polymerase chain reaction (PCR) was carried out using the primers 5'-CCTCCCTACTATGCCTAGAAGGA-3' and 5'-TTTGGGTTGTGGCTCAGTGT-3' for ND4, including 11778G analysis, and 5'-AGTTCAGACCGGAGTAATCCAG-3' and 5'-AGGGTTGTAGTAGCCCGTAG-3' for ND1 . The primer set for ND4 was designed to identify G11778A mutations, which is the main mutation for LHON. The primer set for ND1 was designed to detect not only the T3394C mutation as a minor mutation for LHON but also an A3243G mutation that is frequently detected in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. PCR products that included the previously reported candidate abnormal points were analyzed by capillary electrophoresis using an automated DNA sequencer. The G11778A and T3394C mutations were identified, while the A3243G mutation was not detected. The mutations in the mtDNA were confirmed by performing PCR-restriction fragment length polymorphism (RFLP), in which the PCR products were digested using either HaeIII (for T3394C) or Tsp45I (for G11778A). In order to quantify the heteroplasmic mutation of G117 78A, we prepared vector constructs including 11778G or 11 778A, and semiquantitative analyses of G11778A were performed using a mixture of each with several rate standards (described in Fig. 4 ). Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr-to-His amino acid substitution in ND1. PCR-RFLP data revealed that the T3394C mutation present in both the proband (III-1) and his mother (II-2) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg-to-His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR-RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92% heteroplasmic G11778A mutation, and II-2 had a 70% heteroplasmic G11778A mutation ( Fig. 4C ). Established genetic abnormalities associated with cerebellar ataxia including polyglutamine diseases were not found.\"}", "questions": ["What diagnostic term is used to describe the proband's condition in the case report?", "How does the report characterize the coexistence of optic neuropathy and cerebellar abnormalities?"], "ground_truth_arguments": ["LHON plus olivocerebellar degeneration"]}
{"id": "CaseReportBench:train-545", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["What prior gynecologic condition was documented in the patient's medical history?", "What findings did the bedside transvaginal ultrasound report concerning the ovaries?", "In which phase of her menstrual cycle was the patient when she presented with symptoms?", "What electrolyte abnormality and serum creatinine level were noted on the initial laboratory studies?", "What change in urine color did the patient describe?"], "ground_truth_arguments": ["ruptured ovarian cyst,", "A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen", "was in the luteal phase of her menstrual cycle", "hypokalemia ( potassium 3.4 mmol / L, reference range 3.5–5.1 mmol / L ), and an elevated creatinine 1.14 mg / dl ( baseline around 0.80 mg / dl ).", "red discoloration of urine"]}
{"id": "CaseReportBench:train-403", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': 'The patient presented at age seven years with intermittent vomiting, diarrhea, constipation, weight loss and fatigue that has persisted for over 18 months. Routine work-up showed significant metabolic acidosis with low serum bicarbonate concentrations. He was started on oral sodium citrate and admitted for evaluation, which revealed low serum glucose of 3.05 mmol/L (55 mg/dL) and very low plasma l -carnitine (total carnitine:7 μmol/L, reference range: 25–69). Serum creatine phosphokinase (CK) and transaminases were elevated and continued to increase as he clinically deteriorated, with CK peaking at 202 μkat/L (12,086 U/L), AST at 341 U/L and ALT at 190 U/L. Ophthalmologic and audiologic exams were normal. Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation disorders. The patient had started on carnitine and cornstarch but continued to deteriorate, with multiple admissions for ketotic hypoglycemia and severe lactic acidosis. Brain magnetic resonance imaging was normal, while brain magnetic resonance spectroscopy (MRS) showed lactate peaks in the left basal ganglion and lateral ventricle. As this finding was suggestive of a mitochondrial disorder, treatment with coenzyme Q10, riboflavin, creatine monohydrate, alpha-lipoic acid, and medium chain triglyceride (MCT) oil was initiated, while continuing carnitine supplementation. Leucovorin was later added due to a low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate level. At age eight, he required a gastric feeding tube (G-tube) placement for malnutrition and continued weight loss. The urine organic acid profile was notable for elevations of lactate, ethylmalonate, 3-methylglutaconate, and branched-chain ketoacids, suggestive of mitochondrial dysfunction. Cultured skin fibroblast testing was performed for suspected defects in fatty acid oxidation, pyruvate carboxylase (EC 6.4.1.1), and pyruvate dehydrogenase complex (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4) with normal results . Analysis of acylcarnitines in cultured skin fibroblasts incubated with palmitic acid and l -carnitine (in vitro probe assay) showed marked elevations of long-chain species, suggestive of carnitine palmitoyltransferase II or carnitine–acylcarnitine translocase deficiency. CSF analysis showed mild elevation of lactate of 3.1 mmol/L (< 2.8), and a low normal level of 5-methyltetrahydrofolate. Transaminitis was initially attributed to a possible GSD; glycogen content was elevated in both liver (10%; control range 3.3 +/− 1.7%) and muscle (3.0%; control range 0.94 +/− 0.55). However, sequencing of PHKA1 and PHKG2 genes (GSD IX) and AGL gene (GSD III) was normal. Activities of debranching enzyme (EC 2.4.1.25 GSD III) and hepatic phosphorylase kinase (GSD IX, EC 2.7.11.19) in the liver and muscle, and glucose-6-phosphatase (GSD Ia, EC 3.1.3.9) in the liver were also normal. Further evaluation for a suspected mitochondrial disorder revealed normal electron transporter chain (ETC) activity in cultured skin fibroblasts. Muscle histopathology demonstrated prominent granular red staining of the fibers with a trichrome stain and numerous mitochondria aggregates by electron microscopy, characteristic of a mitochondrial myopathy ( Fig. 1 ). ETC testing on frozen muscle revealed deficient complex III activity of 455 (mean 1461, standard deviation 473); mtDNA sequencing of the muscle sample revealed a 9 basepair deletion with loss of 3 amino acids Leu-Ala-Thr (m.15319_15327delCCTAGCAAC; p.Leu192_Thr194del, Fig. 2 ) in the MT-CYB gene encoding cytochrome b subunit of complex III, with > 90% mutant load, confirming complex III deficiency. MtDNA sequencing in the liver and blood did not reveal the mutation, although low heteroplasmy for the mutation was detected in uncultured skin fibroblasts. Since the diagnosis, ongoing cardiac evaluations to monitor for cardiomyopathy or rhythm disturbance have been normal. The child dramatically improved with the start of G-tube feeding and dietary supplements, with increased energy level, improved exercise tolerance and progress in academic performance. Previously confined to a wheel chair, he started to walk independently and actively. Lactic acid, transaminases and CK levels have stabilized, although lactate showed occasional elevations as high as 11 mmol/L without symptoms of metabolic decompensation. His G-tube was removed at age 12 years and he stopped taking supplements, and he continues to do remarkably well physically.'}", "questions": ["At what age did the patient first present with symptoms?"], "ground_truth_arguments": ["The patient presented at age seven years"]}
{"id": "CaseReportBench:train-178", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["Can you describe the patient's menarche timing and overall menstrual pattern?"], "ground_truth_arguments": ["menarche at 12 years of age with regular menstrual cycles"]}
{"id": "CaseReportBench:train-307", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case report': 'Phenotypic female twins (A, B) were born at 36+2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g (<10 percentile) in A and 2,040 g (10 to 25 percentile) in B, height was 43 cm (10 to 25 percentile) in A and 44 cm (10 to 25 percentile) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit (NICU). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17-OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17-OHP, elevated ACTH (A, 4,379.2 pg/mL at 23 days of life; B, 11,616.1 pg/mL at 29 days of life), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng/mL/hr). However, the level of plasma cortisol before treatment were normal (8.71 µg/dL initially, 7.11 µg/dL in 2nd sample) in patient A, but low (1.5 µg/dL) in patient B. The results of endocrinologic investigation are shown in Table 1 . The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography (CT) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level (132 to 139 mmol/L) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia (129 to 133 mmo/L) and further evaluation for skin hyperpigmentation. She was treated with oral supplementation of sodium (0.8 to 0.9 mmol/kg) at 11 to 35 days of age, and she discharged from the hospital with normal sodium level after tapering off sodium supplementation at 37 days of age. Patient A was admitted at 38 days of age with adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration. Clinical findings of patient A were suggestive of CLAH and prompted us to order a gene analysis in both twins. Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C>T (p.R182C) in exon 5 and c.722C>T (p.Q258X) in exon 7 ( Fig. 1 ). Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms, except hyponatremia, but she was also diagnosed with CLAH with the same StAR gene mutation with patient A. The results of gene analysis of parents showed heterozygous for the mutations in the StAR gene; the heterozygous gene mutations; c.772C>T in the mother, and c.544C>T in the father, were documented. They showed suboptimal levels of hormone despite of administration of 20 mg/m 2 /24-hr of hydrocortisone, dose of hydrocortisone was increased up to 30 mg/m 2 /24-hr. Both patients have been under steroid supplementation (fludrocortisones 0.2 mg daily in 2 divided doses, and hydrocortisone 12 mg daily in 3 divided doses) at 14 months of age. They showed normal development except retarded physical growth, and hormones and electrolyte levels on follow up are shown as Table 1 . Body weight was 8.8 kg (3 to 10 percentile) in patient A, 9.4 kg (10 to 25 percentile) in patient B, body length was 73.7 cm (3 to 10 percentile) in patient A, 75.4 cm (10 to 25 percentile) in patient B at 14 months of age. They had been regularly followed.'}", "questions": ["What observations of increased skin pigmentation are described in the case report?", "What mentions of skin discoloration or pigmentation abnormalities are reported?"], "ground_truth_arguments": ["hyperpigmentation", "skin hyperpigmentation"]}
{"id": "CaseReportBench:train-577", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made. Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years. There was no other significant positive clinical findings. Case three was a 14-year-old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia. Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth. On examination, he had molluscum contagiosum lesions on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case. Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis. Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern. The features of all these five cases have been summarized in Table 1 .'}", "questions": ["What diagnoses were established for each of the cases described in the report?", "Which diagnosis was assigned to the fifth patient, and how does it differ from the diagnosis given to the first four patients?"], "ground_truth_arguments": ["a diagnosis of dyschromatosis universalis hereditaria ( DUH ) was made", "diagnosis of DUH was made in all the four cases .", "a diagnosis of dyschromatosis symmetrica hereditaria was made"]}
{"id": "CaseReportBench:train-547", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'CASE DESCRIPTION': \"A 41-yr-old man was referred to our emergency room from a local clinic on July 3, 2006, with the impression of acute viral hepatitis due to a remarkable elevation of liver enzymes. He had experienced generalized weakness, dark urine, and jaundice for a two week period. His previous history included community-acquired pneumonia and carpal tunnel syndrome, but neither diabetes mellitus nor hypertension. He complained of impotence, and his mother described precocious puberty and hirsutism beginning at the age of 7. He was not married and had no children. His vital signs were a blood pressure of 115/92 mmHg, a regular pulse of 105/min, and a respiratory rate of 18/min. His height was 152.5 cm (< 3th percentile) and body weight was 72.5 kg. The body mass index was 32.5. Acanthosis nigricans was present in both axillae, and there was central obesity with erythematous, scaly, guttate papules on the lower abdominal skin. He also had a rather ambiguous buffalo hump; however, moon face or red stria was not present ( Fig. 1 ). Total and direct bilirubin levels were elevated at 11.6 mg/dL and 8.6 mg/dL, respectively. The AST and ALT levels were 224 and 1,044 U/L, respectively. Serum BUN level was 9.7 mg/dL, and serum creatinine level was 0.82 mg/dL. Serum electrolytes were normal. Based on a positive anti-HAV IgM titer, he was diagnosed with acute hepatitis A. During the evaluation to exclude other causes of liver dysfunction, a 4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT ( Fig. 2A, B ). We evaluated the endocrine function ( Table 1 ). Twenty-four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements (226.4 µg/24 hr; 122.1 µg/24 hr). Plasma cortisol was within the normal range (7.4 µg/dL), however, ACTH level was very high (676.5 pg/mL). Urine 17-OHCS and 17-ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated (0.414 ng/mL). DHEA-S was within the normal range (1.88 µg/mL). Based on the high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass, we suspected a pituitary corticotrophic adenoma with marked asymmetric adrenal hyperplasia. To confirm the diagnosis of Cushing's syndrome, low- and high-dose dexamethasone suppression tests were performed. Then, 24-hr urine cortisol was markedly suppressed, not only by high-dose dexamethasone but also by low-dose dexamethasone ( Table 2 ); this result essentially eliminates the diagnosis of Cushing's syndrome ( 7, 8 ). We thus suspected CAH based on the short stature, precocious pubarche and marked suppression of 24-hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH. The testosterone level was normal (3.51 ng/mL), but 17α-hydroxyprogesterone (17-OHP) was markedly elevated to 30,000 ng/dL, strongly supporting the diagnosis of a simple virilizing form of CAH. Gene analysis revealed CAH due to 21-hydroxylase deficiency by a compound heterozygote for CYP21 mutations: Ile173Asn (I173N) and Arg357Trp (R357W) ( Fig. 3 ), confirming the diagnosis of a simple virilizing from of CAH due to mutations in CYP21 . We began administration of adrenal steroids. After 6 months of treatment with dexamethasone (0.25 mg daily), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig. 2C, D ). 17-OHP and ACTH levels were normalized to 118 ng/dL and 20.8 pg/mL, respectively, and impotence was improved.\", 'Mutation analysis': \"Genomic DNA was extracted from the peripheral blood leukocytes of patient by using the Wizard Genomic DNA Purification Kit according to the manufacturer's instructions (Promega, Madison, WI, USA). All exons of the CYP21 gene were amplified by PCR on a thermal cycler (Applied Biosystems, Foster City, CA, USA). Direct sequencing was performed using the BigDye Terminator Cycle Sequencing Ready Reaction kit and an ABI Prism 3130 Genetic Analyzer (Applied Biosystems). The sequences were analyzed using the Sequencer program (Gene Codes Corp., Ann Arbor, MI, USA) and were compared to the reference sequences. The numbering of nucleotide positions was done according to the CYP21 DNA sequence, and the Gen-Bank accession number was NM000500.\", 'Biochemical assays': 'Blood samples were obtained in the morning after an overnight fast and a 30-min resting period in the supine position. Hormones were assayed using IRMA kits. For low- or high-dose dexamethasone suppression test, 0.5 or 2 mg dexamethasone was administered 4 times a day for 2 consecutive days.'}", "questions": ["What metabolic or cardiovascular comorbidities (e.g., diabetes mellitus, hypertension) are reported for the patient?", "What signs of early sexual development, such as precocious puberty, pubarche, or hirsutism, are described in the patient’s history?", "What cutaneous and body habitus findings were observed on physical examination?", "What adrenal imaging findings were identified, including any masses and evidence of hyperplasia?", "What were the overall results of the 24‑hour urine catecholamine and VMA tests, and how did the hormone panels (including cortisol, ACTH, 17‑OHCS, 17‑ketosteroids, aldosterone, and DHEA‑S) compare to normal ranges?", "How did the patient’s 24‑hour urine cortisol respond to low‑dose and high‑dose dexamethasone suppression tests?", "What were the serum testosterone and 17‑α‑hydroxyprogesterone levels relative to normal reference ranges?", "What changes in adrenal gland size and hormone levels (including 17‑OHP and ACTH) were observed after six months of dexamethasone therapy?"], "ground_truth_arguments": ["neither diabetes mellitus", "precocious puberty", "Acanthosis nigricans was present in both axillae,", "central obesity", "rather ambiguous buffalo hump; however, moon face or red stria was not present", "4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT", "Twenty - four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements ( 226.4 µg/24 hr; 122.1 µg/24 hr ). Plasma cortisol was within the normal range ( 7.4 µg / dL ), however, ACTH level was very high ( 676.5 pg / mL ). Urine 17 - OHCS and 17 - ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated ( 0.414 ng / mL ). DHEA - S was within the normal range ( 1.88 µg / mL ).", "high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass", "24 - hr urine cortisol was markedly suppressed, not only by high - dose dexamethasone but also by low - dose dexamethasone", "short stature, precocious pubarche and marked suppression of 24 - hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH", "The testosterone level was normal ( 3.51 ng / mL ), but 17α - hydroxyprogesterone ( 17 - OHP ) was markedly elevated to 30,000 ng / dL,", "After 6 months of treatment with dexamethasone ( 0.25 mg daily ), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size", "17 - OHP and ACTH levels were normalized to 118 ng / dL and 20.8 pg / mL"]}
{"id": "CaseReportBench:train-86", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'CASE REPORT': \"A two-month-old female infant was transferred to Seoul National University Children's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg (<3rd percentile). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion. The initial laboratory findings after birth showed the following increased values on the liver function test: aspartate aminotransferase (AST), 176 U/L; alanine aminotransferase (ALT), 106 U/L; total bilirubin, 1.76 mg/dL; and direct bilirubin, 1.2 mg/dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non-diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract. The patient was fed with preterm formula milk without feeding intolerance. No definitive sepsis event occurred during her hospitalization. When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg/dL and a direct bilirubin level of 9.61 mg/dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum-ascites-albumin gradient level was elevated, and portal hypertension was suspected. By the age of 70 days, the infant was transferred to our hospital for further evaluation of persistent ascites suggesting portal hypertension and hyperbilirubinemia. On the day of admission to our unit, the infant's height was 42 cm (<3rd percentile), her weight was 2.9 kg (<3rd percentile), and her head circumference was 33.5 cm (<3rd percentile). A physical examination indicated whole-body jaundice, a markedly distended abdomen with ascites and an umbilical hernia. The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g/dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg/dL, a direct bilirubin level of 6.4 mg/dL, an AST level of 225 U/L and an ALT level of 114 U/L. The albumin level was 2.4 g/dL, and the ammonia level was increased to 149 µg/dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng/mL (normal values are 14.0-647.2 ng/mL), and the transferrin saturation was 97.2%. The serum alpha-fetoprotein level was in the high normal range (19,737.27 ng/mL; normal values are 40-19,953 ng/mL). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging (MRI) verified a diffuse heterogeneous low signal intensity in the liver on T2-weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra-hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non-diagnostic findings. The infant received supportive medical treatment, including fat-soluble vitamins, ursodeoxycholic acid, fresh frozen plasma, lactulose, diuretics, and sodium benzoate. Her general condition and coagulopathy were aggravated, and her vital signs were unstable. She was transferred to the intensive care unit on day 18 of hospitalization for further management. Her mother began the donor evaluation process. Active gastrointestinal bleeding was observed on day 21 of the infant's hospitalization, and an emergency living donor liver transplantation was performed. The infant was 3 months old, and her weight was 3 kg on the day of transplantation. The graft was tailored by reducing its left lateral section. The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining. The infant fully recovered from hepatic failure after liver transplantation. The infant was discharged one month after the operation. She exhibited normal renal function after transplantation. She received medical treatment for hyperkalemia, which occurred after the administration of tacrolimus. Following her discharge, the patient's neurological development was delayed, and she entered rehabilitation with outpatient clinic follow-up in the hospital's neurology department. Assessments by brain MRI and chromosomal study produced normal findings.\"}", "questions": ["What were the infant's anthropometric measurements at admission, and how did they compare to expected growth percentiles?", "What were the infant's initial hematology laboratory results, including white blood cell count, hemoglobin, and platelet levels?", "What coagulation abnormalities were reported, such as prolonged prothrombin time, elevated INR, or evidence of coagulopathy?", "What iron studies were documented, such as serum ferritin level and transferrin saturation, and how were they interpreted relative to normal reference ranges?", "How were the infant's vital signs described during the hospital course?", "What acute gastrointestinal complications were observed during the hospital stay?"], "ground_truth_arguments": ["Coagulopathy was also detected", "height was 42 cm ( < 3rd percentile ), her weight was 2.9 kg ( < 3rd percentile ), and her head circumference was 33.5 cm ( < 3rd percentile", "white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g / dL and a thrombocyte count of 93,000/µL.", "The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng / mL ( normal values are 14.0 - 647.2 ng / mL ), and the transferrin saturation was 97.2 %", "coagulopathy", "her vital signs were unstable", "Active gastrointestinal bleeding"]}
{"id": "CaseReportBench:train-369", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case 2': 'Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady. At the dermatological examination grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region ( Figure 4 ). The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers, confirming the diagnosis of pseudoxanthoma elasticum ( Figure 5 ). Right ophthalmoscopy, retinography and angiography revealed angioid streaks ( Figure 6 ). Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal.', 'Case 1': 'Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family. At the dermatological examination, coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae ( Figure 1 ) were observed. The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis, compatible with the diagnosis of pseudoxanthoma elasticum ( Figure 2 ). Cardiological evaluation did not show changes (normal electrocardiogram and echocardiogram). Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography ( Figure 3 ).'}", "questions": ["What histopathological changes were observed in the dermis?", "What were the findings reported for the electrocardiogram in the cardiovascular assessment?", "What were the findings reported for the echocardiogram in the cardiovascular assessment?"], "ground_truth_arguments": ["The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers", "echocardiogram were normal.", "The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis", "normal electrocardiogram and echocardiogram )"]}
{"id": "CaseReportBench:train-69", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["What were the patient's weight and height as documented in the clinical examination?", "What was the patient's resting pulse rate recorded during the assessment?"], "ground_truth_arguments": ["he weighed 38 kg and his height was 148 cm", "pulse rate was 47 / minute"]}
{"id": "CaseReportBench:train-380", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory. Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE. Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium. The patient is being followed up and has been specifically instructed to report if she becomes pregnant.'}", "questions": ["What is the duration, onset pattern, and initial texture change of the pigmented skin lesions on the neck and abdomen?", "Describe the distribution, color, morphology, and associated skin texture (e.g., softness, laxity, wrinkling, keratotic features) of the papules on the neck and periumbilical area.", "What histological features were observed in the biopsy, specifically regarding the basophilic material in the mid‑dermis and any epidermal discontinuities with extrusion of elastic fibers?"], "ground_truth_arguments": ["pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture,", "multiple brownish - black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal", "fragmented, irregularly clumped, basophilic material throughout the mid - dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium."]}
{"id": "CaseReportBench:train-415", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}", "questions": ["How is the patient's stature described in the document (e.g., short, tall, average), without providing exact measurements?"], "ground_truth_arguments": ["short stature"]}
{"id": "CaseReportBench:train-587", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What definitive diagnosis was established for the patient after hair and nail analysis?", "Which condition was confirmed by the neutron activation analysis of the patient’s hair and nails?", "What disease was identified as the underlying cause of the patient’s symptoms based on the arsenic level findings?", "What final diagnosis was made that explained both the dermatologic and dental manifestations in this case?"], "ground_truth_arguments": ["chronic arsenicosis"]}
{"id": "CaseReportBench:train-491", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': 'A 12‐year‐old girl, born from consanguineous marriage, was presented with a five‐year progressing bilateral, symmetrical, hyperpigmented, and thickened patches with hypertrichosis. These lesions were present not only in the inner thighs but also in pubic and lumbar regions. On examination, she has gluteal lipodystrophy, swelling with hyperpigmentation of labia majora as well as finger and toe flexion contracture (camptodactyly and hallux valgus), and deformation of teeth (Figure 1 ). Erythematous, annular, and figurate lesions slightly keratotic without atrophy were present in cheeks and nose (Figure 2 ). Dermoscopy revealed multiple telangiectasias drawing a reticulated network (Figure 3 ). A four‐mm punch biopsy showed perifollicular focal para‐keratotic hyperkeratosis of the epidermis. The dermis was slightly edematous and contain ectatic capillaries. There was a lymphocytic and histiocytic infiltrate (Figure 4 ). IHC was positive for CD68 (Figure 5 ). The diagnoses of a mycological cause, porokeratosis of Mibelli, and sub‐acute lupus erythematous were excluded. She has also been explored for hearing loss in the early childhood with hearing aids. Ophthalmological examination showed chorioretinal atrophy. Biological data showed low hemoglobin (9.5 g/dL) and high erythrocyte sedimentation rate (75 mm/h). The rest of laboratory tests including thyroid function tests, lipid profile, liver function tests, renal function tests, and antinuclear antibodies profile were all normal. Echocardiography and electrocardiogram were normal. Abdominal ultrasound found small uterus and ovaries with thickened skin and subcutis of vulva. Genetic analysis revealed homozygous missense mutation c.1088G>A; p.Arg363GIn in exon 6 in linkage disequilibrium with the same non‐pathogenic variant at intron 2 c.300+3A>G. H Syndrome was diagnosed based on histological, immunohistochemical (IHC) examination and molecular analysis. The unusual feature of this case of H Syndrome was the presence of erythematous annular and figurate lesions that were slightly keratotic in cheeks and nose, thus representing a new clinical feature of H Syndrome.'}", "questions": ["Which categories of investigations (e.g., histological, immunohistochemical, molecular) were cited as supporting the case?", "Which types of diagnostic examinations were mentioned as contributing to establishing the diagnosis (such as histology, IHC, or molecular analysis) without requiring detailed findings?"], "ground_truth_arguments": ["H Syndrome was diagnosed based on histological , immunohistochemical ( IHC ) examination and molecular analysis ."]}
{"id": "CaseReportBench:train-248", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 63-year-old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A-C ) was referred to our hospital due to an abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm ( Fig. 1D ). He had a history of hypertension for 5 years and a smoking habit (10 cigarettes/day). Coronary angiography revealed mild to moderate coronary atherosclerotic lesions ( Fig. 1E and F ). He was initially suspected of having FH based on his physical findings as well as the presence of AAA with a modestly elevated LDL cholesterol level (166 mg/dL). He was born to consanguineous parents (second cousins). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis. Recessive inherited disease was speculated at this point, so we investigated his genetic background using whole-exome sequencing, assuming a recessive form of inheritance. The mean depth was 99.9× per base across the whole exome. The percentage of on-target reads was 84.6%. Also, the coverage rate of target coding lesions (10×) was 99.0%. Bioinformatics analyses and segregation pattern matching followed by exome sequencing were performed for the patient to identify causative variants. The number of aligned variants in the patient that passed the standard quality control was 142,508. Of those, 15,335 were missense, nonsense, splice site, and frameshift variants. After removing “common” variants ( 10 ), 3,042 variants were detected. Subsequently, filtering against the segregation pattern assuming the recessive form of inheritance with the use of an in silico annotation prediction tool (scaled C-score >20) reduced the candidate variants to homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene (c.410G>A or p.Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ). Accordingly, an increased serum level of cholestanol was found (5.2 μg/mL, reference range 1.62-3.08). The patient did not show any neuropathy, although T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging showed periventricular white matter. Other classical phenotypes of CTX, such as juvenile cataract, chronic diarrhea, and intellectual disability, were not found. Endovascular repair (EVAR) was successfully performed for the treatment of his saccular type AAA. Atorvastatin 10 mg was used to reduce his LDL cholesterol, although chenodeoxycholic acid was not used due to the lack of neuropathy.'}", "questions": ["What findings were reported on computed tomography regarding the abdominal aortic aneurysm?", "What findings were observed on coronary angiography regarding coronary atherosclerotic lesions?", "What information was provided about the patient's LDL cholesterol level?", "What genetic abnormality was reported in the CYP27A1 gene?", "How was the patient's serum cholestanol level described in relation to normal reference values?", "What abnormalities were observed on T2‑weighted and FLAIR magnetic resonance imaging?"], "ground_truth_arguments": ["Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm", "Coronary angiography revealed mild to moderate coronary atherosclerotic lesions", "modestly elevated LDL cholesterol level ( 166 mg / dL )", "homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene ( c.410G > A or p. Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing", "increased serum level of cholestanol was found ( 5.2 μg / mL, reference range 1.62 - 3.08", "T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) magnetic resonance imaging showed periventricular white matter"]}
{"id": "CaseReportBench:train-132", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case presentation': 'A 50-year-old male with a history of MERRF syndrome was found to have serum prostate specific antigen of 9.45 ng per milliliter on routine screening. His urological history was significant for mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35. There was no erectile dysfunction with a normal International Index of Erectile Function score (24/25). His urinalysis was negative for pyuria or microscopic hematuria. The patient had been diagnosed with a sporadic form of MERRF as an adult after developing symmetric lipomas in his cervical region along with exercise intolerance and mild muscle atrophy. Despite having the common MERRF mitochondrial DNA mutation (A8344G) in his blood with multiple symmetric lipomatosis, his variant of MERFF did not include cognitive impairment nor seizures. 1 His past medical history was significant for a history of hypertension and hypercholesterolemia and his medications included levocarnitine, losartan, hydrochlorothiazide, and metoprolol. His surgical history included a tonsillectomy as a child and plastic surgery to remove neck lipomas. His family history was positive for lung and liver cancer in his mother. His physical examination showed normal vital signs and a body-mass index of 25 (height: 1.65 m, weight: 68 kg). Relevant findings included large, painless, symmetrical cervical lipomas ( Fig. 1 A and B), normal external genitalia, and a digital rectal examination revealing a soft prostate with good lateral definition bilaterally and an estimated volume of 30 cubic centimeters (cc.). A neurological examination was normal except for mild muscle weakness at the end of the day. Fig. 1 (A) Front and (B) lateral images of the patient with MERRF syndrome with characteristic cervical lipomas (with patient permission). Fig. 1 The patient underwent a 12-core ultrasound-guided transrectal prostate biopsy revealing grade group 2 adenocarcinoma (Gleason score 3 + 4 = 7) at the left mid for 9 mm (mm.) and right base for 5.5 mm., and grade group 1 (Gleason score 3 + 3 = 6) at the left base for 9 mm. Perineural invasion was present. His transrectal prostate ultrasound showed a prostate volume of 28.9 cc but no hypoechoic nodules. His calculated PSA density was 0.32 ng/ml/cc. After discussing all the treatment options, the patient chose a radical prostatectomy given his young age, high PSA density, moderate voiding dysfunction, and grade group 2 with significant involvement (9 mm. 5.5 mm., 9 mm.). Since proceeding with surgery was contingent upon neurology clearance, the patient was evaluated by his neurologist with a specialty in mitochondrial disorders. Given that his MERRF variant was only associated with mild myopathy, the patient was cleared for surgery with a willingness to accept a potentially higher risk of complications during intubation given his neck lipomas, as well as a theoretically higher risk of urinary incontinence or erectile dysfunction given the associated myopathy which characterizes the MERRF syndrome. The patient underwent a transperitoneal bilateral nerve-sparing robotic radical prostatectomy and pelvic lymphadenectomy without complications. There were no intubation-related complications; operative time was 150 minutes with an estimated blood loss 50 cc. The patient was discharged on postoperative day 1 without complications nor transfusions and his catheter was removed on postoperative day 7. His prostatectomy pathology was grade group 2, pathologic stage T2 with negative margins and lymph nodes. Based on the EPIC short form questionnaire administered four months after surgery the patient was free of pads and his PSA was less than 0.1. ng/ml. After 6 months, the patient could achieve intercourse with the aid of vardenafil on-demand with an International Index of Erectile function of 20/25. At last follow-up 52 months after surgery, the patient continues to be continent, has satisfactory sexual function using daily tadalafil, and his PSA remains less than 0.1 ng/ml.'}", "questions": ["What cholesterol‑related or dyslipidemia diagnoses are mentioned in the patient's past medical history?"], "ground_truth_arguments": ["hypertension and hypercholesterolemia"]}
{"id": "CaseReportBench:train-584", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["Provide a concise summary of the pelvic imaging results (pelvic examinations, CT scans, and transvaginal ultrasound), indicating which studies were unremarkable and any specific findings such as cysts.", "What did the small bowel follow‑through study reveal?", "What were the initial serum potassium and creatinine values, and how did they compare to their reference ranges?", "Describe the changes in serum sodium, serum osmolality, urine sodium concentration, and urine specific gravity observed during the hospital stay, including the reference ranges for each measurement.", "What abnormalities were identified on the brain MRI, and what diagnosis was suggested by these findings?", "Report the measured urine porphobilinogen level and the 24‑hour urine uroporphyrin level, together with their respective reference ranges, using the exact values as stated in the document."], "ground_truth_arguments": ["Multiple pelvic examinations and 3 computerized tomography ( CT ) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen", "initial laboratory studies showed hypokalemia ( potassium 3.4 mmol / L, reference range 3.5–5.1 mmol / L ), and an elevated creatinine 1.14 mg / dl ( baseline around 0.80 mg / dl ). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit", "serum sodium decreased abruptly from 136 mmol / L to 127 mmol / L ( range : 135–145 mmol / L ). Serum osmolality was low at 271 mOsm / kg ( range : 280–300mOsm / kg ), urine sodium was markedly elevated at 168 mmol / L and urinalysis was remarkable for increased urine specific gravity ( > 1.042 )", "Magnetic Resonance ( MR ) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES", "urine porphobilinogen was measured and was found to be elevated at 188.4 mg / L ( range : 0.0–2.0 mg / L ). 24 - hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr ( range : 0.0–1.5mg/24hr )"]}
{"id": "CaseReportBench:train-267", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Chief complaints': 'Recurrence of abdominal pain, nausea, and vomiting in a kidney transplant patient.', 'Personal and family history': 'The patient had no known family history of porphyria.', 'CASE SUMMARY': 'The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro-pathy. He subsequently developed diabetes mellitus which required insulin therapy. He had been treated in the recent past with local mesalamine for proctitis. He presented with classic but common symptoms of AIP including intense abdominal pain, hypertension, and anxiety. He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained. His urinary postprandial blood glucose level was 60 mg/24 h (normal, < 2 mg/24 h). He was placed on a high carbohydrate diet, and his symptoms slowly improved.', 'Physical examination': 'The patient was hemodynamically stable with a heart rate of 90 bpm and blood pressure of 160/90 mmHg, but appeared in mild distress. The physical examination revealed an intermittently tender, non-distended abdomen with normal bowel sounds and absent rigidity, rebound, and guarding. The remainder of the physical exami-nation was unremarkable.', 'Imaging examinations': 'Plain X-rays of the abdomen showed distended colon and fecal impaction, and ultrasound revealed that the liver, spleen, pancreas, and transplanted kidney were of normal size and consistency and that the site of the left nephrectomy was occupied by intestinal loops.', 'Laboratory examinations': 'Serum levels of hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C-reactive protein were normal, as was the urine analysis. Renal function was stable with a serum creatinine of 1.2 mg/dL; the urine culture was negative.', 'History of present illness': 'A 65-year-old man reported the appearance of rectal blood in March 2017 and visited a proctologist. He started local mesalamine therapy for proctitis, but the drug was discontinued a few days later due to abdominal pain and constipation. During the subsequent 6 mo, he presented several times to the emergency department complaining of severe abdominal pain, nausea, and vomiting. He related an anxious mood and low energy level in addition to tachycardia and an increase in blood pressure which was no longer well-controlled with his usual therapy. He presented to the emergency room eight times for various complaints (Figure 1 ): Epigastric pain without mention of mesalamine, agitation and anxiety, thoracic pain, abdominal pain, and precordial pain.', 'History of past illness': 'The patient had been treated for hypertension since 1994 and developed ischemic heart disease. His renal function gradually deteriorated over the years due to suspected nephroangiosclerosis and chronic interstitial nephropathy, as ultrasound examination demonstrated small echogenic kidneys. He started hemodialysis in 2008 and was evaluated for renal transplantation; a left nephrectomy was performed for a small incidental renal carcinoma. The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis. He underwent a deceased-donor kidney transplant in 2015, for which he was treated with tacrolimus, mycophenolate mofetil, and methylprednisolone. He developed diabetes mellitus post-transplant and insulin therapy was initiated (see Table 1 ).'}", "questions": ["What was the urinary postprandial blood glucose level and its normal reference range?", "What abnormalities were described on the plain abdominal X‑ray and what did the abdominal ultrasound show regarding the colon, fecal impaction, liver, spleen, pancreas, transplanted kidney, and the left nephrectomy site?", "Which serum laboratory tests were reported as normal, and what were the reported serum creatinine value and urine culture result?", "What did the ultrasound examination of the native kidneys reveal about their size and echogenicity?", "What histopathologic findings were identified in the left nephrectomy specimen?"], "ground_truth_arguments": ["His urinary postprandial blood glucose level was 60 mg/24 h ( normal, < 2 mg/24 h", "Plain X - rays of the abdomen showed distended colon and fecal impaction, and ultrasound revealed that the liver, spleen, pancreas, and transplanted kidney were of normal size and consistency and that the site of the left nephrectomy was occupied by intestinal loops. ', ' Laboratory examinations ' : ' Serum levels of hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C - reactive protein were normal, as was the urine analysis. Renal function was stable with a serum creatinine of 1.2 mg / dL; the urine culture was negative. '", "ultrasound examination demonstrated small echogenic kidneys", "The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis"]}
{"id": "CaseReportBench:train-394", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Cases': 'The older patient was 20 years old. She was a product of a full-term spontaneous vaginal delivery at home. She was found to have severe virilized external genitalia: a phallic-like structure with hypospadias and incompletely fused labioscrotal folds. She was raised and named as a boy and no medical advice was sought at that time. Her parents reported that she had behaved as a female since early childhood. She was interested in playing with girls and in girl’s games, although she studied at male schools. She spent most of her time with her girlfriends and felt most comfortable when she dressed as a female. She was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation. Physical examination showed a short male-looking adolescent with acne and Tanner stage IV breast development. Her height was 133 centimeters. Her blood pressure was 140/88. Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An adrenocorticotropic hormone (ACTH) stimulation test showed a baseline cortisol (F) level of 28 nmol/L, ACTH of 201 ng/mL (normal, 0–46), 11-deoxycorticosterone (11-DOC) of 20 nmol/L (normal, 0.49–3.3), 17-hydroxyprogesterone (17-OHP) of 17 nmol/L and testosterone (T) of 7 nmol/L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol/L, the 11-DOC level was 141 nmol/L (normal, 2.2–6.8) and the 17-OHP level was 22 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X-ray. Examination under anaesthesia combined with cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus. Based on her biochemical and radiological evaluation, she was diagnosed as having 11-hydroxylase deficiency and was started on hydrocortisone 10 mg twice a day. She was evaluated by the pediatric psychiatrist who clearly confirmed her female gender identity and her strong wish to be converted to a female. Feminizing genitoplasty (clitoral reccesion) was performed at the age of 16 years and she was given a female name. She admitted her strong desire to get married and to be a mother. The younger patient was 16 years old. He was born at home and raised and named as a boy based on the appearance of the external genitalia. His parents reported that he behaved as a male and was proud of that. He was interested in playing with boys and in boy’s sports. He was dressed as a boy and had a short haircut. He was referred to our clinic at the age of 13 years. Physical examination showed a short stature, a masculine appearance, acne and Tanner stage IV pubic hair and stage II breast development. His height was in the fifth centile. His blood pressure was 130/80 mm Hg. Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol/L, an ACTH of 231 ng/mL, 11-DOC of 40 nmol/L, 17-OHP of 18 nmol/L and a T level of 7 nmol/L. Sixty minutes after ACTH stimulation, the F level was 45 nmol/L, 11-DOC was 114 nmol/L and 17-OHP was 20 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years. He was diagnosed as having 11-hydroxylase deficiency and started on hydrocortisone 10 mg twice a day. His final height was 139 centimeters. He was interviewed by the pediatric psychiatrist who clearly confirmed his male gender identity and his strong wish to continue to be raised as a boy. We had several separate meetings with him and his parents and informed them that he would be an infertile man if he decided to continue to be raised as a man and there was a possibility that he would be a fertile women if he converted to his genetic sex. The patient, however, refused to change to his female genetic sex and admitted his strong wish to be a man forever. After more that one year of counseling and intensive psychiatric interview, he and his parents decided on a hysterectomy “to avoid menarche which might affect him psychologically” as his mother said. Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed. Both patients were satisfied by the way they were managed and raised and there were no postoperative psychological complications.'}", "questions": ["What is the age of the older patient described in the case?"], "ground_truth_arguments": ["20 years old"]}
{"id": "CaseReportBench:train-135", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["What feeding difficulties did the infant exhibit?", "What were the findings of the respiratory and abdominal examinations?"], "ground_truth_arguments": ["poor feeding", "Examinations of the respiratory system and abdomen were within normal limits"]}
{"id": "CaseReportBench:train-159", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case 2': \"The second case was of a 28-year-old male who was born of a non-consanguineous marriage, had delayed psychomotor milestones with mental retardation, congenital cataract, and recurrent episodes of diarrhea since early childhood. He had history of progressive spastic diplegia, tremulousness in both upper limbs and scanning speech. The patient had impaired attention, vigilance, comprehension, and new learning ability. Pan-sensory impairment was noted below knee with impaired limb coordination in upper limbs. Patient's skin biopsy of swelling over Achilles confirmed xanthoma. MRI brain showed altered signals in bilateral cerebral peduncles, ventral pons, both the middle cerebellar peduncles and medullary pyramids. Based on the clinical, radiological, and biopsy findings of the Achilles tendon swelling, diagnosis of CTX was confirmed.\", 'Case 1': 'A 50-year-old commerce graduate with degree in law presented to us with insidious onset gradually progressive spastic diplegia for 20 years followed later by gradually progressive bladder dysfunction, poor scholastic performance, and a single seizure. He was born to non-consanguineous parents and had unremarkable early psychomotor development. Pedigree analysis revealed absence of any family history in previous two generations. On examination, patient had thoracic kyphosis with contractures at hip, knee, and ankle joints. He had firm, non-tender swellings over ankles, patella, and elbows bilaterally. Detailed higher mental function assessment revealed impairment of attention, new learning and visual memory with normal language functions. His speech was slow and slurred but could be comprehended with little difficulty. All cranial nerve functions were intact. The patient had severe spasticity in both lower limbs with brisk deep tendon reflexes in both the upper and the lower limbs, extensor plantar responses, and normal sensory examination. Blood investigations revealed a normal complete hemogram (including hemoglobin, total leukocyte count, differential leukocyte count), liver and kidney function tests, serum electrolytes and, triglyceride and cholesterol levels. X-rays of ankle, knee, and elbow showed homogenous soft tissue swelling. MRI brain showed T2-weighted hyperintensities in dentate nucleus regions bilaterally and generalized cerebral and cerebellar atrophy. Plasma cholestanol levels were found to be raised suggesting cerebrotendinous xanthomatosis. The genetic analysis of CYP27A1 gene of the patient was carried out by the method of Polymerase Chain Reaction and sequencing of both the DNA strands was done. The analysis revealed heterozygous mutation in exon 6 with substitution of cytosine by thymine at 1151 position (c. 1151C > Tp.P384L) and a novel mutation in exon 1 of CYP 27 gene with substitution of thymine by cytosine at nucleotide position 2 of the gene (c. 2T > Cp.M1T). The mutation in exon 6 is already described as disease causing while the mutation in exon 1 is previously unreported as per the current Human Gene Mutation Database. The mutation causes loss of a highly conserved start codon and likely results in loss of functional protein. The patient is receiving atorvastatin besides physical therapy and chenodeoxycholic acid (CDCA) is being arranged as it is not marketed in India.'}", "questions": ["What recurrent gastrointestinal manifestations were reported in the cases?"], "ground_truth_arguments": ["recurrent episodes of diarrhea"]}
{"id": "CaseReportBench:train-75", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE PRESENTATION': 'A 20-year-old male presented with a gradually increasing swelling of the left testis for 1 year duration. He was otherwise asymptomatic. He was diagnosed to have CAH at the age of 1 year but had defaulted treatment at the age of 4 years. The patient had a strong reluctance to seek medical care due to his poor socioeconomic status and fear of receiving an unfavourable prognosis. Genital examination revealed a large hard indurated swelling of both epididymes more prominent on the left side. Left testis was ill-defined with an approximate diameter of 3.5 cm. Ultrasonography showed bilateral enlargement of the testes and epididymes (right testis measuring 41 ml in volume (6.6 cm × 3.7 cm × 2.3 cm), left testis measuring 52.1 ml in volume (6.2 cm × 4.5 cm × 3.6 cm)). In addition, there were bilateral grade-II varicocele. Seminal fluid analysis showed azoospermia. A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma (Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent (Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin (Fig. 3 ). Thus, the histopathological analysis was more in favour of TART rather than Leydig cell neoplasm. A course of prednisolone was started and there was good response. In 6 weeks, there was marked reduction in the sizes of testes with minimal induration. He was followed up for 6 months but was eventually lost to follow up.'}", "questions": ["What was the patient's age at the time of presentation?"], "ground_truth_arguments": ["20 - year - old"]}
{"id": "CaseReportBench:train-31", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}", "questions": ["What type of genetic test was used to confirm the diagnosis of cerebrotendinous xanthomatosis in this patient?", "What finding in the diagnostic work‑up established that the patient had CTX?"], "ground_truth_arguments": ["CYP27A1 gene sequencing confirmed the diagnosis of CTX .", "confirmed CTX diagnosis ."]}
{"id": "CaseReportBench:train-182", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'CASE PRESENTATION': \"Following the complaints of other players over a 14 - year old girl with male phenotype in the under 16 age- group of women's national soccer team, further evaluation about her condition was performed by the team physician. In her general appearance, she had hirsutism, increased muscle bulk, dark skin, voice deepening and short stature. In her physical examination her specifications were as below: height: 145 cm, weight: 46 Kg, body mass index (BMI): 21.8, Tanner staging: 1 ( Fig. 1 ), lack of menstrual period, clitoral enlargement, good strength and excessive fatigue after exercise. In her past medical history, following her family's concern about her ambiguous genitalia, she underwent a number of specific laboratory tests and chromosomal karyotype and based on hormonal assessment the final diagnosis was Congenital Adrenal Hyperplasia (C.A.H) due to 21 hydroxylase deficiency. Afterwards, she had undergone surgery (vaginoplasty) when she was 3 years old and also she had been admitted in hospital 2 times because of electrolytes imbalance. In her drug history, she had been using 30 mg hydrocortisone daily in three divided doses (15.8 mg/m 2 ·d) plus 100 mg fludrocortisone daily in 2 divided doses, but recently her drug doses had been changed to 7/5 mg prednisolone in the morning and 5 mg at night. In her sports career, she used to be in First Division League of indoor soccer for 4 years and she was also selected in preparation training camp of women football team for Singapore's youth Olympic Games. She plays as a striker. She is a speedy player with a high level of technique. Despite her impressive role in the team, she usually cannot play more than one halftime because of excessive fatigue and vomiting due to electrolytes imbalance. As her karyotype was XX, based on the IOC (International Olympic Committee) rules, there was no limitation for her participation in international competitions of women. However, following consultations with the TUE (Therapeutic Use Exemption) Committee of games organization, she received TUE to use corticosteroid only within the games period. Now, mainly because of some problems in her medical conditions including prolonged dysfunction due to her ankle sprain, she is playing in the Second Division League of indoor soccer. Because of her irregular check-ups, there isn't much laboratory tests available. Her most recent one, requested by the team physician is shown in the Table 1 .\", 'Case Presentation': \"The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia. She plays in the women's national soccer team of under 16. She has been in the first division league of indoor soccer for 4 years and was also selected in the preparation training camp of women's football team for Singapore's youth Olympic Games. Her illness and dependence on corticosteroid have caused some concerns for her participation in the international competitions of women. However, following consultations with the Therapeutic Use Exemption (TUE) Committee of games organization, she received TUE to use corticosteroid only within the games period. Despite all her problems, she is now playing in the Second Division League of indoor soccer.\"}", "questions": ["Is the patient's muscular strength reported as normal, reduced, or increased?", "Is the patient's fatigue after exercise described as mild, moderate, or severe?"], "ground_truth_arguments": ["good strength and excessive fatigue after exercise"]}
{"id": "CaseReportBench:train-279", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Diagnoses:': 'The proband underwent a thorough examination in our hospital and was diagnosed as mitochondrial encephalomyopathy. The proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene. Although his parents did not carry the mutation.', 'Case presentation': \"The proband was a 12-year-old boy on first visiting to our hospital. The proband was the first and the only child of his healthy, nonconsanguineous parents of Han Chinese descentand was born at 38 weeks gestation by spontaneous delivery. The proband had no postnatal adaptation, and the Apgar score was unknown. He was admitted to the hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after the treatment of unexplained fever and somnolence. The highest temperature was 37.8°C, accompanied by vomiting 4 to 5 times on the same day, with insufficient spirits. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of our hospital (no. 2018021). Informed written consent was obtained from all participants prior to their enrollment in this study. The proband underwent a thorough examination in our hospital, including electroencephalogram, echocardiogram, electrocardiogram, brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), physical examination, laboratory examination, and mitochondrial gene detection. Genomic DNA from the family was extracted from peripheral whole blood samples using the genomic DNA extraction kit (Qiagen) according to the manufacturer's instructions. The entire mitochondrial genomes of the family were PCR amplified in 24 overlapping fragments by using sets of the light strand and the heavy strand oligonucleotide primers, as described elsewhere. Each fragment was purified and subsequently Sanger sequencings were conducted by TSINGKE Biological Technology(Beijing, China). The resultant sequence data were compared with the revised consensus Cambridge sequence (GenBank accession no. NC-012920). His electroencephalogram showed clear increase of 4–5c/s theta waves, 2–3c/s delta waves, with a small amount of sharp waves. His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right (Fig. 1 A). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS (Fig. 1 B). Normal structure and ejection fraction were observed via echocardiography. Serum lactate dehydrogenase, creatine kinase, α-hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range. Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation (Fig. 2 ). The patient was treated according to the diagnosis of mitochondrial encephalomyopathy. Intravenous acyclovir, ceftriaxone and dexamethasone were used for antiviral, antimicrobial, and anti-inflammatory therapy, respectively. Intravenous mannitol was gradually tapered for reducing intracranial pressure with furosemide for inducing diuresis. Intravenous arginine could help to treat alkalosis and supple some essential amino acids. Oral oxiracetam capsules, vitamin B1, and coenzyme Q10 were used for providing nutrition and improving energy. His medications were 30 mg vitamin B1, 0.1gm vitamin C and mecobalamin 750 μg daily after discharge from our hospital. The patient was able to walk and talk slowly with improved writing skills and no stroke-like episodes. The neurological examination was negative and muscle tension was identified as grade V.\", 'Patient concerns:': \"A 12-year-old boy was admitted to Shaoxing People's Hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after treatment of unexplained fever and somnolence.\"}", "questions": ["Did the patient experience vomiting on the day of the fever?"], "ground_truth_arguments": ["vomiting 4 to 5 times on the same day,"]}
{"id": "CaseReportBench:train-294", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case report': 'We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. The Saudi female patient in the UK developed recurrent bouts of abdominal pain, nausea, and vomiting during first pregnancy, diagnosed as hyperemesis gravidarum, and was treated with IV fluids and antiemetics. There was improvement in the condition and the patient delivered a healthy child (in Saudi). After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatremia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities. She was intubated for 3 days. Initial postextubation, physical examination result was unremarkable except for unexplained behavioral disturbances and lower limb weakness. Initial instigations showed sodium levels ranged between 118–125 mmol/L (135–144 mmol/L), mildly elevated transaminases (aspartate aminotransferase/alanine transaminase), and slight elevation of anti-neutrophil antibodies of the perinuclear type (P-ANCA). Alkaline phosphatase, bilirubin, complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid (CSF) analysis findings were all within normal range. The abdominal imaging result was normal, except for contracted gallbladder and stones. Urine became dark red on exposure to light. Total porphyrins in urine were elevated: 29,100 nmol/24 hours (normal: ≤214), with main elevation in uroporphyrin level, 24,200 nmol/24 hours (normal: ≤30), and mild elevation in coproporphyrin level, 118 nmol/24 hours (normal: ≤38). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene (c. 760delC p.L254X). The patient was treated with intravenous heme arginate (4 mg/kg/day) for 5 days, that was followed by an improvement in the chemical and clinical parameters.'}", "questions": ["What were the observed changes in the patient's blood pressure during the acute episode?", "What heart rate abnormalities were reported in the patient?"], "ground_truth_arguments": ["elevated and uncontrolled blood pressure, sinus tachycardia"]}
{"id": "CaseReportBench:train-13", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'A 12-year-old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days. On physical examination the child was found to have retarded growth (dwarfism) and a pendulous abdomen. Per abdominal examination revealed hepatomegaly. USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm–sized, well-defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well-circumscribed, low-attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted. Hepatomegaly with diffusely low attenuation of liver, bilateral renal calculi (which hinted at hyperuricemia – a known feature of von Gierke disease), clinical features of dwarfism, facial dysmorphism, and protuberant abdomen, were all features that favored the diagnosis of von Gierke disease. Moreover, in the pediatric age-group, liver tumors are rare and hepatic adenoma occurs almost exclusively in patients with underlying von Gierke disease. CT scan features like well-circumscribed margins, subcapsular location, and contrast enhancement also supported the diagnosis of hepatic adenoma. Based on these CT scan findings and clinical features, a probable diagnosis of hepatic adenoma in a case of type Ia glycogen storage disease (von Gierke disease) was suggested. Preoperative laboratory evaluation revealed increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits. The patient was operated and the mass in the liver was surgically resected. The specimen was sent for histopathological examination along with a small bit of liver tissue, which showed PAS-positive glycogen-rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma.'}", "questions": ["Are there any abnormalities in the patient's stature or growth pattern?"], "ground_truth_arguments": ["retarded growth ( dwarfism )", "clinical features of dwarfism"]}
{"id": "CaseReportBench:train-588", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case report': 'An 11-year-old male had presented to the hospital with a history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4-5 years. There was no history of fever or localized pain. On examination, the blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg (75th-90th centile) and his height measured 138 cm (50th centile). Generalized skin hyperpigmentation was present. Systemic examinations were normal. Local examination revealed bilateral scrotal swelling with normal-appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia (testis length 3.5 cm, penile length 10 cm) and stage 3 for pubic hair. The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size (right and left testicular volume – 2.9 mL and 2.8 mL respectively) with multiple well-defined round to oval hetero-echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B). On screening abdominal sonography, a large well-defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity ( Figs. 3 A and B). Based on these findings, the possibility of testicular malignancy with adrenal metastasis was considered. Contrast-enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands (left>right) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C). Serum tumor markers (alpha-fetoprotein, LDH, and Beta hCG) were negative hence, the diagnosis was reconsidered for the possibility of testicular adrenal rest tumors in an undiagnosed case of congenital adrenal hyperplasia. Fig. 1 (A) Grayscale US of scrotum showing normal-sized right testis with heterogeneous appearance. (B) US image of bilateral testes with multiple nodules containing tiny calcific foci (black arrow). Fig 1 Fig. 2 (A) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. (B) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 (A) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions (white arrow). (B) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions (white arrow). Fig 3 Fig. 4 (A) Contrast enhanced computed tomography (CECT) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia (White arrows). (B) CECT pelvis axial section showing multiple enhancing nodules in the right testis (black arrow). (C) CECT pelvis axial section showing multiple enhancing nodules in left testis (black arrow). Fig 4 X-ray left wrist AP/lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq/L (normal range: 3.5-4.5 mEq/L), whereas the sodium level remained within normal limits at 140 mEq/L. There was a significantly heightened level of 17-hydroxyprogesterone at 1800 ng/dL (normal range: <110 ng/dL), accompanied by normal levels of lactate dehydrogenase (LDH), beta-human chorionic gonadotropin hormone (B-HCG), and alpha-fetoprotein (AFP). Additionally, the serum adrenocorticotropic hormone (ACTH) concentration was elevated, measuring 564 pg/mL (normal range: 7.2-63.3 pg/mL), while cortisol levels were diminished, measuring 5.7 µg/dL (normal range: 7-25 µg/dL). Dehydroepiandrosterone sulfate (DHEA-S) was measured at 5.25 µmol/L (normal range: ≤ 3.726 µmol/L), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng/dL (normal range: 31-65 ng/dL), and there was a reduced level of Inhibin B, measuring 71.1 pg/mL (normal range: 240-445 pg/mL). Collectively, these findings point towards a diagnosis of congenital adrenal hyperplasia. The patient is currently undergoing treatment with hydrocortisone and is on regular follow-up. The 3-month follow-up revealed clinical improvement with a reduction in testis size and decreased ACTH levels, indicating positive progress. Fig. 5 X-ray of left wrist AP and a lateral view showing accelerated bone age corresponding to approximately 18 years. Fig 5', 'Patient consent': 'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.'}", "questions": ["What symptom(s) indicating abnormal heart rhythm are reported in the case?"], "ground_truth_arguments": ["palpitation"]}
{"id": "CaseReportBench:train-4", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}", "questions": ["What disorder was diagnosed in the patient?", "How was the diagnosis of this disorder confirmed?", "What category of genetic abnormality was identified that contributed to the diagnosis?"], "ground_truth_arguments": ["Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations ."]}
{"id": "CaseReportBench:train-123", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Presentation of case': 'The case was a 65-year-old female with VDRR who reported progressive weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm. Imaging studies demonstrated cord compression with ectopic ossification at the rim of the occipital bone and OPLL at C1 level. Ankylosis of the whole spine below the C2 vertebra was also noted with preserved mobility only at the craniovertebral junction. The patient was first referred to our hospital because of difficulty in walking at the age of 34, when she was diagnosed with VDDR. Later, the diagnosis was genetically confirmed as described by a different research group . The patient had previously undergone T7–T9 laminectomy due to thoracic myelopathy at another hospital at the age of 24, after which her myelopathic symptoms subsided for 7 years. At the age of 34, she underwent a second posterior decompression surgery (T4–T9) for gait disturbance due to thoracic myelopathy after a diagnosis of OPLL and OYL, which resulted in improvement of her symptoms. Since then, the patient has been followed-up on annual basis and remained functionally stable for over 30 years. At the age of 65, she reported weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm. She was admitted for further investigation and treatment. On admission, she was 118 cm tall with a marked round back and bowed legs. She was able to walk only short distances supporting herself on a wall. Neurologic examination revealed decreased light touch and pinprick sensation, and motor weakness (3/5 strength) in the distal upper extremities. The grip power was 6 kg in both hands. Tendon reflexes were equivocal with indifferent Babinski sign bilaterally. Plain radiograph showed marked kyphosis of the thoracic spine (T1–T12 angle; 94°) ( Fig. 1 ). Computed tomography demonstrated ankylosis of the whole spine below the C2 vertebra with extensive ossification of the paraspinal ligaments ( Fig. 2 A, B). In contrast, decreased but preserved mobility (9° on flexion and extension) was noted at the craniovertebral junction (CVJ). No overt radiographic instability was found in the atlantoaxial region, with an atlantodental interval of 1 mm. In addition, there was ossification at the rim of the occipital bone, and OPLL at the C1 level. Magnetic resonance imaging (MRI) revealed spinal cord compression at the levels of both the occipital bone and C1 ( Fig. 3 ). The patient underwent posterior decompression, in which the posterior arch of C1 and the ossified rim of the occipital bone were resected. Deformation of the dural sac was observed at locations corresponding to the resected portions of the rim of the occipital bone and C1 posterior arch, indicating that there had been sustained pressure on the sac. Her postoperative course was uneventful. At the 18-month follow-up visit, the patient was free of pain and numbness. Her grip power had improved to 20 kg in the right and 15 kg in the left hand. She had regained the ability to walk with the support of a cane.', 'Patient consent': 'Informed consent was obtained from all individual participants included in this study.'}", "questions": ["What type of rickets was initially identified in the patient?", "What was the later genetically confirmed diagnosis of rickets reported in the case?"], "ground_truth_arguments": ["VDRR", "diagnosed with VDDR"]}
{"id": "CaseReportBench:train-371", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What type of cerebral infarction was observed on the brain MRI/MRA, and was there any elevation in blood lactic acid noted?", "What specific mitochondrial DNA mutation was detected by PCR sequencing?", "What electrolyte and metabolic abnormalities were noted in the pre‑operative laboratory results?", "What were the findings of the pre‑operative chest X‑ray?", "What arterial blood gas, electrolyte, and glucose findings were observed after induction of anesthesia?", "What arterial blood gas, electrolyte, glucose, and lactic acid findings were recorded in the recovery room prior to transfer to the ward?"], "ground_truth_arguments": ["In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered ( 7.54 mM / L ).", "adenosine - to - guanine transition at t - RNA nucleotide 3243 in PCR sequencing", "The laboratory results showed hyponatremia ( 126 mEq / L ), hyperglycemia ( 257 mg / dl ), and light metabolic acidosis ( pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM / L, BE -5.3 mM / L )", "There were no abnormal findings in the chest X - ray", "Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM / L, BE -2.1 mM / L; her electrolytes were Na + 125 mEq / L, K + 3.8 mEq / L, Cl - 88 mEq / L; and her blood sugar was 176 mg / dl", "The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM / L, and BE -3.6 mM / L; her electrolyte levels were Na + 128 mEq / L, K + 4.1 mEq / L, and Cl - 90 mEq / L; and her blood sugar level was 120 mg / dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM / L."]}
{"id": "CaseReportBench:train-130", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'2. Case presentation:': 'A 13-year-old girl with no history of medical or familial diseases presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache, which had started 10 days ago. Within the next few days following admission, the patient developed an attack of generalized tonic-clonic seizure associated with low-grade fever. On examination, the patient was confused in post ictal state. Otherwise, the neurological and general examination was unremarkable. Patient was hemodynamically stable. Urgent brain computed tomography (CT) scan showed brain edema ( figure 1 ). Cerebrospinal fluid (CSF) analysis, routine blood chemistry tests, blood culture, and serum electrolyte evaluation were performed. On a clinical basis, central nervous system infection was suspected and the patient started to receive acyclovir. Due to severe abdominal pain, abdominopelvic CT scan with contrast was done, which revealed marked distention of large bowel, and no definite air-fluid level or obstructing masses ( figure 1 ). The initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level: 108 milliequivalents per liter (mEq/L), potassium level: 2.7 mEq/L, total calcium level: 4.9 mg/dl, ionized calcium level: 3.5 mg/dl, magnesium level: 0.7 mEq/L, and phosphorus level: 2.1 mEq/L ( table 1 ). Within the next few days, the patient began to become agitated and developed generalized muscle pain despite proper correction of resistant hyponatremia with hypertonic saline 3%. In addition, the patient started to develop polyuria, and polydipsia, despite the normovolemic state, confirmed by clinical examination and central venous pressure monitoring. High suspicion to Bartter-like syndrome was raised as the renal tubular defect with increased renal loss of electrolyte was confirmed by the following laboratory investigation: urine osmolarity 277mOml/kg, serum osmolality 252 mmol/kg, serum chloride 73 mEq/L, and urinary Calcium/creatinine ratio 1.053 ( table 1 ). Within the next few days, she developed weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic. The rest of the examination was normal. Our opinion about the case changed and we had a rising concern about genetic disease. At that time, the whole-exome sequencing was sent abroad to CENTOGENE GmbH (Rostock, Germany) for genetic analysis. Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy (prolonged first time (F) wave latencies with reduced amplitude of compound motor action potentials). Unfortunately, the condition worsened till the patient became intubated and mechanically ventilated due to respiratory muscle involvement. The CSF examination showed cytoalbuminous dissociation, and this made the diagnosis more in favor of Guillain-Barre Syndrome (GBS). The patient received intravenous immunoglobulin (IV IG) (2gm per Kg divided over 5 days) with partial improvement. Due to the failure of multiple trials for weaning from mechanical ventilation, tracheostomy was performed. Genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase (HMBS) gene, which confirmed the diagnosis of autosomal dominant AIP ( figure 2 ). The patient received dextrose 25% and 2 doses of hemin 250 mg once daily for four days, 2 weeks apart followed by another dose after 2 months. There was a marked improvement regarding the weakness, and abdominal pain, and we managed to wean her from mechanical ventilation.'}", "questions": ["What headache symptoms did the patient experience?", "Describe the seizure event, specifying its type and characteristics.", "What was the patient's mental status after the seizure, and were any other neurological findings noted on examination?", "Were any notable abnormalities reported on the urgent brain CT scan?", "What signs of agitation or behavioral changes were observed during the hospital stay?", "What muscle weakness was reported, including any initial locations or overall presence?", "Detail the progression and distribution of muscle weakness, including which limbs were affected and any evolution to quadriplegia.", "What abnormalities were identified on the electrophysiological studies?", "Were there any respiratory complications observed during the hospital stay?", "What abnormalities were found in the cerebrospinal fluid analysis?"], "ground_truth_arguments": ["headache", "an attack of generalized tonic - clonic seizure", "confused in post ictal state. Otherwise, the neurological and general examination was unremarkable", "Urgent brain computed tomography ( CT ) scan showed brain edema", "began to become agitated", "weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic", "Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy ( prolonged first time ( F ) wave latencies with reduced amplitude of compound motor action potentials", "respiratory muscle involvement", "The CSF examination showed cytoalbuminous dissociation", "weakness"]}
{"id": "CaseReportBench:train-212", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': 'A 52-year-old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene. Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme. We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme. After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What ocular condition related to intraocular pressure is noted in the patient's history?", "What corneal and conjunctival abnormalities are present in the right and left eyes at initial presentation?", "Which ocular symptoms did the patient report, including sensations and changes in visual acuity?", "How were the patient's visual acuity and intraocular pressure described in the examination?", "What slit‑lamp examination findings were reported for the patient?", "What changes in ocular discomfort and clinical signs were observed after treatment?"], "ground_truth_arguments": ["glaucoma", "central corneal conjunctivalization of the right eye ( OD ) and the onset of inferior conjunctivalization of the left eye ( OS ). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes ( OU", "visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6 mm Hg. On slit - lamp examination, the patient presented tear break - up time ( TBUT ) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation ( grade III ) in the Oxford Squeme", "reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal ( grade I ) in the Oxford Squeme"]}
{"id": "CaseReportBench:train-88", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'We report on a 5-year-old girl with a history of pink-stained urine as a newborn. Disease onset occurred in the tenth month of life. Her deciduous teeth sprouted with a red-brown color. She also suffered from episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation (fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas. Spleen enlargement was also observed. Urine porphyrins were extremely elevated to 16 μmol/dl with a predominance of coproporphyrins and uroporphyrins. However, the detailed concentration of each porphyrin was not analyzed. Severe cutaneous photosensitivity, blistering of light-exposed skin, history of pink-stained diapers and accumulation of porphyrins in the blood and various other tissues, particularly erythrodontia (fig. 1b ), suggested the diagnosis of CEP. The clinical and biochemical data of the patient are summarized in table 1 . With strict avoidance of UV and visible light, use of topical sunscreen, oral treatment with β-carotene and antibiotic for preventing bacterial infection of the skin, the bullae healed, leaving milia and hyperpigmented scars without the need of a blood transfusion. Mutation analysis of the UROS gene of the patient with CEP was performed. The DNA of exons 2–10 including splicing junctions of all exons was amplified by PCR and then sequenced. A single missense mutation corresponding to a G-to-T transversion (11,776 g>t) in exon 2 was found, leading to an amino acid change from valine at position 3 to phenylalanine (fig. 2 ). The result indicated that the patient was homozygous for this mutation. Then, we also analyzed the UROS genes of her parents who were shown to be heterozygote carriers of this mutation (fig. 3 ). Her brother had died of a disease similar to hers in terms of symptoms and abnormalities, suggesting that he had the same gene mutation (V3F). Conversely, on the basis of the pedigree analysis spanning three generations, no other symptomatic patients were found. To confirm the genotype-phenotype relationship, we constructed a pET-duet vector carrying mutated cDNA of UROS and transformed it into an Escherichia coli BL21 strain. The expression of UROS in bacteria was induced at 25°C. After purification of the expressed enzyme with nickel ion-beads (Qiagen Inc., Valencia, Calif., USA), the activity of mutated UROS (V3F) was compared with that of normal enzyme by the method of Wright and Lim. The specific activity of the mutated UROS was less than 16.1% that of the control.'}", "questions": ["What class of inborn errors of metabolism is discussed in the case report?"], "ground_truth_arguments": ["CEP"]}
{"id": "CaseReportBench:train-137", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'CASE REPORT': \"A young stocky built adult patient appearing in early twenties dressed in shirt and pant with a thick moustache and beard accompanied with parents walked inside psychiatry out-patient department (OPD) with a referral from plastic surgery OPD concerning gender affirmation surgery. Patient introduced self in a husky masculine voice as Ms. T, a 21-year old female patient and expressed desire to be named as Mr. T, in further conversation. On interview, parents reported patient to be their eldest daughter born of a non-consanguineous marriage following a full term normal vaginal delivery. Parents reported since early childhood, patient was tomboyish, more comfortable playing with boys, watching wrestling and never showed interest in dolls or playing with younger sister or girls at school. Patient used to wear shirt and skirt to school, but at home used to prefer wearing T-shirt and jeans. From adolescence onwards, patient started to gain weight, developed hirsutism and never attained menarche. Mother had to frequently remove patient's facial hairs by hair removing cream. Patient started to feel attracted towards females though never had any sexual contact. Patient started to develop strong disliking towards self being called as a female, withdrew self from female friends and interest in studies declined; but never verbalised these feelings to anyone. 17 years onwards, after completing high school patient started to express strong resentment. Thereafter, with parents consent patient started to dress as males, stopped removing facial hairs. From 18 years onwards, proclaiming self as Mr. T patient started to work as a salesman. Patient and parents were happy with the new desirable identity. Difficulties faced were using common urinals, feeling ashamed of getting the anatomical sex being disclosed and inability to study further or procure a white collared job because of high school certificate mentioning sex as female. Despite these problems, patient was more comfortable in male gender role and since past 2 years, started seeking help for gender affirmation surgery. Patient appeared to be of average intelligence and had no persistent aggressive, violent or criminal tendencies. There was no past history of taking any hormones exogenously. Examination revealed 65 kg weight, 160 cm height and 116/82 blood pressure. External body habitus was of male and external genitalia was of female. There were no apparent cushingoid features. Karyotyping showed 46XX pattern. Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X-ray were normal. Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17-OH progesterone and dehydro-epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test suggesting diagnosis of non-classical congenital adrenal hyperplasia.\"}", "questions": ["Describe the patient's level of intelligence and any reported aggressive, violent, or criminal behaviors."], "ground_truth_arguments": ["average intelligence and had no persistent aggressive, violent or criminal tendencies"]}
{"id": "CaseReportBench:train-38", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["Which routine baseline investigations (e.g., hemogram, blood sugars, liver and kidney function, chest X‑ray, electrocardiography, electroencephalography) were performed and what were their results?", "What were the findings of the cerebrospinal fluid analysis, urine Watson–Schwartz test, electrolyte screening (including serum sodium, phosphate, and potassium), abdominal ultrasonography, and serum lead level?", "What were the cardiac enzyme results, and what did the transthoracic echocardiography reveal about pericardial calcification, mitral valve and papillary muscle involvement, as well as serum calcium and phosphorus levels and the tracheal tube aspirate for acid‑fast bacilli?"], "ground_truth_arguments": ["Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X - ray, electrocardiography, electroencephalography were normal", "Cerebrospinal fluid analysis was normal. Urine Watson – Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia ( serum sodium 126 mmol / L ). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits.", "Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium ( 10.8 mg / dl ) and phosphorus levels ( 5 mg / dl ) were within normal limits. Tracheal tube aspirate for acid - fast bacilli was negative"]}
{"id": "CaseReportBench:train-451", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory. Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE. Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium. The patient is being followed up and has been specifically instructed to report if she becomes pregnant.'}", "questions": ["What were the findings of the routine hemogram, biochemical parameters (including renal function tests and serum calcium), chest X‑ray, and electrocardiogram for the patient?", "What result was obtained from the fecal occult blood test?", "What histological findings were reported in the skin biopsy?"], "ground_truth_arguments": ["The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X - ray and EKG were also normal", "The feces was negative for occult blood", "Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid - dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium"]}
{"id": "CaseReportBench:train-104", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case report': \"A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency.\"}", "questions": ["What feeding difficulties did the patient have during the first week of life?"], "ground_truth_arguments": ["poor feeding by breast and bottle"]}
{"id": "CaseReportBench:train-359", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["What is the patient's age decade?"], "ground_truth_arguments": ["her 40s", "in her 50s", "her 30s"]}
{"id": "CaseReportBench:train-263", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': \"A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.\", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}", "questions": ["What finding was observed on Wood's lamp examination of the patients' urine?", "What symptom involving the diaper was reported in the case description?"], "ground_truth_arguments": ["Wood 's lamp examination revealed pink - red fluorescence of the urine", "red discharge in her diaper"]}
{"id": "CaseReportBench:train-208", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case presentation': 'A known case of hypertension, asthma and AKU presented to Urology clinic complaining of severe LUTS: obstructive symptoms including poor stream, straining, hesitancy, and incomplete emptying of urinary bladder, in addition to irritative symptoms including frequency, urgency and nocturia. These symptoms started 2 months prior to his current presentation with a history of passing stones during urination and acute urinary retention that was relieved by suprapubic catheterization and cystolitholapaxy for his urinary bladder stones. He also reports blackish discoloration of his urine and history of recurrent urinary tract infections (UTIs). On examination, a urethral stone was felt in the shaft of the penis during palpation, bladder was not full. By digital rectal examination, the prostate was hard with indentation mostly representing palpable stones in the prostatic urethra and para prostatic diverticulum. Other extra genitourinary manifestations due to AKU disease were apparent; including the presence of thoracic lumbar back pain for the past 3 years with an incidental finding of advanced changes of AKU seen in the spine ( Fig. 1 A. KUB), short stature, and black discoloration of the nose and ear cartilages. Fig. 1 Supine KUB (A) showing numerous radiopaque stones at the projection of urinary bladder and prostate, note also advanced changes of alkaptonuria seen in spine, pre-operation non-contrast urinary tract CT (B + C) showing multiple stones in the urinary bladder and prostate. Fig. 1 Laboratory investigations revealed a normal complete blood count, kidney function tests, serum parathyroid hormone, uric acid, calcium, and prostate specific antigen (PSA). The only positive finding was the presence of red blood cells and white blood cells in his urine analysis; however, his urine culture results came back negative. A Kidney, Ureter and Bladder plain film (KUB) and unenhanced urinary tract computed tomography (CT) were done with results as shown in ( Fig. 1 A) and ( Fig. 1 B + C) respectively. Two operative sessions were done to completely clear his stones in the urethra, paraprostatic diverticulum and bladder. During the first operation, cystoscopy revealed multiple urethral, urinary bladder, and left para prostatic diverticulum black stones. His urethral stones were pushed back up to urinary bladder and cystolitholapaxy were used to eliminate urinary bladder stones. A 3-way urethral catheter was inserted into urinary bladder. Another unenhanced urinary tract CT ( Fig. 2 A + B) and pelvic magnetic resonance imaging (MRI) ( Fig. 2 C + D) were taken postoperatively. Fig. 2 Post operation non-contrast urinary tract CT (A + B) showing only few residual stones, the largest on the right side of the prostate and pelvic MRI coronal STIR (C) showing fluid filled diverticulum in the left lateral aspect of the prostate (arrow), axial T2 (D) showing the prostatic diverticulum containing tiny hypointense stone (arrow). Fig. 2 Few days after his first operation, the patient developed pulmonary embolism and started on an anticoagulant (enoxaparin), then the patient course was complicated by clot retention, so suprapubic catheter was inserted and patient was kept on continuous irrigation. Repeat cystoscopy revealed urethral and left paraprostatic diverticulum with multiple black stones that were then fragmented using a pneumatic lithotripter, and evacuated by inserting a 3-ways Foley’s catheter. An unenhanced urinary tract CT ( Fig. 3 ) was taken for comparison with the his baseline CT prior to operation ( Fig. 1 (B + C)). Fig. 3 Axial non-contrast urinary tract CT (A + B) show near completely removal of all stones (residual tiny stone in the prostate, arrow). Fig. 3 The weight of the stones was 78 g, and chemical calculus analysis showed black stones with a composition of 20% uric acids and 80% calcium oxalate. After few days from the last cystoscopy procedure, Foley’s catheter was removed followed by suprapubic catheter removal, after that, patient was passing urine with good stream and discharged home. The patient has been visiting outpatient clinic with a regular follow up visits without any bothersome urinary symptoms.'}", "questions": ["Describe the findings on the supine KUB and the pre‑operative non‑contrast urinary tract CT, including stone locations and any additional abnormalities such as spinal changes.", "Summarize the laboratory investigation results, detailing blood work, urine analysis (RBCs/WBCs), and urine culture outcomes.", "What did the post‑operative non‑contrast urinary tract CT and pelvic MRI (STIR and T2 sequences) reveal about residual stones and the characteristics of the prostatic diverticulum?", "What did the follow‑up axial non‑contrast urinary tract CT show regarding the extent of stone removal and any remaining stones?", "What were the findings of the chemical calculus analysis, specifying the composition percentages of uric acid and calcium oxalate in the stones?"], "ground_truth_arguments": ["Supine KUB ( A ) showing numerous radiopaque stones at the projection of urinary bladder and prostate, note also advanced changes of alkaptonuria seen in spine, pre - operation non - contrast urinary tract CT ( B + C ) showing multiple stones in the urinary bladder and prostate", "Laboratory investigations revealed a normal complete blood count, kidney function tests, serum parathyroid hormone, uric acid, calcium, and prostate specific antigen ( PSA ). The only positive finding was the presence of red blood cells and white blood cells in his urine analysis; however, his urine culture results came back negative", "Post operation non - contrast urinary tract CT ( A + B ) showing only few residual stones, the largest on the right side of the prostate and pelvic MRI coronal STIR ( C ) showing fluid filled diverticulum in the left lateral aspect of the prostate ( arrow ), axial T2 ( D ) showing the prostatic diverticulum containing tiny hypointense stone", "Axial non - contrast urinary tract CT ( A + B ) show near completely removal of all stones ( residual tiny stone in the prostate", "chemical calculus analysis showed black stones with a composition of 20 % uric acids and 80 % calcium oxalate"]}
{"id": "CaseReportBench:train-470", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What type of abdominal pathology was identified that prompted surgical intervention?", "What gastrointestinal symptoms were reported in the patient's presentation?"], "ground_truth_arguments": ["acute appendicitis", "nausea, and vomiting"]}
{"id": "CaseReportBench:train-249", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': \"A two-month-old female infant was transferred to Seoul National University Children's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg (<3rd percentile). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion. The initial laboratory findings after birth showed the following increased values on the liver function test: aspartate aminotransferase (AST), 176 U/L; alanine aminotransferase (ALT), 106 U/L; total bilirubin, 1.76 mg/dL; and direct bilirubin, 1.2 mg/dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non-diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract. The patient was fed with preterm formula milk without feeding intolerance. No definitive sepsis event occurred during her hospitalization. When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg/dL and a direct bilirubin level of 9.61 mg/dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum-ascites-albumin gradient level was elevated, and portal hypertension was suspected. By the age of 70 days, the infant was transferred to our hospital for further evaluation of persistent ascites suggesting portal hypertension and hyperbilirubinemia. On the day of admission to our unit, the infant's height was 42 cm (<3rd percentile), her weight was 2.9 kg (<3rd percentile), and her head circumference was 33.5 cm (<3rd percentile). A physical examination indicated whole-body jaundice, a markedly distended abdomen with ascites and an umbilical hernia. The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g/dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg/dL, a direct bilirubin level of 6.4 mg/dL, an AST level of 225 U/L and an ALT level of 114 U/L. The albumin level was 2.4 g/dL, and the ammonia level was increased to 149 µg/dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng/mL (normal values are 14.0-647.2 ng/mL), and the transferrin saturation was 97.2%. The serum alpha-fetoprotein level was in the high normal range (19,737.27 ng/mL; normal values are 40-19,953 ng/mL). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging (MRI) verified a diffuse heterogeneous low signal intensity in the liver on T2-weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra-hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non-diagnostic findings. The infant received supportive medical treatment, including fat-soluble vitamins, ursodeoxycholic acid, fresh frozen plasma, lactulose, diuretics, and sodium benzoate. Her general condition and coagulopathy were aggravated, and her vital signs were unstable. She was transferred to the intensive care unit on day 18 of hospitalization for further management. Her mother began the donor evaluation process. Active gastrointestinal bleeding was observed on day 21 of the infant's hospitalization, and an emergency living donor liver transplantation was performed. The infant was 3 months old, and her weight was 3 kg on the day of transplantation. The graft was tailored by reducing its left lateral section. The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining. The infant fully recovered from hepatic failure after liver transplantation. The infant was discharged one month after the operation. She exhibited normal renal function after transplantation. She received medical treatment for hyperkalemia, which occurred after the administration of tacrolimus. Following her discharge, the patient's neurological development was delayed, and she entered rehabilitation with outpatient clinic follow-up in the hospital's neurology department. Assessments by brain MRI and chromosomal study produced normal findings.\"}", "questions": ["What abnormalities were reported in the initial liver function tests and which infectious agents were investigated for neonatal hepatitis?", "What did the initial abdominal sonography reveal concerning the hepatobiliary tract and biliary atresia?", "At approximately 50 days of age, what changes in bilirubin levels, presence of ascites, coagulopathy, and serum‑ascites‑albumin gradient were described?", "Upon admission at around 70 days, what abnormalities were noted in the complete blood count and liver laboratory studies (including bilirubin, AST, ALT, albumin, ammonia, PT/INR)?", "What were the reported values and interpretation of serum ferritin, transferrin saturation, and alpha‑fetoprotein at that time?", "What did the metabolic evaluation reveal, including plasma amino acids and urine organic acids, and which metabolic disorder was excluded?", "What findings did the abdominal MRI show regarding liver signal characteristics on T2‑weighted images and their implication for iron deposition?", "What was the outcome of the oral mucosal biopsy performed to assess extra‑hepatic siderosis?", "Provide a concise summary of the histopathological findings described for the explanted liver, including iron deposition and any other notable features, as a single statement.", "What were the results of the post‑transplant brain MRI and chromosomal studies?"], "ground_truth_arguments": ["aspartate aminotransferase ( AST ), 176 U / L; alanine aminotransferase ( ALT ), 106 U / L; total bilirubin, 1.76 mg / dL; and direct bilirubin, 1.2 mg / dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non - diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract.", "When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg / dL and a direct bilirubin level of 9.61 mg / dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum - ascites - albumin gradient level was elevated,", "The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g / dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg / dL, a direct bilirubin level of 6.4 mg / dL, an AST level of 225 U / L and an ALT level of 114 U / L. The albumin level was 2.4 g / dL, and the ammonia level was increased to 149 µg / dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng / mL ( normal values are 14.0 - 647.2 ng / mL ), and the transferrin saturation was 97.2 %. The serum alpha - fetoprotein level was in the high normal range ( 19,737.27 ng / mL; normal values are 40 - 19,953 ng / mL ). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging ( MRI ) verified a diffuse heterogeneous low signal intensity in the liver on T2 - weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra - hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non - diagnostic findings.", "The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining.", "Assessments by brain MRI and chromosomal study produced normal findings. \""]}
{"id": "CaseReportBench:train-221", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case 2': \"The second case was of a 28-year-old male who was born of a non-consanguineous marriage, had delayed psychomotor milestones with mental retardation, congenital cataract, and recurrent episodes of diarrhea since early childhood. He had history of progressive spastic diplegia, tremulousness in both upper limbs and scanning speech. The patient had impaired attention, vigilance, comprehension, and new learning ability. Pan-sensory impairment was noted below knee with impaired limb coordination in upper limbs. Patient's skin biopsy of swelling over Achilles confirmed xanthoma. MRI brain showed altered signals in bilateral cerebral peduncles, ventral pons, both the middle cerebellar peduncles and medullary pyramids. Based on the clinical, radiological, and biopsy findings of the Achilles tendon swelling, diagnosis of CTX was confirmed.\", 'Case 1': 'A 50-year-old commerce graduate with degree in law presented to us with insidious onset gradually progressive spastic diplegia for 20 years followed later by gradually progressive bladder dysfunction, poor scholastic performance, and a single seizure. He was born to non-consanguineous parents and had unremarkable early psychomotor development. Pedigree analysis revealed absence of any family history in previous two generations. On examination, patient had thoracic kyphosis with contractures at hip, knee, and ankle joints. He had firm, non-tender swellings over ankles, patella, and elbows bilaterally. Detailed higher mental function assessment revealed impairment of attention, new learning and visual memory with normal language functions. His speech was slow and slurred but could be comprehended with little difficulty. All cranial nerve functions were intact. The patient had severe spasticity in both lower limbs with brisk deep tendon reflexes in both the upper and the lower limbs, extensor plantar responses, and normal sensory examination. Blood investigations revealed a normal complete hemogram (including hemoglobin, total leukocyte count, differential leukocyte count), liver and kidney function tests, serum electrolytes and, triglyceride and cholesterol levels. X-rays of ankle, knee, and elbow showed homogenous soft tissue swelling. MRI brain showed T2-weighted hyperintensities in dentate nucleus regions bilaterally and generalized cerebral and cerebellar atrophy. Plasma cholestanol levels were found to be raised suggesting cerebrotendinous xanthomatosis. The genetic analysis of CYP27A1 gene of the patient was carried out by the method of Polymerase Chain Reaction and sequencing of both the DNA strands was done. The analysis revealed heterozygous mutation in exon 6 with substitution of cytosine by thymine at 1151 position (c. 1151C > Tp.P384L) and a novel mutation in exon 1 of CYP 27 gene with substitution of thymine by cytosine at nucleotide position 2 of the gene (c. 2T > Cp.M1T). The mutation in exon 6 is already described as disease causing while the mutation in exon 1 is previously unreported as per the current Human Gene Mutation Database. The mutation causes loss of a highly conserved start codon and likely results in loss of functional protein. The patient is receiving atorvastatin besides physical therapy and chenodeoxycholic acid (CDCA) is being arranged as it is not marketed in India.'}", "questions": ["What diagnostic procedure was performed on the swelling over the Achilles tendon?", "What observations were documented regarding the swellings over the ankles, patellae, and elbows?", "What imaging study was obtained to evaluate the soft‑tissue swellings at the ankle, knee, and elbow?"], "ground_truth_arguments": ["skin biopsy of swelling over Achilles confirmed xanthoma.", "firm, non - tender swellings over ankles, patella, and elbows bilaterally", "homogenous soft tissue swelling."]}
{"id": "CaseReportBench:train-84", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What are the patient's demographic details (age, marital status, gender, place of residence) and overall physical and mental development, along with the early symptoms she experienced?", "Can you describe the patient's dental eruption and loss pattern, and the sequence in which skin changes first appeared on her feet and later on her hands?", "What skin condition affecting the palms and soles is reported in the patient’s parents, and how is it characterized?", "What does the patient report about similar palmar‑plantar hyperkeratosis among her neighbors, and do those neighbors have any other associated health complaints?", "In what ways are the palmo‑plantar hyperkeratotic lesions observed in the patient similar to those seen in her parents and the affected neighbors?"], "ground_truth_arguments": ["A 20 - year - old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall - out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva ( xerostomia ), poor formation of tear ( xerophthalmia ), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood.", "The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable.", "There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar - plantar hyperkeratosis without any other complaints she presented, particularly dental problems.", "similar palmo - plantar hyperkeratotic lesions of her parents and of few neighbors"]}
{"id": "CaseReportBench:train-224", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'Case 5': 'A 62-year-old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5-year history of an asymptomatic eruption on the neck. Physical examination revealed numerous soft, oval-to-round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area. Echocardiography was unremarkable. The ophthalmologic examination was normal. Moreover, no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption.', 'Histopathology of cases (1–3)': 'A skin punch biopsy was performed, and the hematoxylin and eosin (H and E) sections revealed a normal-appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.', 'Histopathology of case 4 and 5': 'H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident.', 'Case 3': \"A 68-year-old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years. Physical examination revealed numerous tan to yellowish soft papules over the lateral side of the patient's neck, measuring 2–3 mm. The patient had no systemic symptoms and was otherwise healthy.\", 'Case 4': \"A 61-year-old female patient presented to the clinic with a 2-year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis. On physical examination, there were multiple symmetrically distributed, skin-colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient's neck, upper chest, and the antecubital fossa of both forearms. There was no history of sun exposure or family history of similar cutaneous manifestation.\", 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Case 2': \"A 77-year-old female presented with a 4-year history of gradual appearance of small skin-colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension. However, other systemic examinations were unremarkable, especially for eye, cardiac, or gastrointestinal systems.\", 'Case 1': 'A 71-year-old female presented with a 1–2-year history of asymptomatic skin-colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints. Given the clinical resemblance to PXE, an ophthalmology consult was performed to rule out the presence of angioid streaks. The eye examination was normal.'}", "questions": ["What chronic respiratory conditions are documented for the patient?"], "ground_truth_arguments": ["chronic obstructive pulmonary disease", "asthma"]}
{"id": "CaseReportBench:train-532", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case 2': 'Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady. At the dermatological examination grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region ( Figure 4 ). The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers, confirming the diagnosis of pseudoxanthoma elasticum ( Figure 5 ). Right ophthalmoscopy, retinography and angiography revealed angioid streaks ( Figure 6 ). Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal.', 'Case 1': 'Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family. At the dermatological examination, coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae ( Figure 1 ) were observed. The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis, compatible with the diagnosis of pseudoxanthoma elasticum ( Figure 2 ). Cardiological evaluation did not show changes (normal electrocardiogram and echocardiogram). Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography ( Figure 3 ).'}", "questions": ["What life stage (e.g., infancy, childhood, adolescence, adulthood) is reported for the initial appearance of the skin lesions?"], "ground_truth_arguments": ["The lesions started during infancy"]}
{"id": "CaseReportBench:train-60", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory. Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE. Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium. The patient is being followed up and has been specifically instructed to report if she becomes pregnant.'}", "questions": ["What clinical diagnosis was established for the patient based on the skin lesions and histology?", "Which specific disorder does the case report identify as the cause of the described dermatologic findings?", "What condition is referred to by the abbreviation used in the case report?"], "ground_truth_arguments": ["PXE"]}
{"id": "CaseReportBench:train-487", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What laboratory abnormalities were reported, including inflammatory markers, blood counts, serum protein electrophoresis, and the results of investigations for fever, thyroid function, glucose levels, and auto‑antibody testing?", "What combined histopathological and immunohistochemical findings were described in the skin biopsy report?", "Which imaging studies were performed and what overall abnormalities were identified across them (e.g., abdominal ultrasound, chest radiography, echocardiography)?"], "ground_truth_arguments": ["ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g / dl, and a platelet count of 5.14 lakhs / cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post - prandial blood sugar levels were normal. Anti - nuclear antibodies ’ titer was negative", "Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate", "An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein"]}
{"id": "CaseReportBench:train-68", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'This boy was born to nonconsanguineous Chinese parents. He was born at term, weighed 3100 g with good Apgar scores. He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia. He was brachycephalic with hypopigmented hair. He had poor weight gain with swallowing dysfunction and significant reflux disease requiring gastrostomy feeding. He started having orofacial and limb dyskinesias at 1.5 years of age and subsequently developed refractory multifocal epilepsy at 3 years of age requiring multiple antiepileptics and ketogenic diet to control his seizures. Electroencephalogram showed focal and diffuse slowing consistent with background encephalopathic state, with frequent multifocal epileptiform discharges bilaterally. He developed central and obstructive sleep apneas at 3.5 years of age and was initiated on night bilevel positive airway pressure. He was evaluated with magnetic resonance imaging brain scan and chromosomal microarray at 8 months of age, which was normal. Whole-exome sequencing and direct sequencing confirmed that he harbored compound heterozygous missense mutations c.3130C>T (p.Arg1044Cys), c.3430C>T (p.Arg1144Cys), and c.4078G>A (p.Ala1360Thr) in the LRPPRC gene mapped to chromosome 2p21-p16. Parents were carriers of the mutation. His muscle biopsy showed normal muscle architecture with no “ragged-red” fibers, necrotic fibers, or regenerating fibers seen. Cytochrome c-oxidase was positive in most of the fibers. There were no light microscopic or ultrastructural features to support mitochondrial myopathy. Respiratory chain enzymes in skeletal muscle were diagnostic for complex IV defect ( Table 1 ). He is currently 5 years of age, has generalized dystonia, and is mainly chair-bound. He has intermittent eye contact and minimal vocalization. His baseline lactates ranged from 1.5 to 3.6 mmol/L with mild intermittent metabolic acidosis. However, there were no episodes of acute ketosis, glycemic derangements, or any acute stroke-like episodes. The parents’ first child was diagnosed with steroid-resistant nephrotic syndrome at 18 months of age requiring tacrolimus treatment. Their second pregnancy was terminated at 22 weeks’ gestation due to antenatal diagnosis of Ebstein’s anomaly and multiple valvular abnormalities.'}", "questions": ["At what age was the patient's global developmental delay first identified?"], "ground_truth_arguments": ["7 months of age"]}
{"id": "CaseReportBench:train-602", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Presentation': 'A 22-year-old Hispanic female with a past medical history of dysmenorrhea and recurrent urinary tract infections (UTIs), previously diagnosed by her primary care physician, presented with an 8-day history of no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation. She had tried multiple laxatives for symptom relief. She also reported frequent antibiotic usage, most recently ciprofloxacin, for recurrent UTIs. She had previously been prescribed an oral contraceptive for dysmenorrhea, but it was recently discontinued due to severe nausea and negligible improvement of her abdominal pain. On presentation, she was afebrile (36.7°C), had a normal heart rate (85 beats per minute), normal respiratory rate (16 breaths per minute), and was normotensive (121/80 mmHg). On physical examination, the patient was alert and oriented to time, place, and person without any objective signs of anxiety, depression, psychosis, or other appreciable psychiatric disturbances. The abdomen was soft, nondistended, with mild upper abdominal and periumbilical tenderness. Laboratory examinations were remarkable only for hyponatremia of 130 mEq/L and hypoalbuminemia at 3.4 g/dL. Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm/kg and urine sodium was 100 mEq/L, indicating a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Her initial computerized tomography (CT) scan of the abdomen and pelvis ( Figure 1 ) revealed a diffusely dilated small bowel filled with fecal matter and marked colonic distention with cecal dilatation measuring 9 cm. She was kept nil per os, except for medications, and a nasogastric tube was placed for bowel decompression. A colonoscopy found only granular and punctate erythematous mucosa in the rectum and sigmoid colon with mild nonspecific ileitis and successfully decompressed the dilated colon. A few days after decompression, she developed several watery bowel movements and continued to have abdominal pain. Rapid stool studies were obtained and returned positive for Clostridium difficile antigen and toxin A&B. She was treated with oral vancomycin for 10 days. A repeat CT scan of her abdomen ( Figure 2 ) noted no further small bowel dilation, free air, or free fluid. CT enterography showed no bowel wall thickening or imaging features to suggest inflammatory bowel disease. Her appetite improved, but her abdominal pain persisted despite the antibiotic course, and pain remained out of proportion to her physical examination. The differential was broadened to include AIP. A random urine PBG was elevated at 99.9 mg/g (normal < 0.22 mg/g), with a urine delta aminolevulinic acid (ALA) elevated at 71.9 mg/g (normal < 5.4 mg/g). The fractionation of porphyrins in plasma ( Table 1 ) and urine ( Table 2 ) was suggestive of a biochemical diagnosis of AIP. Intravenous (IV) hematin 1 mg/kg/d and IV dextrose were given for 3 days. After hematin/dextrose therapy, her abdominal pain and bowel symptoms resolved. On subsequent questioning, it was found that she had no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures within our medical institution. She improved clinically and was later discharged with education on how to reduce AIP acute attacks and followed as an outpatient by hematology. Two weeks after discharge, the patient was seen by her primary care physician and noted significant improvements in her appetite and abdominal pain without recurrence of constipation or diarrhea.'}", "questions": ["Describe the patient's bowel movements and the quality of her abdominal pain at the time of presentation.", "What gastrointestinal symptoms, including nausea, did the patient experience after stopping oral contraceptives, and how did they affect her abdominal pain?", "What were the findings on abdominal physical examination regarding tone, distention, and tenderness location?", "How did the patient's appetite and abdominal pain change following the administered treatments?", "In what way did the intensity of the patient's pain compare to the objective findings on physical examination?", "What was the status of the patient's abdominal pain and bowel symptoms after completion of hematin and dextrose therapy?"], "ground_truth_arguments": ["no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation", "severe nausea and negligible improvement of her abdominal pain", "The abdomen was soft, nondistended, with mild upper abdominal and periumbilical tenderness", "Her appetite improved, but her abdominal pain persisted", "pain remained out of proportion to her physical examination", "abdominal pain and bowel symptoms resolved"]}
{"id": "CaseReportBench:train-308", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case presentation': 'A 10-day-old male infant presented to the emergency department with a 3-day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg (2nd–9th centile); length 49.0 cm (25th centile) and head circumference 36.0 cm (9th–25th centile). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents (first cousins) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family. On initial examination, he was crying, alert, but bradycardic (heart rate of 65 beats/min), with sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle. His respiratory rate was 50 breaths/ min and was saturating at 99% in air. His preductal oxygen saturation was 98% in air and postductal oxygen saturation was 97% in air. His chest was clear and he had a 2/6 systolic murmur best heard in the pulmonary area. Examinations of the respiratory system and abdomen were within normal limits. His ECG showed broad complex bradycardia. His blood pressure was recorded as 92/56 mm Hg (above 50th centile). His initial blood gas showed the following: pH 7.30 (7.35–7.45), HCO 3 16.1 mmol/L (22–28 mmol/L), BE −9.0 mmol/L (−4.0 to +4.0 mmol/L), Na 112 mmol/L (135–145 mmol/L), K 9.7 mmol/L (3.5–5.0 mmol/L), ionised Ca 1.16 mmol/L (1.0–1.3 mmol/L), glucose 3.9 mmol/L (3.0–6.5 mmol/L) and lactate of 3.3 mmol/L (<2 mmol/L). Treatment with intravenous cefotaxime (25 mg/kg) and intravenous amoxicillin (30 mg/kg) was commenced for suspected sepsis. However, the hyponatraemia and hyperkalaemia were out of proportion to his clinical condition. Following the results of the blood gas, his genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant’s skin tone. A probable diagnosis of CAH with salt-wasting crisis with arrhythmia was made and treatment was commenced. He was given high flow oxygen via non-rebreathing mask; 20 mL/kg of 0.9% saline bolus; continuous nebulised salbutamol (2.5 mg); stat dose of calcium gluconate intravenously (0.11 mmol/kg); hydrocortisone intravenously (4 mg/kg) and fludrocortisone acetate (50 mcg). Sodium bicarbonate infusion (1 mmol/kg) was also commenced. Following the administration of the above interventions, his heart rate rose to 150 beats/min. His repeat ECG showed regular sinus rhythm within a period of 40 min of arrival to the emergency department. An echocardiogram was done, and it was normal. A diagnosis of CAH secondary to 21-hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies. His glucose and electrolytes have been monitored daily while in the hospital, and they gradually improved to satisfactory levels. He was discharged home with oral hydrocortisone (2 mg/kg 6 hourly), fludrocortisone acetate (50 mcg once daily) and 0.9% sodium chloride (1 mmol/kg twice daily). An instruction to his parents was given to double the dose of his oral hydrocortisone if the baby has intercurrent illness (eg, fever, cough, vomiting and diarrhoea). They were also given an emergency card/passport so that he can be assessed and managed immediately by the paediatric team whenever he presents to the hospital.'}", "questions": ["What were the infant's arterial blood gas results, including pH, bicarbonate (HCO₃⁻), base excess, sodium, potassium, ionized calcium, glucose, and lactate values?", "What were the findings of the echocardiogram performed on the infant?", "Which specific genetic mutation was identified by genetic studies in this patient?"], "ground_truth_arguments": ["His initial blood gas showed the following : pH 7.30 ( 7.35–7.45 ), HCO 3 16.1 mmol / L ( 22–28 mmol / L ), BE −9.0 mmol / L ( −4.0 to +4.0 mmol / L ), Na 112 mmol / L ( 135–145 mmol / L ), K 9.7 mmol / L ( 3.5–5.0 mmol / L ), ionised Ca 1.16 mmol / L ( 1.0–1.3 mmol / L ), glucose 3.9 mmol / L ( 3.0–6.5 mmol / L ) and lactate of 3.3 mmol / L ( < 2 mmol / L )", "An echocardiogram was done, and it was normal", "mutation in CYP21A2 was confirmed by genetic studies"]}
{"id": "CaseReportBench:train-590", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["What was the age of each patient at the time they presented for treatment?"], "ground_truth_arguments": ["65 years old"]}
{"id": "CaseReportBench:train-575", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case 2': 'An 18-year-old girl was admitted to our hospital following development of generalized tonic-clonic seizure in November 2016. Ten days ago, she was diagnosed with ileus because of abdominal pain as well as constipation in her local hospital. However, the symptoms were not relieved and a series of tests including abdominal X-ray, CT scan, and ultrasound were normal. Her brain MRI was performed in her local hospital indicating PRES (Fig. 3 ). MR angiography showed no abnormality (data not shown). However, the diagnosis was vague and the patient was transferred to the emergency department of our hospital due to seizures. Anticonvulsants including benzodiazepines and oxcarbazepine were used to control the seizures. The recurrent abdominal pain and seizures gave us reason to suspect of AIP, given the prognosis from case 1. She had no family history of similar symptomatology or other particularly notable medical history. At the time of admission, her blood pressure was 136/101 mm Hg, and her heart rate was 109/min. The general physical examination was normal and there was no focal neurological deficit. On the night of admission, the patient had hallucination. Except for remarkable hyponatremia of 104 mmol/L, her serum potassium was 3.0 mmol/L, aspartate transaminase 243 U/L, alanine transaminase 142 U/L, and total bilirubin 37 μmol/L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero-negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid (CSF) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution (Fig. 4 ). AIP was confirmed by 3 repeated urine Watson–Schwartz tests. The patient was given a high carbohydrate diet and intravenous dextrose. No hematin was available for her, but her status improved gradually when she was discharged. No seizures occurred, and her abdominal pain regressed. Two weeks later, a repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions (Fig. 5 ). One month later, she recovered completely and went back to work. No acute attacks have occurred to date. Because this was cases report without any research involving human beings or experimental subjects, the ethical approval was not required in our institute. But patients have provided informed consent for publication of the case.', 'Case presentation:': \"Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson–Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up.\", 'Case 1': 'In December 2014, a 27-year-old man was admitted to our hospital for abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week. He was diagnosed with acute pancreatitis with mild elevated urine amylase in his local hospital. No abnormalities were found in his abdominal computed tomography (CT) and X-ray. However, the paroxysmal pain was not relieved, and his blood pressure increased. Six days later, a generalized tonic-clonic seizure occurred. Then, partial seizures in the left limb continued. He was transferred to our hospital. No particular medical or family history was reported. At the time of admission, he described recurrent severe paroxysmal abdominal and lumbar pain. His clinical examination was unremarkable, except for decreased tendon reflex in the 4 limbs. There was no complaint of visual disturbance. The patient had moderately increased blood pressure (159/101 mm Hg) and tachycardia (112/min). His creatine kinase was 246 U/L (normal, 0–170 U/L), aspartate transaminase was 42 U/L (15–40 U/L) and serum sodium was 130 mmol/L (normal, 137–147 mmol/L). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1-weighted images and were hyperintense on T2-weighted and fluid-attenuated inversion recovery images. Diffusion-weighted images (DWI) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient (ADC) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES (Fig. 1 ). There was mild contrast enhancement (data not shown). Electroencephalography showed diffuse slow waves without epileptiform discharges. The results of the cerebrospinal fluid analysis were normal. His severe recurrent abdominal pain without clear etiology was suspect of AIP. The diagnosis of AIP was made after 3 repeated positive urine Watson–Schwartz tests for porphobilinogen (PBG). His urine turned dark and red upon exposure to light (Fig. 2 ). Glucose infusion and a high carbohydrate diet were given to the patient, as hematin was not available in our hospital. The patient responded well and recovered gradually. He was discharged with no seizure or abdominal pain. Upon review, he remained asymptomatic.'}", "questions": ["What were the patients' blood pressure and heart rate measurements, and were any abnormalities such as hypertension or tachycardia noted?"], "ground_truth_arguments": ["blood pressure increased", "moderately increased blood pressure ( 159/101 mm Hg ) and tachycardia ( 112 / min )"]}
{"id": "CaseReportBench:train-549", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case 2': 'Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady. At the dermatological examination grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region ( Figure 4 ). The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers, confirming the diagnosis of pseudoxanthoma elasticum ( Figure 5 ). Right ophthalmoscopy, retinography and angiography revealed angioid streaks ( Figure 6 ). Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal.', 'Case 1': 'Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family. At the dermatological examination, coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae ( Figure 1 ) were observed. The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis, compatible with the diagnosis of pseudoxanthoma elasticum ( Figure 2 ). Cardiological evaluation did not show changes (normal electrocardiogram and echocardiogram). Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography ( Figure 3 ).'}", "questions": ["Describe the color, size (e.g., micropapules), symptomatology, and initial location of the papular skin lesions reported in each case.", "Detail the subsequent progression and anatomical distribution of the papules, including any formation of plaques, grouping, or symmetry across regions such as the cervical area, axillae, cubital fossae, popliteal fossa, inguinal and periumbilical zones.", "What histopathological abnormalities were identified in the skin biopsies, and which dermal layers were involved?"], "ground_truth_arguments": ["yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas.", "grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region", "The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers", "yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae.", "coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae", "The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis,"]}
{"id": "CaseReportBench:train-397", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["What was the patient's age at the time of presentation (in years)?"], "ground_truth_arguments": ["17 - year - old"]}
{"id": "CaseReportBench:train-313", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'XY2 is a boy of seven years of age with X-linked hypophosphatemia. He inherited this genetic disorder from his mother, who in turn inherited it from her father. Mutations in the PHEX gene to Xp22.1 are responsible for the clinical impression of X-linked hypophosphatemia. A molecular analysis of the PHEX gene and sequence analysis showed a hemizygote 1735 G>A(G579R) missense mutation in exon 17 of the PHEX gene in all subjects. XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth. XY2 is intellectually gifted (WISC-III Full Scale IQ: 135, Verbal IQ: 136, Performance IQ: 133) Psychiatric examination demonstrated a DSM-IV-diagnosis of AD, confirmed by the ADI-R (autism diagnostic interview - revised) of the parents and the ADOS-G (autism diagnostic observation schedule). XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X-linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI-R was conducted with the parents and an ADOS-G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC-III test. XY1 is of normal intelligence (total IQ: 107, verbal IQ: 106, performance IQ: 107). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism'}", "questions": ["What basic demographic information and genetic diagnosis are reported for XY2?", "From which family members was the X‑linked hypophosphatemia in XY2 reported to have been transmitted?", "What developmental concerns prompted XY2's parents to seek evaluation, and what academic and social observations did they note?", "What growth limitation is attributed to XY2's hypophosphatemia?", "How is XY2 positioned among his siblings, and what is known about the presence of X‑linked hypophosphatemia in his brothers?", "What types of psychiatric assessments were conducted for XY1 regarding autism, and how were the results described relative to diagnostic criteria?", "What cognitive domains were evaluated for XY1 using the WISC‑III, and how was his overall intellectual performance characterized?", "What does the family history reveal about autism spectrum traits, including the autism‑quotient scores of parents, grandparents, and siblings, and any notable findings?"], "ground_truth_arguments": ["XY2 is a boy of seven years of age with X - linked hypophosphatemia", "He inherited this genetic disorder from his mother, who in turn inherited it from her father", "XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth.", "XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X - linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI - R was conducted with the parents and an ADOS - G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC - III test. XY1 is of normal intelligence ( total IQ : 107, verbal IQ : 106, performance IQ : 107 ). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism '"]}
{"id": "CaseReportBench:train-265", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case': \"A 27-year-old female was admitted to the hospital because of left hemiplegia and aphasia. She was 162 centimeters tall and 30 kilograms in weight. She was born after a normal pregnancy and delivery. There was no family history of neurological diseases. Motor and intellectual development was normally attained during infancy. She was hospitalized for general muscle weakness and gait disturbance when she was 6 years old. A neurologic exam showed decreased muscle tone and strength, and atrophic muscle mass. She had consistent muscle weakness, so a muscle biopsy was performed from the calf muscle when she was 8 years old. The biopsy showed mitochondrial myopathy of the pleoconial type. Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems. Follow-up procedures were performed in an outpatient clinic once or twice a year. When she was 24 years old she had sudden syncope. An magnetic resonance imaging (MRI) revealed acute infarction of the left basal ganglia and the left frontal lobe. Two years later, when the patient was 26, she had another stroke and presented with general weakness, aphagia, and dysarthria. An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia. These clinical and radiological findings suggested brain involvement of MELAS syndrome. Thus, further evaluation was done for MELAS syndrome including blood lactate and genetic analysis. The plasma lactate level was 21.8 mg/dL (normal range 4.5-19.8 mg/dL). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng/dL (normal range 0.89-1.76 ng/dL) and TSH was 0.04 µIU/mL. Levels of complement component 3 and 4 were 13 mg/dL (normal range 75-145 mg/dL) and 18 mg/dL (normal range 12-72 mg/dL) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti-double stranded DNA was 1.6 (normal range 0-6). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation: m.3303C>T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome. She was treated with supportive care and rehabilitation for a month and was then discharged. Warfarin was used during the hospital stay, but was stopped when she was discharged, because MELAS syndrome causes nonvascular infarct and there is no report about the related risk of thromboembolism. One year later, she presented with another stroke with associated left sided weakness, and was subsequently admitted to the hospital. Her vital signs were stable and there were no specific findings in chest X-rays or electrocardiography. Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25%. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 ). The patient's mental status and general condition improved after she was treated with mannitol and anticoagulation therapy. Rehabilitation and supportive care, including warfarin, were followed and maintained. The patient was discharged after a month.\"}", "questions": ["Which category of metabolic disorder is suggested by the clinical, radiological, and genetic findings?"], "ground_truth_arguments": ["MELAS syndrome"]}
{"id": "CaseReportBench:train-94", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case report': \"A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission.\"}", "questions": ["What limb-related malformation category was identified in the patient?", "What limb abnormalities were observed in the patient?", "What were the findings of the spine ultrasound?"], "ground_truth_arguments": ["postaxial polydactyly of the left foot", "Spine ultrasound revealed no vertebral anomalies", "limb abnormalities", "postaxial polydactyly of the left foot"]}
{"id": "CaseReportBench:train-553", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Observation': 'An 18-month-old boy born after an uncomplicated full-term pregnancy was hospitalized for psychomotor regression and drug-resistant myoclonic epilepsy. There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected. The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay. Physical examination revealed a macrocephaly of 51 cm with a dysmorphic syndrome consisting of a frontal bossing and a broadening of the nasal bridge. The neurological examination revealed an axial hypotonia with no further optical problems or responsiveness to light. Ophthalmologic examination showed a cherry-red spot without optic atrophy. Cerebral computed tomography (CT) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter (Fig. 1 ). With magnetic resonance imaging (MRI) the thalamus was hyperintense on T1-weighted images and hypointense on T2-weighted images (Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem. Clinical data and thalamic involvement suggest metabolic diseases such GM2 gangliosidosis (e.g. Tay-Sachs and Sandhoff diseases) or GM1 gangliosidosis (e.g. Landing disease), Canavan disease or Alexander disease. Chromatography of amino acids in the blood, urine and cerebrospinal fluid (CSF) was normal and chromatography of organic acids in the urine was also normal. Enzymatic assays were performed in France and revealed a deficiency of both hexosaminidases A and B confirming the diagnosis of Sandhoff disease.'}", "questions": ["What was the patient's age at the time of presentation or hospitalization?"], "ground_truth_arguments": ["18 - month - old"]}
{"id": "CaseReportBench:train-120", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'CASE REPORT': 'A 4-year-old female patient with a nasal anomaly was admitted to our outpatient clinic. She was born 2300 g prematurely on her 37 th gestational week from a 34-year-old mother with a history of five pregnancies, two still births and two abortions. On her physical examination, she had a left-sided supernumerary nostril and cliteromegaly. Her laboratory studies revealed low levels of androstenedione and her history showed that she had medical therapy for 1 year for her congenital adrenal hyperplasia. No additional anomaly except patent foramen ovale was detected in her work-ups. Paranasal sinus computed tomography study revealed that her left-sided accessory nostril opened to the left nasal cavity. The patient was operated, the opening of the supernumerary nostril to the nasal cavity was obliterated and the widened nostril was narrowed by excisions from the alar ground and lateral side. A revision toward the nostril asymmetry is planned 1 year after the operation.'}", "questions": ["What cardiac anomaly was identified in the patient?"], "ground_truth_arguments": ["patent foramen ovale"]}
{"id": "CaseReportBench:train-521", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["Did the patient have elevated systolic blood pressure consistent with hypertension during the hospital stay?"], "ground_truth_arguments": ["significant hypertension ( systolic blood pressure 180 mm Hg )"]}
{"id": "CaseReportBench:train-231", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'A 38-year-old female presented to the out-patient department with a 6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week. The patient gave no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits. On cutaneous examination, prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin-colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin-colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face. Fundus examination of both eyes showed dark brownish-red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks. 2D-echo and electrocardiogram were investigated to check for cardiac involvement but were normal. A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid-dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material (mucin). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition. Based on the clinical and histopathological findings, a diagnosis of PXE was made. The patient was started on oral and topical sunscreens, advised rigid eye protection to prevent accidental blunt trauma, and regular follow-up.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Provide a single combined description of the duration and anatomical sites of the patient's skin laxity.", "Describe the cutaneous findings, specifying skin folds, wrinkles, and any papules (including size, color, and location).", "Summarize the histopathological findings from the neck skin biopsy, covering epidermal appearance, collagen changes, sclerotic areas, mucin presence, elastic‑fiber morphology, and calcium deposition."], "ground_truth_arguments": ["6 year history of increased laxity of the skin over the neck, thighs, and abdomen", "prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin - colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin - colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face", "A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid - dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material ( mucin ). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition"]}
{"id": "CaseReportBench:train-295", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}", "questions": ["What is the patient’s age and gender?", "What is the specific diagnosis of the patient’s congenital adrenal hyperplasia, including its classification and enzyme deficiency?", "What fertility‑related symptom did the patient present with?", "What testicular condition was documented in the patient, and was it bilateral?"], "ground_truth_arguments": ["A 28 - year - old man with classic salt - wasting CAH due to 21 - hydroxylase deficiency presented with subfertility. He had known bilateral TARTs"]}
{"id": "CaseReportBench:train-184", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Report': 'A 29-year-old male patient presented with a 6-year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk. He complained of skin tightness around the abdomen while walking. He wandered to and fro between different specialists but without much help. He was diagnosed as Type 1 diabetic 6 years back and was receiving insulin since then. Cutaneous examination revealed large ill-defined hyperpigmented indurated plaques extending symmetrically from mid-truncal area to both thighs characteristically sparing the knees and medial aspect of buttocks. A prominent constriction band was noted around the abdomen. The lesions over thighs were associated with hypertrichosis and were warm to touch. Examination also revealed short stature (145 cm), hypospadias, micropenis, scrotal swelling, and mild hepatomegaly and inguinal lymphadenopathy. Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal. Nails and teeth were normal. Ophthalmologic and auditory examinations were normal. On the basis of cutaneous findings, we kept differential diagnosis of morphea profunda, pseudoscleroderma, POEMS syndrome, Rosai–Dorfman syndrome, pigmented hypertrichotic dermatosis, and scleredema as the possibilities. A deep skin biopsy was done from the indurated plaque on the lateral part of the left thigh and sent for histopathology. Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes. Routine laboratory investigations revealed a fasting blood glucose level of 250 mg/dL and random blood sugar of 338 mg/dL with glycated hemoglobin 10.2%. Thyroid profile, liver function, kidney function, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibody was negative. Ultrasound abdomen revealed mild hepatosplenomegaly and abdominal lymphadenopathy. Color Doppler study of the scrotal region revealed small penis, normal echotexture, no calcific plaques, and small left testis. Chest radiography and nerve conduction studies were normal. Computed tomography (CT) demonstrated marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees. Para-aortic and inguinal lymphadenopathy and mild pericardial effusion were noted. Marked thickening of the scrotum was seen. A diagnosis of “H syndrome” was made. Genetic testing was not possible due to resource constraints.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.'}", "questions": ["What definitive diagnosis or syndrome was assigned to the patient in this case report?", "Which specific disorder does the report identify as the cause of the cutaneous sclerosis and systemic findings?", "Based on the clinical, histopathological, and imaging results, what named syndrome was concluded?", "What is the final diagnostic label (syndrome) mentioned by the authors for this patient?"], "ground_truth_arguments": ["H syndrome"]}
{"id": "CaseReportBench:train-579", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case': \"A 36 years man presented with severe obstructive LUTS. On digital rectal examination prostate was hard and nodular. Flow was a Q max of 2 mL/s for a voided volume of 130 mL and post void residual urine volume of 380 mL. Prostate specific antigen (PSA) was 0.393 ng/mL, while X-ray of pelvis showed punctate calcification in the region of pubic symphysis ( Fig. 1 ), computerized tomography scan of pelvis showed extensive and well calcified areas into the prostatic parenchyma ( Fig. 2 ). On further evaluation, he gave history of passage of dark colored urine and chronic low back ache. He was short statured with kyphotic spine. Osler's sign (bluish discolouration of sclera) was present ( Fig. 3 ). Biochemical analysis of urine showed the presence of homogentisic acid. These findings confirmed the diagnosis of alkaptonuria. He underwent transurethtral clearance of prostatic calculi which revealed multiple blackish calculi in prostatic urethra and in prostatic fossa ( Fig. 4 ) and clearance of calculi. On biochemical analysis, calculi were composed of calcium oxalate and uric acid. Figure 1 Punctate calcification in the region of pubic symphysis by X-ray of pelvis. Figure 2 Extensive prostatic calcification by computerized tomography. Figure 3 Osler's sign. Figure 4 Cystoscopic view of prostatic urethra contaning calculi and postprocedure extracted calculi.\"}", "questions": ["What eponymous ocular sign is mentioned in the case?", "What ocular sign was observed in the patient?"], "ground_truth_arguments": ["Osler 's sign ( bluish discolouration of sclera ) was present", "Osler 's sign"]}
{"id": "CaseReportBench:train-454", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case Report': 'Our case was a 1-year 5-month-old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath-holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium. The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby’s parents were consanguineous cousins. The father’s thalassemia status could not be elicited. On examination, the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm and the baby was conscious and alert. There was no jaundice or dehydration or abnormal odor. Arterial oxygen saturation (SpO 2 ) was 94%. The capillary refill time was between 3 s and 4 s. The heart rate was 146/min. The respiratory rate was 26/min. Non-invasive blood pressure was 73/44 (54) mm Hg. Respiratory system examination revealed normal chest movements with equal air entry on both sides. Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt. Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs. Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal. The eyes, musculoskeletal system, skin, and cardiovascular systems were normal. The baby was admitted for observation and investigations, and the initial differential diagnosis included alkaptonuria, myoglobinuria, hemoglobinuria, porphyria, and hemochromatosis. He had an under-current viral illness, which was managed symptomatically. The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g/dl (normal 10.5-14 g/dl), packed cell volume, mean corpuscular volume (MCV) and mean corpuscular hemoglobin were low at 31.9% (normal 32-42%), 68 fl (normal 72-88 fl), and 21.8 pg (normal 24-30 pg), respectively. MCV concentration was 32% (normal 31.5-34.5%) and red cell distribution width 17.1% (normal 11-16%). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high-pressure liquid chromatography (HPLC) revealed Hb A0 to be 80.4% and Hb A2 to be 6.1% (normal 2.40-3.60). The HPLC picture on correlation with the complete hemogram suggested β-thalassemia trait. DNA studies confirmed the beta globin gene defect of β-thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ-amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine. No abnormalities were detected on the electroencephalogram, leading us to believe that the breath holding spells were due to anemia. Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict’s reagent, strong alkali (filter paper impregnated with 10% sodium hydroxide turned black within 5 min when dipped into the urine) and ferric chloride (addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color). The urine of an alkaptonuric individual usually appears normal when passed. However, it starts to darken upon standing, and this is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Benedict’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test (with multistix) was negative excluding the role of glucose as reducing substance. For the qualitative assay of HA, to 0.5 ml of sample, a few drops of 10% ammonia was added followed by the addition of 3% silver nitrate solution. A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg/dl (normally HA is not present in urine). Parents’ urine was negative for HA. Due to the financial constraints, confirmatory diagnosis by DNA mutation analysis could not be carried out. The child was treated symptomatically, and he was given vitamin C (50 mg once a day for 3 months), low phenylalanine and tyrosine diet, and advised to monitor counts, get liver and renal function tests carried out every 2 weeks. On the request of his parents, the child was discharged after 3 days and advised to follow-up in the outpatient department (OPD). After 3 months post-therapy, his HA levels had not reduced. Currently, the baby is under follow-up every 6 months in the OPD.'}", "questions": ["What type of discoloration was noted on the child's nappies and clothing?", "What odor, if any, was observed on the child's skin or urine?", "Were there any reported symptoms such as crying, pain, or changes in urinary stream while the child voided?", "How did the color of the child's urine change after it was voided, and over what time period?"], "ground_truth_arguments": ["reddish discoloration of the nappies and clothes", "no abnormal odor of the skin or urine.", "no history of crying while passing urine, poor urinary stream", "Urine was of normal color when voided but turned black over variable periods spontaneously"]}
{"id": "CaseReportBench:train-344", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'CASE REPORT': 'Patient 1 (UPN 1) is a male who was diagnosed with WAS at the age of 5 months. He presented with incidentally detected thrombocytopenia (23,000/µL) with skin eczema and severe, recurrent otitis media and diarrhea on admission. The second male patient (UPN 2) presented with neonatal thrombocytopenia at birth and received intermittent intravenous immunoglobulin (IVIG). Thereafter he experienced skin eczema and recurrent infections such as cellulitis and pneumonia, until he visited our hospital at 3 months old. Flow cytometric analysis of peripheral blood mononuclear cells (PBMC) for these 2 patients revealed a defect in WASP, leading to the diagnosis of WAS. Subsequently, the nonsense mutations, Arg211stop and Arg13stop, were confirmed by genomic analysis ( 17 ). Before transplantation, these patients were treated with monthly infusions of IVIG as well as supportive treatment but there was no clinical improvement. CBSCT was performed in a laminar air flow room with conventional supportive therapy. The pre-transplantation conditioning regimen for the 2 patients was 1 mg/kg of busulfan intravenously every 6 hr on days -9 through -6. This was followed by 50 mg/kg of intravenous cyclophosphamide on days -5 through -3 and 30 mg/kg of intravenous antithymocyte globulin (ATG) on days -3 through -1. Prophylaxis for acute graft versus host disease (GVHD) included continuous infusion of cyclosporine A beginning on day -1, targeting whole blood levels to be 200 to 400 ng/mL, and 1 mg/kg/dose of methylprednisone every 12 hr on days 5 through 19, and then a taper. The degree of human leukocyte antigen (HLA) match confirmed by high resolution DNA typing between the infused CB and the patients was 4/6 for UPN 1 and 5/6 for UPN 2. Infused cell doses of TNC and CD34+ cells for UPN1 and UPN2 were 6.24×10 7 /kg and 5.08×10 7 /kg for TNC, respectively, and 1.33×10 5 /kg and 4.8×10 5 /kg for CD34+ cells, respectively. T-, NK-, and B-cell enumeration and quantitative immunoglobulin studies (for immunoglobulin G, A, M, D, and E) were performed. Cytofluorographic analyses of lymphocyte subpopulations were performed with murine monoclonal antibodies conjugated to either fluorescein (FITC) or phycoerythrin (PE) and then analyzed by flow cytometry (FACScan; Becton Dickinson, San Jose, CA, U.S.A.). Heparinized venous blood samples from patients and family members were fractionated on a Ficoll-Hypaque gradient to isolate PBMCs. For mutational analysis, genomic DNA was extracted from the peripheral lymphocytes, and 12 WASP gene exons were amplified by polymerase chain reaction (PCR) followed by direct sequencing according to the protocol of Sasahara et al. ( 18 ). Hematopoietic reconstitution following CBSCT was uneventful, with an absolute neutrophil count (ANC) of more than 500/µL on days 31 and 13 and a platelet count of more than 20,000/µL on days 58 and 50, for UPN 1 and UPN 2, respectively. Molecular chimerism studies using the VNTR method showed a complete donor cell type for these patients (data not shown). Acute GVHD did not occur, even after the infusion of HLA 1 or 2 antigen mismatched CB. UPN 1 experienced 1 episode of sepsis with B. cepacia during the pre-engraftment period without any complications. UPN 2 experienced fever and respiratory distress with hypoxemia due to pulmonary edema as well as skin rashes on the trunk in the pre-engraftment period (from days 8 to days 10), which mimics engraftment syndrome. He recovered with oxygen supply via endotracheal tube and fluid restriction as well as methylprednisone therapy. Both patients were clinically well without eczematous skin and recurrent infections at 60 months (UPN 1) and 55 months (UPN 2) post CBSCT. Clinical data regarding CBSCT are shown in Table 1 . The elevated total eosinophil counts and serum IgE levels have been normalized since 7 months post-transplantation in both children ( Table 2 ). Other immunologic parameters including IgG, IgA, IgM, IgD and lymphocyte subsets are summarized at Table 2 . To determine whether the genotype was corrected by CBSCT, we analyzed the WASP gene sequence before and after CBSCT in UPN 1. UPN 1 had a single base substitution (C665T) in exon 7 that results in an amino acid change in codon 211 (Arg211stop) before CBSCT. Following CBSCT, UPN1 had a normal sequence at the mutation site in exon 7 of the WASP gene ( Fig. 1 ).'}", "questions": ["What respiratory distress, hypoxemia, and underlying cause were reported for the patient during the pre‑engraftment period?"], "ground_truth_arguments": ["respiratory distress with hypoxemia due to pulmonary edema"]}
{"id": "CaseReportBench:train-349", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'General and extra-oral examination': \"On general examination, the patients were moderately built with a steady gait. The physical and mental development was also normal. The family history revealed consanguineous marriage of the parents. The parents and other family members were not affected. Medical history was non-contributory. Mother had a full term normal uneventful pregnancy. Natal history revealed that the patients presented with eruptions on the scalp, legs, feet, arms, and hands at birth, for which the parents did not seek any treatment. Subsequently, there was reddening of the palms and soles at 6 months of age, which gradually thickened and became rough and scaly. These symptoms were worse during the winter season. Dermatological examination revealed increased keratinization of the skin of the palmar and plantar surfaces as well as the skin over the dorsal surfaces of the joints of the hands; the keratinized skin was clearly demarcated from adjacent normal skin. Deep fissures were present on the soles of feet. His nails and hair were normal. Patient had a reduced facial height due to resorption of the alveolar ridge. The past dental history revealed that the deciduous teeth had erupted normally, but there had been early shedding, starting at age of 3 years and complete shedding of all deciduous teeth by the age of 6 years. The mother reported that all of the patient's primary teeth were prematurely lost due to hypermobility. There had been normal eruption of all permanent teeth, but gradually the teeth had started becoming mobile and this was followed by exfoliation of the teeth and also described gingival bleeding during brushing and eating, after the eruption of permanent teeth.\", 'Case 2': 'An 11-year-old girl, younger sibling, had mixed dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth with halitosis were present. The radiographic examination using panoramic and periapical films showed severe alveolar bone loss up to the apical third region of the roots of the permanent teeth that were present, giving them the characteristic “floating-teeth” appearance. On lateral cephalogram, there was no evidence of intracranial calcification in both patients. Laboratory investigation was carried out, which included hematological and biochemical assessment. Routine blood investigations and liver function tests were found to be within the normative range of values.', 'CASE REPORTS': \"A 16-year-old boy (case 1) presented to the Department of Dentistry, DR. R. P. Government Medical College, Kangra at Tanda, Himachal Pradesh with the chief complaint of loose teeth and markedly inflamed gingiva, with excessive bleeding and severe halitosis. The patient was referred to our Department for general dental care by the Department of Dermatology where he had been diagnosed with PLS. An overview of the medical history revealed that, by the time the patient came to our department, he was following a therapeutic routine with oral administration of etretinate (Tegison, 10 mg three times daily for 4 weeks) for treatment of PLS dermatologic manifestations. Typical clinical signs of the disease were seen during the child's 1 st year of life. However, he had not sought any treatment until now. The patient had one younger female sibling, 11-year-old girl (case 2) who also showed trait of PLS.\", 'Case 1': 'A 16-year-old boy had permanent dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth, with heavy deposits of plaque and calculus and halitosis were also present. The patient was found to be completely edentulous in the mandibular right quadrant. In the other quadrants, the permanent teeth that were missing were the right maxillary first molar, the right maxillary first premolar and second premolar, the lateral incisors, the central incisors, the left maxillary second premolar. All the permanent teeth that were present exhibited marked mobility. The gingiva adjacent to the teeth appeared red, inflamed and edematous. There was bleeding on probing with deep periodontal pockets. Gingival recession was present in all the teeth. The mucosa of the edentulous area appeared normal. The radiographic examination using panoramic film showed extensive bone loss and areas suggestive of vertical defects.'}", "questions": ["What type of parental relationship is reported in the family history?", "How is the patient's overall medical history described?", "Summarize the cutaneous findings from birth through early infancy, including lesion locations, their evolution, and any seasonal variation.", "Describe the timing, nature, and sequence of primary tooth loss and the subsequent mobility or exfoliation of permanent teeth.", "Provide the age, gender, and condition status of the younger sibling mentioned in the report.", "What were the chief dental complaints of the older individual and where in the document are they documented?", "List the periodontal findings reported for the older individual.", "List the periodontal findings reported for the younger individual."], "ground_truth_arguments": ["The family history revealed consanguineous marriage of the parents. The parents and other family members were not affected", "Medical history was non - contributory", "Natal history revealed that the patients presented with eruptions on the scalp, legs, feet, arms, and hands at birth, for which the parents did not seek any treatment. Subsequently, there was reddening of the palms and soles at 6 months of age, which gradually thickened and became rough and scaly. These symptoms were worse during the winter season", "Case 2 ' : ' An 11 - year - old girl, younger sibling, had mixed dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth with halitosis were present.", "A 16 - year - old boy ( case 1 ) presented to the Department of Dentistry, DR. R. P. Government Medical College, Kangra at Tanda, Himachal Pradesh with the chief complaint of loose teeth and markedly inflamed gingiva, with excessive bleeding and severe halitosis", "The patient had one younger female sibling, 11 - year - old girl ( case 2 ) who also showed trait of PLS. \"", "' A 16 - year - old boy had permanent dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth, with heavy deposits of plaque and calculus and halitosis were also present."]}
{"id": "CaseReportBench:train-53", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as \"disease causing\" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most \"likely damaging\" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}", "questions": ["What steroid replacement regimen was initiated at the time of diagnosis?"], "ground_truth_arguments": ["replacement doses of hydrocortisone and fludrocortisone"]}
{"id": "CaseReportBench:train-124", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}", "questions": ["What evidence of ketonuria was reported in the patient's clinical and laboratory findings?", "What abnormalities were identified by tandem mass spectrometry in the patient's blood acylcarnitine profile, and how do they support a diagnosis of multiple acyl‑CoA dehydrogenase deficiency?", "Which organic acids were found in increased amounts in the patient's urine analysis?", "Which categories of acylcarnitines were reported as elevated in the tandem mass spectrometry results?", "What histopathological features were observed in the muscle biopsy, including staining results that indicate lipid storage and ragged red fibers?", "Were there notable elevations in serum enzymes or metabolic parameters, and what was the overall assessment of liver and renal function?"], "ground_truth_arguments": ["ketonuria", "His tandem mass spectroscopy showed elevated medium - chain acylcarnitine and long - chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol", "Investigations showed severe ketonuria ( creatine kinase, 1271 IU / L, lactate dehydrogenase, 2622 IU / L ). Liver and renal function tests were normal ( aspartate transaminase, 1214 IU / L; alalnine transaminase, 307 IU / L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol / L ). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long - chain acylcarnitines suggestive of multiple acyl - CoA dehydrogenase deficiency. The following levels were obtained from the estimation : hexanoylcarnitine ( C6)- 0.67 μmol / L ( normal range 0–0.23 μmol / L ); adipylcarnitine ( C6DC)- 0.52 μmol / L ( normal range 0.01–0.33 μmol / L ); octanylcarnitine ( C8 ) I-1.2 μmol / L ( normal range 0.01–0.39 μmol / L ); decanoylcarnitine ( C10)-1.71 μmol / L ( normal range 0–0.5 μmol / L ); dodecanoylcarnitine ( C12)-0.63 μmol / L ( normal range 0.02–0.42 μmol / L ); tetradecanoylcarnitine ( C14)- 0.56 μmol / L ( normal range 0.03–0.41 μmol / L ) and tetradecanoylcarnitine ( C14)- 0.59 μmol / L ( normal range 0.01–0.28 μmol / L ). Profiling of urine organic acids showed increased excretion of 2 - hydroxyglutarate ( 2HG ), adipate, arabitol, and 3 - hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin – stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O – positive material suggesting lipid storage."]}
{"id": "CaseReportBench:train-512", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumor was made; biopsy was deferred and hormonal treatment was modified. A 9-year-old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour. The cortisol level was low, and levels of 17 alpha-hydroxyprogesterone, plasma corticotrophin (ACTH), and testosterone were high. Scrotal ultrasound revealed well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses with posterior acoustic shadowing in both testes, in the medial aspects near the mediastinum testis. The right testicular mass measured 1.3×1.1 cm, and the left testicular mass measured 1.5×1.2cm ( Figures 1, 2 ). On colour Doppler, the masses had minimal internal vascularity ( Figure 3 ). The rest of the testes showed normal flow. The epididymis and cord structures were normal. There was no evidence of hydrocoele on both sides. Testicular tumor markers were negative. Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement ( Figure 4 ). In a patient with CAH and bilateral testicular masses that had a typical sonographic appearance, a diagnosis of testicular adrenal rest tumor was made, and biopsy was deferred. Hormonal treatment was intensified, and the testicular masses are followed up. The patient improved clinically, which was associated with a decrease in testosterone and 17 alpha-hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months. Currently, the patient is advised to undergo follow-up ultrasound examinations every 3 months.'}", "questions": ["What growth-related clinical findings, such as stature, were reported for the patient?"], "ground_truth_arguments": ["short stature"]}
{"id": "CaseReportBench:train-92", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': 'A known case of hypertension, asthma and AKU presented to Urology clinic complaining of severe LUTS: obstructive symptoms including poor stream, straining, hesitancy, and incomplete emptying of urinary bladder, in addition to irritative symptoms including frequency, urgency and nocturia. These symptoms started 2 months prior to his current presentation with a history of passing stones during urination and acute urinary retention that was relieved by suprapubic catheterization and cystolitholapaxy for his urinary bladder stones. He also reports blackish discoloration of his urine and history of recurrent urinary tract infections (UTIs). On examination, a urethral stone was felt in the shaft of the penis during palpation, bladder was not full. By digital rectal examination, the prostate was hard with indentation mostly representing palpable stones in the prostatic urethra and para prostatic diverticulum. Other extra genitourinary manifestations due to AKU disease were apparent; including the presence of thoracic lumbar back pain for the past 3 years with an incidental finding of advanced changes of AKU seen in the spine ( Fig. 1 A. KUB), short stature, and black discoloration of the nose and ear cartilages. Fig. 1 Supine KUB (A) showing numerous radiopaque stones at the projection of urinary bladder and prostate, note also advanced changes of alkaptonuria seen in spine, pre-operation non-contrast urinary tract CT (B + C) showing multiple stones in the urinary bladder and prostate. Fig. 1 Laboratory investigations revealed a normal complete blood count, kidney function tests, serum parathyroid hormone, uric acid, calcium, and prostate specific antigen (PSA). The only positive finding was the presence of red blood cells and white blood cells in his urine analysis; however, his urine culture results came back negative. A Kidney, Ureter and Bladder plain film (KUB) and unenhanced urinary tract computed tomography (CT) were done with results as shown in ( Fig. 1 A) and ( Fig. 1 B + C) respectively. Two operative sessions were done to completely clear his stones in the urethra, paraprostatic diverticulum and bladder. During the first operation, cystoscopy revealed multiple urethral, urinary bladder, and left para prostatic diverticulum black stones. His urethral stones were pushed back up to urinary bladder and cystolitholapaxy were used to eliminate urinary bladder stones. A 3-way urethral catheter was inserted into urinary bladder. Another unenhanced urinary tract CT ( Fig. 2 A + B) and pelvic magnetic resonance imaging (MRI) ( Fig. 2 C + D) were taken postoperatively. Fig. 2 Post operation non-contrast urinary tract CT (A + B) showing only few residual stones, the largest on the right side of the prostate and pelvic MRI coronal STIR (C) showing fluid filled diverticulum in the left lateral aspect of the prostate (arrow), axial T2 (D) showing the prostatic diverticulum containing tiny hypointense stone (arrow). Fig. 2 Few days after his first operation, the patient developed pulmonary embolism and started on an anticoagulant (enoxaparin), then the patient course was complicated by clot retention, so suprapubic catheter was inserted and patient was kept on continuous irrigation. Repeat cystoscopy revealed urethral and left paraprostatic diverticulum with multiple black stones that were then fragmented using a pneumatic lithotripter, and evacuated by inserting a 3-ways Foley’s catheter. An unenhanced urinary tract CT ( Fig. 3 ) was taken for comparison with the his baseline CT prior to operation ( Fig. 1 (B + C)). Fig. 3 Axial non-contrast urinary tract CT (A + B) show near completely removal of all stones (residual tiny stone in the prostate, arrow). Fig. 3 The weight of the stones was 78 g, and chemical calculus analysis showed black stones with a composition of 20% uric acids and 80% calcium oxalate. After few days from the last cystoscopy procedure, Foley’s catheter was removed followed by suprapubic catheter removal, after that, patient was passing urine with good stream and discharged home. The patient has been visiting outpatient clinic with a regular follow up visits without any bothersome urinary symptoms.'}", "questions": ["What chronic medical conditions does the patient have?", "What lower urinary tract symptoms did the patient report, specifying obstructive and irritative components?", "When did these urinary symptoms first appear relative to the current presentation?", "What prior urinary events did the patient experience?", "How was the acute urinary retention managed before the current visit, including any catheterization or surgical procedures?", "Did the patient observe any abnormal coloration of his urine, and if so, how was it described?", "What is the patient's history of urinary tract infections, including frequency or recurrence?"], "ground_truth_arguments": ["A known case of hypertension, asthma and AKU presented to Urology clinic complaining of severe LUTS : obstructive symptoms including poor stream, straining, hesitancy, and incomplete emptying of urinary bladder, in addition to irritative symptoms including frequency, urgency and nocturia. These symptoms started 2 months prior to his current presentation with a history of passing stones during urination and acute urinary retention that was relieved by suprapubic catheterization and cystolitholapaxy for his urinary bladder stones. He also reports blackish discoloration of his urine and history of recurrent urinary tract infections ( UTIs"]}
{"id": "CaseReportBench:train-426", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What category of metabolic or genetic syndrome was confirmed in this patient?"], "ground_truth_arguments": ["MELAS syndrome"]}
{"id": "CaseReportBench:train-116", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["What episodes of bilateral arterial thrombosis are reported in the case descriptions?", "What acute arterial thrombosis events are described in the case reports?"], "ground_truth_arguments": ["bilateral thrombosis of the stented SFAs", "acute superficial femoral artery ( SFA ) thrombosis"]}
{"id": "CaseReportBench:train-321", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["What gestational age at birth and any reported pregnancy complications are described for the patient?", "What type of delivery was performed and what factors influenced the decision?", "What details are provided regarding the newborn's birth weight?"], "ground_truth_arguments": ["She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g."]}
{"id": "CaseReportBench:train-315", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': 'SH is a 44-year-old female diagnosed with mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure. After her diagnosis was made, she was initially followed by Neurology; however she was subsequently referred to our cardiomyopathy clinic secondary to progressive left ventricular hypertrophy (LVH) on echocardiogram and the known association between MELAS and cardiac disease. Prior to evaluation by our clinic, she had a clinical diagnosis of MELAS but evaluation by our cardiovascular genetics team yielded positive results for the A-to-G transition at nucleotide 3243 (m.3243A > G) of the mitochondrial genome, with 25% heteroplasmic deleterious mutation in MT-TL1, a mitochondrial leucine transfer RNA gene, the most common mutation underlying MELAS. At the time of presentation to our clinic, SH had carried the diagnosis of MELAS for 11 years and her symptoms had progressed significantly so that she was no longer able to be employed and her husband became her primary caretaker. Her clinical status included multiple medical problems related to her MELAS diagnosis: sensorineural hearing loss, myopathy, bilateral ophthalmoplegia, ptosis, seizures and stroke-like episodes with concern for dementia. Her family history is significant for a 12-year-old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss. In addition to a clinical exam and genetic evaluation, cardiac work-up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non-sustained atrial tachycardia ( Fig. 1 ). From a cardiac imaging perspective, an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub-epicardium of approximately 25–50% in thickness in the inferior segment at the base, inferior to lateral segments at the mid-ventricle and lateral segment of the apex, with sparing of the endocardium and septum ( Fig. 1 A and 1 B). Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes (R > L), and moderate cerebellar atrophy with extensive white matter disease. Monitoring laboratory evaluation yielded no significant abnormalities with the exception of a slightly elevated brain natriuretic peptide of 305 (normal < 200 ng/L). Her liver and kidney functions were normal and there was no hyperglycemia. From a cardiac management perspective, she has been maintained on Atenolol 25 mg twice daily and aspirin 325 mg once daily.'}", "questions": ["What category of mitochondrial disorder was diagnosed in the patient?"], "ground_truth_arguments": ["mitochondrial myopathy , encephalopathy and stroke - like episodes ( MELAS )"]}
{"id": "CaseReportBench:train-463", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'CASE REPORT': 'A 4-year-male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy. His birth was at full-term from an uneventful pregnancy. On detailed history the child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation. Neurological examination revealed mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child. Skeletal, dental, eye/ fundus examination and eye or limb movements were normal. Child had a normal head circumference for his age. Skin examination showed scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face. Chest radiograph and all routine hematological investigations were normal. Electroencephalogram (EEG) was normal. Patient was sent for the MRI of brain. MRI was done on 0.2 tesla Signa (GE systems, USA) MRI with T2W, T1W, FLAIR sequences in all three planes. The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All these clinical and radiological findings were diagnostic of Sjogren-Larsson syndrome.'}", "questions": ["At what age did the skin lesions or ichthyotic rash first appear in the child?"], "ground_truth_arguments": ["since infancy"]}
{"id": "CaseReportBench:train-201", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'A 24‐year‐old woman was admitted to our hospital with mildly impaired consciousness and myoclonus in the extremities. She had been diagnosed with MELAS at 21 years of age. Genetic testing revealed a 3271 T>C transition in the MT‐TL1 gene, clinically confirming the diagnosis of MELAS. After admission to hospital, neurological examination showed myoclonic movement in the extremities, mandible, and trunk. Muscle weakness was detected in the upper and lower limbs bilaterally. A laboratory examination showed increased serum pyruvic acid (2.1 mg/dL) and lactate (75 mg/dL). Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging (Fig. 1 ). Antiepileptic drugs levetiracetam, perampanel, lacosamide, and clobazam were initiated. L‐arginine, coenzyme Q10, and L‐carnitine aimed at supporting mitochondrial energy production were given simultaneously. As the impaired consciousness and myoclonus persisted for 2 weeks, we undertook brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex. Electroencephalography revealed high‐amplitude slow and spiked waves. We diagnosed the patient with non‐convulsive status epilepticus. To control the seizures, propofol was given at a dose of 2.7 mg/kg/h for 12 h and then increased to 5.4 mg/kg/h, with midazolam added at a dose of 2 mg/h. On day 5, the urine appeared brown and arterial blood gas revealed metabolic acidosis (pH 7.261, pCO 2 33.0 mmHg, HCO 3 - 14.4 mmol/L, and lactate 99 mg/dL). Creatinine kinase was elevated at 20,999 U/L. The patient was diagnosed with PRIS. She was transferred to the intensive care unit (ICU) on day 19 of hospitalization. On admission to the ICU, the vital signs were as follows: body temperature, 39°C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths/min; and SpO2, 99% (FiO 2 40%). Laboratory findings showed metabolic acidosis (lactic acid, 99 mg/dL; pyruvic acid, 0.92 mg/dL), creatinine kinase 29,560 U/L, and myoglobin 9,845 ng/mL. We treated her with interruption of propofol and continuous hemodiafiltration for metabolic acidosis. We continued coenzyme Q10, L‐carnitine, and L‐arginine for mitochondrial support for MELAS and antiepileptic drugs including levetiracetam, perampanel, lacosamide, and clobazam. After concurrent treatment of PRIS and MELAS, metabolic acidosis and creatinine kinase gradually decreased after reaching 59,000 IU/L on day 2 of ICU admission. Continuous hemodiafiltration was discontinued on day 11. Tracheostomy was carried out because i.v. midazolam treatment was prolonged to control the status epilepticus. Mechanical ventilation was discontinued on day 25 (Fig. 2 ). After rehabilitation, the patient was discharged on foot.', 'Case Presentation': 'A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus. To control the non‐convulsive status epilepticus, propofol was administered. Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated. The patient was diagnosed with PRIS. We treated her with interruption of propofol. She required mechanical ventilation for 25 days. After rehabilitation, she recovered and was discharged.'}", "questions": ["What were the vital signs (body temperature, blood pressure, heart rate, respiratory rate, and SpO2 with FiO2) recorded on ICU admission?"], "ground_truth_arguments": ["On admission to the ICU, the vital signs were as follows : body temperature, 39 ° C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths / min; and SpO2, 99 % ( FiO 2 40 % )"]}
{"id": "CaseReportBench:train-32", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What findings were reported in the brain MRI and MRA, including any infarctions or lesions?", "What were the chest X‑ray findings at admission?", "What were the electrocardiogram findings at admission and in any prior ECG assessments, noting any abnormalities or cardiac indices?"], "ground_truth_arguments": ["In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found.", "There were no abnormal findings in the chest X - ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67 % and no abnormal findings", "ECG results appeared normal."]}
{"id": "CaseReportBench:train-200", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE DESCRIPTION': \"A 59-yr-old man was admitted to our hospital because he had exhibited progressive lethargy and confusion since the early morning. He had often complained of fatigue over the previous 3 months. Three days prior to presentation, he had eaten a large amount of dog meat at a party, become nauseated, and vomited. The next day, he had eaten chicken and freshwater snails, had again become nauseated, and developed severe vomiting. On the day of admission, he failed to arise at his normal time and exhibited inappropriate behavior and drowsiness. During his childhood, the patient had suffered recurrent abdominal pain and periodic episodes of convulsions, but he had not experienced any seizures in adulthood. On examination, the patient was in a semi-coma; his Glasgow Coma Scale score was 10/15, and he was disoriented in time, place, and person. His vital signs were stable, with a blood pressure of 150/80 mmHg, pulse rate of 84/min, respiratory rate of 24/min, and body temperature of 36℃. Laboratory investigations showed that he had hyperammonemia (143.8 mM), elevated liver enzymes (alanine aminotransferase, 179 U/L; aspartate aminotransferase, 91 U/L), a total bilirubin level of 1.91 mg/dL, and a blood glucose level of 106 mg/dL. His blood urea nitrogen and serum creatinine levels were 17.7 mg/dL and 1.01 mg/dL, respectively. Blood analysis revealed mild leukocytosis (10.41 × 10 3 leukocytes/µL) and a normal hemoglobin level, platelet count, and clotting profile. Serum electrolyte analysis showed mild hypernatremia (149 mEq sodium/L), but serum potassium and chloride levels were within normal range. Results of a toxicology screen were normal. Further investigations revealed no evidence of gastrointestinal bleeding, and computed tomography (CT) and diffusion-weighted magnetic resonance imaging revealed no brain lesions. Abdominal CT imaging did not show any abnormality. The cerebrospinal fluid was normal upon examination. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Despite the administration of a lactulose enema, the patient's serum ammonia level increased to 370 mM and he remained confused, leading us to initiate acute hemodialysis. During the procedure, the patient had a generalized tonic-clonic seizure, for which 1 mg of lorazepam was administered intravenously. The seizure subsided, but the patient continued to move convulsively, leading to several additional injections of intravenous lorazepam. A diagnosis of nonconvulsive status epilepticus was made, and the antiepileptic drug levetiracetam was administered. After the initial session of hemodialysis, the patient's serum ammonia level had decreased to 170 mM, but it soon rose to 228 mM. Plasma and urine amino acid analysis and urine organic acid quantitation were performed. Under suspicion of a urea cycle disorder, arginine (3 g) and sodium benzoate (3 g) were administered via nasogastric tube every 4-6 hr. Dextrose solution (10%) was supplied intravenously, and a protein-free formula was supplied via a feeding tube. By the morning of the next day, the patient's serum ammonia level had decreased to 36 mM. However, because it rose to 107 mM by the afternoon, and the patient was still semi-comatose, hemodialysis was performed one more time. At that time, an electroencephalogram did not show any signs of epileptic discharge. After the second hemodialysis session, the patient's serum ammonia level stabilized at less than 30 mM. A plasma amino acids analysis revealed elevated ornithine (196 µM; normal 19-81 µM), decreased citrulline (3 µM; normal 19-62 µM), and elevated glutamine and lysine. Urine organic acids analysis revealed highly elevated urinary orotic acid (603.5 mg/mg creatinine) and a mild urinary uracil peak. No liver biopsy or genetic analysis was performed. The accumulated evidence led to a diagnosis of late-onset ornithine carbamoyltransferase deficiency. After 5 days, the patient's mental status returned to normal. He continued to receive sodium benzoate (3 g) and arginine (3 g) three times daily. The protein-free formula, which was administered continuously, was gradually changed to increase the dietary protein without a significant rise in serum ammonia levels ( Fig. 1 ). The patient was discharged home after 2 weeks with instructions to continue the medication and formula. His family received special counseling on diet and emergency management before his discharge.\"}", "questions": ["Describe the patient's nausea and vomiting episodes after eating dog meat.", "Describe the patient's nausea and vomiting after consuming chicken and freshwater snails.", "What recurrent abdominal symptoms did the patient experience during childhood?", "What investigations or findings ruled out gastrointestinal bleeding in this case?", "What evidence indicated the absence of chronic liver disease in the patient?"], "ground_truth_arguments": ["become nauseated, and vomited", "nauseated, and developed severe vomiting.", "recurrent abdominal pain", "no evidence of gastrointestinal bleeding", "no evidence of chronic liver disease"]}
{"id": "CaseReportBench:train-78", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Case Report': \"A 13-year-old male child born off a consanguineous marriage presented with complaints of red colored urine since birth, reddish brown-pigmented teeth, and excessive facial hair since 6 months of age. He also had a burning sensation and recurrent blistering over the sun-exposed areas, which healed with scarring and disfigurement of nails since 1-year of age. His birth and mental developmental history were normal. He had an asymptomatic female sibling 8 years of age, and there was no family history of similar complaints. Examination revealed a short statured male child of height 133 cm (< −3 standard deviations). Abdominal examination revealed a protuberant abdomen with hepatosplenomegaly and undescended testis on the left side. He had obvious hypertrichosis over face involving the cheek and forehead, the forearms and multiple bullae over the dorsum of hands, fingers, forearms, and feet with postinflammatory hyperpigmentation and scars over affected skin. Teeth showed brownish-red pigmentation, fluorescent under Wood's lamp. Nails were discolored. Investigations revealed anemia an Hb of 8.3 g/dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis. Urine was port wine color, which fluoresced in Wood's lamp. Porphobilinogen was not detected on Watson–Schwartz test in the urine. Ultrasonography of abdomen confirmed the hepatomegaly, splenomegaly, and the undescended testes with hydrocele on the right side. Mutation analysis was carried out for the affected child and his parents. The affected child exhibited a missense mutation in the UROS gene identified as a transversion of A to G at nucleotide 56, resulting in a substitution of tyrosine by cysteine. The patient showed a homozygous mutant profile, and the parents were heterozygous carriers for the mutation. Based on the clinical presentation with onset in early childhood of a photosensitive disorder with erythrodontia, hypertrichosis, fluorescent red urine, absence of porphobilinogen in urine, and a demonstrated mutation of the UROS gene the child was diagnosed as a case of CEP. He was managed with sun avoidance and liberal use of sunscreen administration. He was referred to the surgical center for definitive management of undescended testis. He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens (HLA) matched donor.\"}", "questions": ["What does the report indicate regarding the patient's birth and mental development?"], "ground_truth_arguments": ["birth and mental developmental history were normal"]}
{"id": "CaseReportBench:train-574", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["For each patient, provide a unique list of all anatomical locations where tendon xanthomas are reported (e.g., Achilles, elbow, plantar foot, finger tendons, toe tendons, knee, etc.).", "For each patient, state whether the report mentions any new tendon xanthomas appearing during the follow‑up period (answer with \"new xanthomas reported\" or \"no new xanthomas\").", "For each patient, for each tendon xanthoma location identified, give the reported longitudinal change (increased, decreased, stable/unchanged) and, if the text specifies, the observation duration; list each location only once.", "For each patient, if surgical debulking of tendon xanthomas is mentioned, list the debulked site(s) and the age at which debulking was performed; omit any output for patients without a debulking report."], "ground_truth_arguments": ["tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years", "acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas", "Tendon xanthomas", "xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas"]}
{"id": "CaseReportBench:train-528", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["What progressive changes in the clitoris were reported in the patient?", "What were the pelvic examination findings concerning the vagina, cervix, clitoris (including any prior surgery), and urethral position?", "What were the ultrasound findings regarding uterine dimensions and ovarian characteristics?", "What abnormalities, if any, were identified in the uterus, ovaries, or inguinal region during the evaluation?"], "ground_truth_arguments": ["gradual enlargement of the clitoris.", "vagina and cervix were healthy, the clitoris was looking normal ( clitoroplasty done in past ) and urethra was mildly displaced posteriorly", "uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count", "hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region"]}
{"id": "CaseReportBench:train-8", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case presentation': 'We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia. She received critical care symptomatic management including mechanical ventilation. The diagnosis was based on a positive urine test for porphobilinogen and confirmed by the presence of a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). This work has been reported in line with the SCARE criteria . A 24 year-old- single female patient was admitted because of right lower abdominal pain and distension for 2 weeks. The pain was colicky, episodic, with no precipitating factors and only relieved after bowel motion. She had no constitutional symptoms of chronic illness. She was not on any medications and her social history was unremarkable. Her menstrual cycle was regular and she was menstruating one day after admission. Physical examination revealed a thin patient in mild pain distress with normal vital signs. Her abdomen was soft and lax with normal bowel sounds. Routine laboratory tests including CBC and renal and liver function tests were normal. Serum transaminases remained normal during her hospital stay. Aspartate aminotransferase (AST, SGOT) range was 18–33 U/L (normal range: 15–37 U/L). Alanine aminotransferase (ALT, SGPT) range was 25–51 U/L (normal range: 14–63 U/L). On admission, level of serum sodium (Na) was normal: 138 mEq/L (normal range 135–145 mEq/L) and remained normal (range: 135–139 mEq/L) until the 5th postoperative day (see below). Plain abdominal X-ray and abdominal computed tomography (CT) showed a distended cecum located in the pelvis with fecal impaction; the rest of the viscera were unremarkable. These findings were consistent with mobile cecum syndrome. The patient was scheduled for laparoscopy and possible laparotomy. The only abnormality during laparoscopy was that the cecum and ascending colon were not attached to posterior abdominal wall. The procedure was converted to laparotomy. Right hemi-colectomy was performed. She was kept on epidural analgesia, intravenous (IV) fluids and nil by mouth for four days and had a smooth post-operative course. After surgery, she received intravenous (IV) 5% dextrose/0.9% NaC) three liters/day (her weight was 48 kg). In addition, her pain was controlled by epidural analgesia of lidocaine and fentanyl. The histology revealed normal colon. On the 5th postoperative day, oral intake was resumed and epidural analgesia was discontinued. Eight hours later, she had a sudden deterioration of consciousness level and became unresponsive with a Glasgow Coma Scale of 7/15. Her pupils were dilated and had a sluggish reaction to light. The patient was immediately intubated, mechanically ventilated, resuscitated, and admitted to the intensive care unit (ICU). Blood work up revealed severe hyponatremia; serum Na: 107 mEq/l with normal renal and liver function tests. Our differential diagnoses for the severe hyponatremia included drug intoxicity, encephalitis, and salt losing nephropathy. Consultations to neurology and psychiatry were made and they advised brain CT scan and magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. These tests and septic work-up were normal. She was extubated two days later. At this stage, she started to complain of acute abdominal pain and developed altered mental status, personality changes, visual and auditory hallucinations with euphoric and aggression episodes despite correction of serum Na. The presence of abdominal pain, neurological and psychiatric symptoms and unexplained severe hyponatremia raised the suspicion of AIP. The diagnosis of AIP was based on the presence of high PBG in the urine (test was done at another center). At no time, her urine was dark. In retrospect, the family history showed that two of her cousins (from mother side) had AIP. The patient condition improved markedly after proper pain control and high carbohydrate intake. We referred her to a higher center where she was found to have a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene (c.760delC p Leu254). There, she received premenstrual regime of IV hematin (heme arginate) 4 mg/Kg body weight/day for three days. She had four recurrent milder attacks in the form of abdominal and back pain and confusion and was treated with similar regime of hematin. Thereafter, she was kept on once monthly prophylactic IV hematin 4 mg/Kg body weight/day for three days. Now, one and a half years after discharge from our service, she is doing fine and on no hematin treatment.'}", "questions": ["What vital sign measurements (e.g., heart rate, blood pressure, respiratory rate, temperature, oxygen saturation) are reported, and how are they described in the document?"], "ground_truth_arguments": ["normal vital signs"]}
{"id": "CaseReportBench:train-111", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}", "questions": ["What were the perinatal characteristics (including gestational age, birth weight, and growth classification) for each twin?"], "ground_truth_arguments": ["A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg ( small for gestational age ).", "the other twin girl was born with a birth weight of 2.4 kg"]}
{"id": "CaseReportBench:train-422", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}", "questions": ["For the first case described, what age in months is explicitly stated as the time when joint swelling first appeared?", "For the second case described, what age in months is explicitly stated as the time when joint swelling first appeared?"], "ground_truth_arguments": ["6 months of age", "7 months of age"]}
{"id": "CaseReportBench:train-350", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': 'This boy was born to nonconsanguineous Chinese parents. He was born at term, weighed 3100 g with good Apgar scores. He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia. He was brachycephalic with hypopigmented hair. He had poor weight gain with swallowing dysfunction and significant reflux disease requiring gastrostomy feeding. He started having orofacial and limb dyskinesias at 1.5 years of age and subsequently developed refractory multifocal epilepsy at 3 years of age requiring multiple antiepileptics and ketogenic diet to control his seizures. Electroencephalogram showed focal and diffuse slowing consistent with background encephalopathic state, with frequent multifocal epileptiform discharges bilaterally. He developed central and obstructive sleep apneas at 3.5 years of age and was initiated on night bilevel positive airway pressure. He was evaluated with magnetic resonance imaging brain scan and chromosomal microarray at 8 months of age, which was normal. Whole-exome sequencing and direct sequencing confirmed that he harbored compound heterozygous missense mutations c.3130C>T (p.Arg1044Cys), c.3430C>T (p.Arg1144Cys), and c.4078G>A (p.Ala1360Thr) in the LRPPRC gene mapped to chromosome 2p21-p16. Parents were carriers of the mutation. His muscle biopsy showed normal muscle architecture with no “ragged-red” fibers, necrotic fibers, or regenerating fibers seen. Cytochrome c-oxidase was positive in most of the fibers. There were no light microscopic or ultrastructural features to support mitochondrial myopathy. Respiratory chain enzymes in skeletal muscle were diagnostic for complex IV defect ( Table 1 ). He is currently 5 years of age, has generalized dystonia, and is mainly chair-bound. He has intermittent eye contact and minimal vocalization. His baseline lactates ranged from 1.5 to 3.6 mmol/L with mild intermittent metabolic acidosis. However, there were no episodes of acute ketosis, glycemic derangements, or any acute stroke-like episodes. The parents’ first child was diagnosed with steroid-resistant nephrotic syndrome at 18 months of age requiring tacrolimus treatment. Their second pregnancy was terminated at 22 weeks’ gestation due to antenatal diagnosis of Ebstein’s anomaly and multiple valvular abnormalities.'}", "questions": ["What feeding problems were reported and how did they affect the patient's weight gain?"], "ground_truth_arguments": ["poor weight gain with swallowing dysfunction and significant reflux disease"]}
{"id": "CaseReportBench:train-144", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE': 'A 56-year-old man, who had been a heavy drinker, presented symptoms of general weakness, abdominal discomfort, diarrhea and weight loss and was admitted to the hospital. On examination, he was found to be cachectic and his abdomen slightly distended with shifting dullness. Laboratory examination revealed a hemoglobin level of 13.1 g/dL; white blood cell count, 17,800/mm 3 ; platelet count, 553,000/mm 3 ; albumin, 2.6 g/dL; total bilirubin, 0.3 mg/dL; GOT, 48 IU/L; GPT, 22 IU/L; and alkaline phosphatase, 117 IU/L. His serum amylase was 856 IU/L and serum lipase 1,077 IU/L. A computed tomographic (CT) scan of the abdomen ( Figure 1 ) revealed evidence of acute exacerbated, chronic pancreatitis, including pseudocysts, one of which was approximately 7 cm in diameter and was located in the tail of the pancreas with adjacent splenic vein occlusion. In addition, right portal vein occlusion, with corresponding perfusion defect and liver infarction, was noted. The patient was treated initially with intravenous fluids, antibiotics and TPN. Two weeks after treatment including TPN, the patient exhibited multiple skin lesions and continued to experience diarrhea more than 10 times daily. These skin lesions were vesiculopustular and erythematous eruptions with scales on the face ( Figure 2A ) and perineal areas. During the following week, the lesions spread to involve the hands and feet ( Figure 2B, 2C ). He became depressed and agitated. In view of typical skin lesions, mental change and protracted diarrhea, we strongly suspected acrodermatitis enteropathica due to zinc deficiency. His serum zinc level was found to have fallen to 17.4 μ g/dL (normal range, 70 to 150 μ g/dL) and, therefore, we initiated therapy with zinc sulfate at 5 mg daily. Three to four days of zinc supplementation produced marked improvement of the diarrhea and, after one week of zinc supplementation, the skin lesions began to alleviate. The patient continued to do well until five weeks after TPN when abdominal pain and fever developed. With strong suspicions of an infected pancreatic pseudocyst, we performed an abdominal CT scan and subsequently a percutaneous pigtail insertion to drain the pseudocyst. Soon thereafter, he felt well with no pain or fever. A repeat CT scan 10 days later showed total collapse of the pseudocyst and resolution of the PVT and liver infarction. On the 74th hospital day, he was discharged without any problem. By this time, his skin lesions had almost healed.'}", "questions": ["What type of zinc supplementation was started for the patient, and what was the general dosing strategy?", "What was the observed timeline for improvement of gastrointestinal symptoms and skin manifestations after beginning zinc supplementation?"], "ground_truth_arguments": ["we initiated therapy with zinc sulfate at 5 mg daily . Three to four days of zinc supplementation produced marked improvement of the diarrhea and , after one week of zinc supplementation , the skin lesions began to alleviate ."]}
{"id": "CaseReportBench:train-223", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case Report': \"The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. The proband (III-1) ( Fig. 1 ) was a 37-year-old man with severe dizziness and double vision. He had first experienced visual and gait disturbances at 10 years of age. The neurological examination performed on admission revealed mild disturbance of cognitive function (Revised Wechsler Adult Intelligence Scale: total IQ=73, performance IQ=58, verbal IQ=91). Neurological disturbances were observed including bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze-evoked nystagmus, and dysarthria. The light reflex was prompt. No disturbances in cranial nerves I, VII, VIII, and XII were detected. Tremor appeared in his neck, but other involuntary movements including palatal myoclonus were not observed. While his upper and lower limbs showed no paralysis, they exhibited severe cerebellar ataxia and hypotonia. No abnormal findings were detected in his deep tendon reflex and sensory system. Ophthalmological examination revealed atrophy of the optic nerve, but there were no pigmentation changes of the retina. Blood and cerebrospinal fluid analyses were normal. Ergometer exercise did not up-regulate his serum lactate and pyruvate. Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1-weighted imaging, and high signal intensities on T2-weighted imaging, suggesting degeneration ( Fig. 2C and D ). The patient was diagnosed as having LHON plus olivocerebellar degeneration. Although the thyrotropin-releasing drug taltirelin did not relieve his symptoms, adenosine triphosphate disodium reduced his dizziness. The patient's mother (II-2) and uncle (II-3) also had optic neuropathy, but other neurological abnormalities such as ataxia and dystonia were not observed. The patient's mother has a history of subarachnoid hemorrhage. MRI of his mother disclosed mild atrophy of the optic nerve ( Fig. 2E ), pons, and cerebellum ( Fig. 2F-H ). No signal changes were observed in the inferior olivary nucleus ( Fig. 2F-H ). We were unable to confirm the detailed clinical information of the proband's grandmother (I-2).\", 'Mutation analyses of mtDNA': \"Blood samples were obtained from the patient and his mother with their informed consent, and the methods used were approved by the institutional review board of Tottori University Hospital. Both mtDNA and genomic DNA were extracted by standard procedures. The polymerase chain reaction (PCR) was carried out using the primers 5'-CCTCCCTACTATGCCTAGAAGGA-3' and 5'-TTTGGGTTGTGGCTCAGTGT-3' for ND4, including 11778G analysis, and 5'-AGTTCAGACCGGAGTAATCCAG-3' and 5'-AGGGTTGTAGTAGCCCGTAG-3' for ND1 . The primer set for ND4 was designed to identify G11778A mutations, which is the main mutation for LHON. The primer set for ND1 was designed to detect not only the T3394C mutation as a minor mutation for LHON but also an A3243G mutation that is frequently detected in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. PCR products that included the previously reported candidate abnormal points were analyzed by capillary electrophoresis using an automated DNA sequencer. The G11778A and T3394C mutations were identified, while the A3243G mutation was not detected. The mutations in the mtDNA were confirmed by performing PCR-restriction fragment length polymorphism (RFLP), in which the PCR products were digested using either HaeIII (for T3394C) or Tsp45I (for G11778A). In order to quantify the heteroplasmic mutation of G117 78A, we prepared vector constructs including 11778G or 11 778A, and semiquantitative analyses of G11778A were performed using a mixture of each with several rate standards (described in Fig. 4 ). Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr-to-His amino acid substitution in ND1. PCR-RFLP data revealed that the T3394C mutation present in both the proband (III-1) and his mother (II-2) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg-to-His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR-RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92% heteroplasmic G11778A mutation, and II-2 had a 70% heteroplasmic G11778A mutation ( Fig. 4C ). Established genetic abnormalities associated with cerebellar ataxia including polyglutamine diseases were not found.\"}", "questions": ["What neurological symptoms affecting sight and walking were reported, and at what age did they first appear?", "What ocular motor abnormalities were reported, including any gaze palsies and types of nystagmus?", "Which specific gaze palsy was identified in the examination?", "What characteristics of the nystagmus (e.g., direction, trigger) were described?", "What symptoms of dizziness and double vision were reported, and how severe were they?", "What observations were made regarding the patient’s light reflex?", "Were any pigmentation changes of the retina noted in the ophthalmologic assessment?", "What clinical and imaging findings suggest degeneration of the optic nerve?"], "ground_truth_arguments": ["visual and gait disturbances", "horizontal gaze palsy, gaze - evoked nystagmus", "atrophy of the optic nerve", "severe dizziness and double vision", "visual and gait disturbances", "bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze - evoked nystagmus", "The light reflex was prompt.", "atrophy of the optic nerve", "no pigmentation changes of the retina", "Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ),"]}
{"id": "CaseReportBench:train-343", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["What are the patient’s age, sex, and body weight?", "What gastrointestinal complaints (such as abdominal pain, vomiting, or loss of appetite) did the patient report, and over what time period did they occur?", "Describe the seizure activity experienced by the patient, including the type of seizure and its duration.", "What neuromuscular and respiratory findings were noted (e.g., pattern of limb weakness, progression, and presence of respiratory distress), and how long did they develop?", "Which specific exposures or injuries (e.g., snakebite, chest pain, ingestion of toxins, or blunt trauma to the neck/abdomen) were explicitly stated as absent in the history?"], "ground_truth_arguments": ["A 17 - year - old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen"]}
{"id": "CaseReportBench:train-386", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 52-year-old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene. Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme. We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme. After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["Approximately how old is the patient?"], "ground_truth_arguments": ["52 - year - old"]}
{"id": "CaseReportBench:train-61", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE REPORT': 'A 37-year-old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous (IV) drug abuser that required a permanent indwelling venous catheter for his repeated attacks; so, he had a port since 9 months ago and received pethidine via that port during the attacks. On admission, a chest computed tomography revealed multiple cavities in both lungs. A large mobile veg on anterior leaflet of tricuspid valve commissure (TVC) with severe TR was also demonstrated in his transthoracic echocardiography. After starting antibiotic therapy and removing the port, the patient underwent TV replacement. In the day of surgery, prior to induction, all standard monitorings were applied; radial artery line and subclavian central venous (CV) line was also indwelled after induction. Premedication was consisted of incremental doses of fentanyl and midazolam. We used propofol and atracurium for induction. Maintenance of anesthesia was done by propofol, atracurium, midazolam and fentanyl. Following sternotomy and heparinization, cardiopulmonary bypass (CPB) was initiated. The patient cooled to 32–34°C. Myocardial protection was provided by hypothermic antegrade blood cardioplegic. The TV was replaced. After 70 min of CPB, separation from CPB was achieved, and heparin was reversed by protamine. Rewarming and weaning from CPB was uneventful. Four units of packed cell were given during CPB; Hct was maintained about 30%. Postoperatively, in Intensive Care Unit (ICU), the patient was extubated in 6 h. We started parenteral carbohydrate as dextrose 50% to prevent AIP attack, and the patient was encouraged to become per oral (PO) as soon as possible. Finally, he was discharged from ICU on day 2 after surgery. AB therapy was continued for several weeks. By providing adequate IV crystalloid fluids, we had prevented any dehydration. The patient was cautiously observed for any symptoms of AIP attack. Throughout his stay in ICU, he had no symptoms such as abdominal pain, dark urine, and neurologic deficit.'}", "questions": ["What gastrointestinal, urinary, or neurological symptoms were reported during the patient's ICU stay?", "List any signs or symptoms that could indicate an acute intermittent porphyria attack that were observed while the patient was in the ICU."], "ground_truth_arguments": ["no symptoms such as abdominal pain, dark urine"]}
{"id": "CaseReportBench:train-533", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': \"A 22-month-old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control. She was born at full term through normal vaginal delivery. She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time. Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement ( Fig. 1 ). Developmental regression was similar to that in GM2 gangliosidosis, such as Tay-Sachs disease and Sandhoff disease. The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A (%) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol/hr/mg (reference range, 620–1,000 nmol/hr/mg) and 74.3% (reference range, 55%–72%), respectively. Based on these findings, the patient was diagnosed with Sandhoff disease. However, the patient did not show cherry red spot on fundoscopy. At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable ( Fig. 2 ). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale (MAS). Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross-motor domain, by 3 months in language and fine motor domain, and by 2 months in personal-social interaction domain in the Denver Developmental Screening Test II. Dietary assessment revealed that the patient irregularly ingested a soft and blended diet of 70–130 kcal, five times a day, and the mean eating duration was approximately 1 hour. She had difficulty in eating and she showed signs of aspiration (e.g., coughing, gagging). Moreover, she had a poor feeding posture with inadequate trunk and head support. Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas. The patient underwent videofluoroscopic swallowing study (VFSS), and was given barium-containing free water, yogurt (thick liquid), and rice porridge (soft). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time (1.3 seconds) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing ( Fig. 3 ). The patient's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight-for-height Z-score (−0.3) was in the 15th–50th percentile of the World Health Organization (WHO) growth standards. Nutritional evaluation showed that the patient needed a regular daily intake of 989 kcal. However, she could only consume 700 kcal/day, which was less than the required caloric intake. The patient was given supplementary balanced nutrition twice a day. The patient received an intensive dysphagia rehabilitation program for 30 minutes a day, five times a week, for 6 weeks, and it comprised both direct and indirect interventions, such as oromotor facilitation, thermo-tactile stimulation, and lip strengthening, and compensatory techniques, such as postural modification and alteration of the feeding utensil to facilitate swallowing. She was given anti-spasticity drugs for managing spasticity and achieving a stable posture during feeding. After the treatment, she was fed in a semi-reclined position, which reduced the signs of aspiration and the amount of food or liquid leakage from the mouth. However, her nutritional status showed no improvement, with her daily calorie intake decreasing to 600 kcal/day after 4 weeks of admission. At 6 weeks postadmission, her total intake further decreased to 392 kcal/day. Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight-for-height Z-score (−1.6) decreased to the 3rd–15th percentile of the WHO growth standards, which was a sharp decrease of one major percentile line in a short period. Gastrostomy was therefore recommended, but her parents refused the procedure. She was then referred to another hospital for treatment of deconditioning due to dehydration, and she received gastrostomy.\"}", "questions": ["What difficulties did the patient encounter while swallowing, and were any related respiratory symptoms or extended feeding times reported?", "Can you describe the general texture and scheduling of the patient's meals?", "Were any protective reflexes or respiratory signs noted while the patient was eating?"], "ground_truth_arguments": ["swallowing difficulty", "symptoms of aspiration while swallowing and prolonged feeding time", "irregularly ingested a soft and blended diet", "She had difficulty in eating and she showed signs of aspiration ( e.g., coughing, gagging )"]}
{"id": "CaseReportBench:train-156", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine. She was born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively. As a 3-week-old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed. At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day. Physical examination revealed multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back. The spleen was of normal size and physical and intellectual development was normal. Again, moderate hemolytic anemia was also found (red blood cells: 3.68 × 10 6, hemoglobin: 10.6 g/dl, hematocrit: 33.0%, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G/DL, platelets 124 × 10 3 ml, white blood cells: 3.6 × 10 3, reticulocytes: 58 (5-15)), but did not require a blood transfusion. Further laboratory investigations were as follows: urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal. Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable. Now, aged 14 years, the severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands. Using all available measures to protect herself from the sun (hat, eyeglasses, cosmetic camouflage, and long sleeves) has not succeeded in protecting her from the mutilating effects of sun. This has caused scarring of her skin at sun-exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp. In addition, she has restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust. Moderate hypertrichosis on the back of the neck was also noted and her teeth have progressively stained brownish-red. The results of the biochemical investigations are summarized in Table 1 . Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High-pressure liquid chromatography of the urine demonstrated 85% of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617. These results confirmed a diagnosis of CEP. Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T>C (p.Cys73Arg) in exon 4 and c.683c>T (p.Thr228Met) in exon 10. These missense mutations have previously been described, where the patient had a moderate to severe phenotype.'}", "questions": ["What episodes of hemolytic anemia did the patient have, including any blood transfusions administered and the severity noted across her hospital admissions?", "What types of laboratory abnormalities were noted during the episode of moderate hemolytic anemia at age six, and was a blood transfusion required?"], "ground_truth_arguments": ["As a 3 - week - old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed", "moderate hemolytic anemia was also found ( red blood cells : 3.68 × 10 6, hemoglobin : 10.6 g / dl, hematocrit : 33.0 %, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G / DL, platelets 124 × 10 3 ml, white blood cells : 3.6 × 10 3, reticulocytes : 58 ( 5 - 15 ) ), but did not require a blood transfusion"]}
{"id": "CaseReportBench:train-388", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["What was the dosing regimen and duration of heme arginate therapy administered to the patient?"], "ground_truth_arguments": ["heme arginate ( 3 mg / kg / day for 4 days )"]}
{"id": "CaseReportBench:train-614", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Presentation': \"Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment. A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5 th percentile), weight 3000 g (<5 th percentile), and head circumference 36.5 cm (5–10 th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance. Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative. The laboratory tests were as follows: serum sodium 102 meq/lit and serum k + level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1 . Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern. Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed. On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25 th percentile), weight 9.5 kg (10–25 th percentile) and head circumference 46 cm (25 th percentile); her neurodevelopment was appropriate for age.\"}", "questions": ["What was the age of the infant at the time of presentation?"], "ground_truth_arguments": ["45 days old"]}
{"id": "CaseReportBench:train-28", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Chief complaints': 'A 52-year-old female presented with a sudden onset of right-sided numbness and weakness that was accompanied by a left temporal cluster-like headache. No fever or prodromal infection was found at disease onset.', 'Imaging examinations and history of present illness': 'MRI demonstrated a lamellar left parietal lobe lesion predominantly involving the cortex, with hyperintensity on both diffusion-weighted imaging and fluid-attenuated inversion recovery (Figure 1 ). The apparent diffusion coefficient map revealed a preserved, isointense signal. No abnormalities were found by susceptibility weighted imaging or magnetic resonance angiography and venography (Figure 1 ). Due to the stroke-like onset pattern and MRI features, further thrombophilia screening was performed and showed decreased protein S activity. A diagnosis of cortical venous thrombosis was first proposed. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) was also considered but temporarily excluded because of the incomplete manifestation and lack of genetic evidence. Anticoagulation therapy was initiated, and follow-up was performed to maintain the international normalized ratio (INR) within the target range. Two months later, the patient was readmitted for subacute cognitive impairment. She was unable to identify and communicate with family members; she also had difficulty understanding questions or instructions and instead responded by repeating the word \"nothing\". During hospitalization, a secondary generalized seizure occurred, initially with eyes gazing to the right and then convulsion developing, which lasted for approximately 10 s before self-alleviation. Neurological examination suggested transcortical sensory aphasia, with fully covered limb strength. Blood tests and CSF examination were normal; INR was 2.21. On repeated MRI, new lesions were identified in the left temporal lobe and were also detected 10 days later in the right temporal lobe on radiological follow-up (Figures 1 and 2 ). Although the MRI signal characteristics are consistent with the initial findings, the original lesion in the left parietal lobe had been alleviated, with cortical atrophy. We further conducted magnetic resonance spectroscopy (MRS), which revealed markedly elevated lactate (Lac) concentrations in the regions of interest in the left temporal lesion (Figure 1 ). Mitochondrial encephalopathy was diagnosed, and genetic testing using peripheral blood was performed. However, DNA testing for frequent MELAS and myoclonic epilepsy with ragged red fibers syndrome mutations were negative. Because of the lack of symptoms of muscle weakness or pain, the patient declined our suggestion of performing a muscle biopsy. Anticoagulation therapy was terminated, and levetiracetam (1000 mg/d) was administered. At 3 mo after her second admission, the patient was experiencing involuntary movement in her left limbs, with repetitive flexion/extension. An MRI scan showed a hyperintense signal abnormality in the right parietal lobe (Figure 2 ). Brachial biceps biopsy was performed. Histopathology revealed no abnormalities, and no necrotic or regenerating fibers were observed; ragged-red fibers and intense succinate dehydrogenase activity were not detected. Nonetheless, complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a heteroplasmy level of 69.6%, in the mitochondrial complex I subunit gene MT-ND3 . In contrast, this mutation was not found in her peripheral blood cells.', 'Personal and family history': 'The family and personal history was unremarkable.', 'Physical examination upon admission': 'On physical examination, the height and weight of the patient were 154 cm and 56 kg, respectively. Vital signs were normal, as were heart, lung and abdominal exami-nations. Neurological examination showed intact mental status, with normal speech and comprehension. Mild 4/5 right-sided hemiparesis was present with normal tone in both the arm and leg, though no other focal neurological deficits were found. After admission, she complained of discomfort and tingling in the right leg, after which a generalized tonic-clonic seizure for 3 min occurred before it was stopped by a bolus of intravenous diazepam.', 'CASE SUMMARY': 'We report a 52-year-old woman with recurrent stroke-like episodes carrying the m.10158T>C mutation in the MT-ND3 gene, which is also responsible for fatal infant-onset Leigh syndrome. Despite the common mutation, the present case featured a distinct clinical and neuroimaging manifestation from Leigh syndrome. This patient presented with sudden onset of right-sided hemiparesis and hemilateral sensory disturbance accompanied by a left temporal cluster-like headache and later developed epilepsy during hospitalization, with no other signs suggestive of myopathy, lactate acidosis, or other systemic symptoms. Brain magnetic resonance imaging revealed variable lesions involving multiple cortical and subcortical regions. Furthermore, a negative genetic test obtained from peripheral blood delayed the diagnosis of mitochondrial disease, which was eventually established through second-generation DNA sequencing using biopsied muscle.', 'Laboratory examinations': 'Laboratory tests, including D-dimer, lactic acid, and serum autoantibody levels, as well as thyroid function and tumor markers indicated no apparent abnormalities. Glucose tolerance and lactic acid movement tolerance tests were normal. A lumbar puncture was performed, and her open intracranial pressure was 180 mm H 2 O. Cerebrospinal fluid (CSF) testing showed that cell counts and protein, glucose, chloride, monoclonal antibody, adenosine deaminase, and lactate dehydrogenas levels were within normal ranges.'}", "questions": ["What type of genetic abnormality is reported in the mitochondrial genome, and which mitochondrial gene is affected?"], "ground_truth_arguments": ["m.10158T > C mutation in the MT - ND3 gene"]}
{"id": "CaseReportBench:train-355", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}", "questions": ["What changes in urine color are described in relation to physical activity or exertion?"], "ground_truth_arguments": ["brown colored urine after exertion"]}
{"id": "CaseReportBench:train-162", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'CASE REPORT': \"In 1986, a previously healthy 18-year-old male presented to our hospital with a 1-week history of fever, headache and vomiting. Meningism, but no focal neurological signs, was noted on examination. Lumbar puncture was performed, revealing slight elevation of protein in the cerebrospinal fluid (CSF) but no increased cell count. Over the next few days, right-sided weakness developed. Electroencephalogram demonstrated left parieto-occipital focal slowing. Results of T1/T2-weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area. The patient was commenced on acyclovir, but herpes serology came back negative. When generalized tonic-clonic seizures ensued, anticonvulsant therapy with carbamazepine was established. The patient was finally discharged with a provisional diagnosis of viral encephalitis, although no causative agent was found. No residual neurological deficits persisted. In 1989, hearing impairment was first documented and ascribed to the previous encephalitis. The following years saw recurrent admissions for seizures, and sodium valproate was added. The patient's functional status deteriorated progressively. In 1999, he was diagnosed with diabetes mellitus, requiring insulin straightaway. The patient's sister was admitted to our department in October 2010 with gross oedema of the legs. Her medical history included diabetes and sensorineural deafness. Advanced renal impairment was noted. In view of her phenotype, we suspected maternally inherited diabetes and deafness (MIDD). The 3243A>G mutation in the MT-TL1 gene of the mitochondrial DNA (mtDNA) was subsequently demonstrated in blood leucocytes, confirming the diagnosis. When her brother was admitted in October 2011 for anorexia, we re-evaluated his past medical notes. In the initial CSF analysis, no lactate levels had been checked. Electrocardiogram showed Wolff–Parkinson–White syndrome. Macular dystrophy, but no signs of diabetic retinopathy, was found on fundoscopy. CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto-occipital hypodensity, likely representing a previous stroke-like event (Fig. 1 ). Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) was deemed a likely explanation for his multi-systemic disease and was confirmed by demonstration of the 3243A>G transition in blood and urine. The heteroplasmy rate (the mixture of normal and mutated mitochondrial DNA) was 50 and 90%, respectively. Anticonvulsant therapy was switched to levetiracetam and treatment with coenzyme Q 10 was started. The patient now lives in a nursing home. Follow-up at our unit has been arranged. Figure 1: Cerebral computed tomography of a 40-year-old man showing generalized cerebral atrophy, bilateral basal ganglia calcification (asterisks) and a left parieto-occipital hypodensity (arrow).\"}", "questions": ["What gastrointestinal symptoms were reported during the patient's initial hospital admission?", "What symptoms were reported when the brother was admitted in 2011?"], "ground_truth_arguments": ["vomiting.", "anorexia"]}
{"id": "CaseReportBench:train-157", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["What specific diagnosis was assigned to the patient for her adrenal insufficiency?", "According to the report, which condition was identified as the cause of the patient’s adrenal insufficiency?", "How is the patient’s adrenal insufficiency described in terms of the underlying disease?"], "ground_truth_arguments": ["She was diagnosed as having adrenal insufficiency caused by CLAH ."]}
{"id": "CaseReportBench:train-478", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A one-and-half year old boy presented with generalized scaling over whole body and redness over both cheeks. There was a history of consanguineous marriage and prolonged labor and baby was delivered by normal vaginal delivery. The birth weight of the baby was 2.3 kg and the length of the baby was 36 cm. There was no history suggestive of collodion membrane. Scaling started from 3 weeks of age and had a history of exacerbation in the winter and improvement in summer. Immunization was completed according to the immunization schedule. There was no family history of similar kind of illness. There was no history of any drug intake prior to the scaling or atopic diathesis. On examination there was fine white to brown scaling over the whole body without any spared area with glistening surface over palms and soles with involvement of flexures. On the scalp fine whitish-grey and grayish brown scaling was present and in some areas there was thick crusting which on removal revealed a moistened surface. On the frontal scalp margin, there were large grayish-brown ichthyotic scales. Both the cheeks were erythematous along with scaling and scales also involved the upper eyelid, upper lips and over the nose. There was no abnormality in the eyes except mild ectropion. There was no evidence of seborrheic blepharitis. Left-sided cryptorchidism was present for which the patient was referred to pediatric surgery and they have suggested waiting for another 6 months after which they would suggest surgical intervention. Ophthalmological examination was done and no abnormality found. Blood investigations, chest X-ray, urine examination showed no abnormality. Histopathological examination was done which revealed mild hyperkeratosis. As it is not confirmatory and does not help in making the diagnosis, we made a diagnosis of erythroderma due to X-linked ichthyosis as there were components of history of consanguinity and prolonged labor and examination showed cryptorchidism and generalized scaling with flexural involvement. The patient was prescribed emollient and urea 10% cream and after 4 weeks he showed improvement in scaling and oral retinoid was not needed.'}", "questions": ["What is the child's age, gender, and the primary skin findings observed at presentation?", "What information is given about the parents' relationship and the circumstances of labor and delivery?", "What were the birth weight and length of the child?", "Was a collodion membrane noted at birth, and if so, what was its description?", "At what age did the scaling start, and how does it change with the seasons?", "What is the status of the child's immunizations relative to the recommended schedule?", "Describe any family history of similar skin conditions or illnesses.", "Detail any drug intake prior to the onset of scaling and any history of atopic diathesis."], "ground_truth_arguments": ["A one - and - half year old boy presented with generalized scaling over whole body and redness over both cheeks. There was a history of consanguineous marriage and prolonged labor and baby was delivered by normal vaginal delivery. The birth weight of the baby was 2.3 kg and the length of the baby was 36 cm. There was no history suggestive of collodion membrane. Scaling started from 3 weeks of age and had a history of exacerbation in the winter and improvement in summer. Immunization was completed according to the immunization schedule. There was no family history of similar kind of illness. There was no history of any drug intake prior to the scaling or atopic diathesis."]}
{"id": "CaseReportBench:train-57", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'CASE REPORT': 'A 4-year-old female patient with a nasal anomaly was admitted to our outpatient clinic. She was born 2300 g prematurely on her 37 th gestational week from a 34-year-old mother with a history of five pregnancies, two still births and two abortions. On her physical examination, she had a left-sided supernumerary nostril and cliteromegaly. Her laboratory studies revealed low levels of androstenedione and her history showed that she had medical therapy for 1 year for her congenital adrenal hyperplasia. No additional anomaly except patent foramen ovale was detected in her work-ups. Paranasal sinus computed tomography study revealed that her left-sided accessory nostril opened to the left nasal cavity. The patient was operated, the opening of the supernumerary nostril to the nasal cavity was obliterated and the widened nostril was narrowed by excisions from the alar ground and lateral side. A revision toward the nostril asymmetry is planned 1 year after the operation.'}", "questions": ["Describe the nasal anomaly, specifying its type and laterality, that was identified in the patient.", "According to the paranasal sinus computed tomography, where does the accessory nostril open?"], "ground_truth_arguments": ["left - sided supernumerary nostril", "Paranasal sinus computed tomography study revealed that her left - sided accessory nostril opened to the left nasal cavity"]}
{"id": "CaseReportBench:train-413", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}", "questions": ["What therapeutic approach was selected for the patient's acute intermittent porphyria, and what considerations guided that choice?", "How did regional availability of heme arginate influence the management strategy for the patient?"], "ground_truth_arguments": ["Because heme arginate is not available in mainland China , the patient was treated with intravenous glucose infusion ( 50 % ) ."]}
{"id": "CaseReportBench:train-186", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Presentation': 'A 17-year-old intellectually disabled boy was admitted to our neurology clinic due to an abnormality in his hand and difficulty in walking. He had a feeling of fear and trembling of his legs when climbing the stairs. His symptoms had begun when he was 4 years old and worsened until his parents noted and brought him to the clinic. He had diarrhea and jaundice during infancy and underwent phototherapy 3 times until the jaundice was completely resolved. Also, he had bilateral cataracts at the age of 12. At the age of 14, he had a car accident that caused a fracture in his skull. He had no history of cardiovascular or pulmonary diseases, and there was no genetic disorder in his family history. He was the fourth child of the third-degree consanguineous marriage and was born at term after a normal pregnancy, and his development was normal. At the time of admission to the clinic, his weight was 54 kg (11.70 percentile), height was 158 cm (1.07 percentile), and head circumference was 56 cm. Physical examination revealed ataxia, dysarthria, and spastic paraparesis with pyramidal signs more prominent on the right lower extremity. Eye examination and other neurological tests were performed because of his symptoms such as visual impairment, peripheral neuropathy, hallucinations, depression, and delusion and yielded negative results. There was no sign of palpable xanthoma in any of his tendons even in Achilles tendon. In the examination of his right hand, the fourth and fifth interphalangeal joints were flexed, and the third and fifth metacarpophalangeal joints were extended, which was found to be the result of presence of small xanthoma in the tendons of the right hand ( Figure 1 ). Electromyography and nerve conduction velocity (EMG/NCV) revealed no evidence of myopathy or neuropathy, and the motor and sensory conduction velocities were normal. Laboratory tests showed a normal cholesterol level in the serum (162 mg/dL) and a normal total serum bile acid level (10 µmol/L). Other laboratory test results are shown in Table 1 . Brain magnetic resonance imaging (MRI) demonstrated diffuse and focal cerebral and cerebellar white matter abnormalities ( Figure 2 ). The genetic study was performed by the next-generation sequencing (NGS) method, and the results were confirmed by the Sanger sequencing method. The apparent homozygous variants in the NM_000784.4(CYP27A1) : c.803G>A (p.Trp268*) and NM_032382.5(COG8) : c.1073G>A (p.Arg358Gln) in the CYP27A1 and COG8 genes were found which are pathogenic based on American College of Medical Genetics (ACMG) classification. 9, 10 Therefore, our patient was diagnosed with CTX and a mutation on COG8 gene . In due course, we started CDCA 810 mg daily (15 mg/kg/day). In a 3-month follow-up, he had a cholesterol level of 96 mg/dL and a bile acid level of 4 µmol/L which both were normal, and the symptoms had been under control. Due to the absence of seizures, he did not receive any additional treatment. Since then, he was followed every 3 months with a physical examination and laboratory tests including cholesterol level. In addition, the patient’s family was consulted on how to respond correctly to his needs, due to his intellectual disability.'}", "questions": ["What was the patient's weight at admission and its corresponding percentile?", "What was the patient's height at admission and its corresponding percentile?", "What was the patient's head circumference at admission?"], "ground_truth_arguments": ["his weight was 54 kg ( 11.70 percentile ), height was 158 cm ( 1.07 percentile ), and head circumference was 56 cm"]}
{"id": "CaseReportBench:train-534", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["When did the patient first notice increased facial hair, and were there any additional areas of hair growth reported?", "How was the patient's hirsutism assessed, and was a standardized scoring system such as the Ferriman–Gallwey method used?"], "ground_truth_arguments": ["developed facial hair when she was 8 - year - old. There was hair growth in the chest region", "hirsutism was evident. Her simplified Ferriman – Gallwey score for hirsutism was 9 ( ≥3 )."]}
{"id": "CaseReportBench:train-125", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case report': 'Phenotypic female twins (A, B) were born at 36+2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g (<10 percentile) in A and 2,040 g (10 to 25 percentile) in B, height was 43 cm (10 to 25 percentile) in A and 44 cm (10 to 25 percentile) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit (NICU). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17-OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17-OHP, elevated ACTH (A, 4,379.2 pg/mL at 23 days of life; B, 11,616.1 pg/mL at 29 days of life), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng/mL/hr). However, the level of plasma cortisol before treatment were normal (8.71 µg/dL initially, 7.11 µg/dL in 2nd sample) in patient A, but low (1.5 µg/dL) in patient B. The results of endocrinologic investigation are shown in Table 1 . The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography (CT) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level (132 to 139 mmol/L) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia (129 to 133 mmo/L) and further evaluation for skin hyperpigmentation. She was treated with oral supplementation of sodium (0.8 to 0.9 mmol/kg) at 11 to 35 days of age, and she discharged from the hospital with normal sodium level after tapering off sodium supplementation at 37 days of age. Patient A was admitted at 38 days of age with adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration. Clinical findings of patient A were suggestive of CLAH and prompted us to order a gene analysis in both twins. Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C>T (p.R182C) in exon 5 and c.722C>T (p.Q258X) in exon 7 ( Fig. 1 ). Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms, except hyponatremia, but she was also diagnosed with CLAH with the same StAR gene mutation with patient A. The results of gene analysis of parents showed heterozygous for the mutations in the StAR gene; the heterozygous gene mutations; c.772C>T in the mother, and c.544C>T in the father, were documented. They showed suboptimal levels of hormone despite of administration of 20 mg/m 2 /24-hr of hydrocortisone, dose of hydrocortisone was increased up to 30 mg/m 2 /24-hr. Both patients have been under steroid supplementation (fludrocortisones 0.2 mg daily in 2 divided doses, and hydrocortisone 12 mg daily in 3 divided doses) at 14 months of age. They showed normal development except retarded physical growth, and hormones and electrolyte levels on follow up are shown as Table 1 . Body weight was 8.8 kg (3 to 10 percentile) in patient A, 9.4 kg (10 to 25 percentile) in patient B, body length was 73.7 cm (3 to 10 percentile) in patient A, 75.4 cm (10 to 25 percentile) in patient B at 14 months of age. They had been regularly followed.'}", "questions": ["What symptoms of adrenal insufficiency did patient A exhibit at 38 days of age?"], "ground_truth_arguments": ["poor oral intake, vomiting, lethargy and dehydration"]}
{"id": "CaseReportBench:train-449", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}", "questions": ["What neuromuscular symptom did the patient experience during her episodes of abdominal pain and vomiting?"], "ground_truth_arguments": ["muscle weakness during attacks."]}
{"id": "CaseReportBench:train-348", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': 'The patient was a 41-year-old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age. He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure. His family history was not remarkable. He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age. Three months later, he was admitted to our hospital due to impaired consciousness and vomiting. A neurological examination showed gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities. However, no ophthalmoplegia, hearing loss, or muscle weakness were detected. His mini-mental status examination score was 15/30, and his frontal assessment battery score was 5/18. The findings from routine blood tests including blood sugar and autoimmune antibodies were normal. A laboratory examination showed slightly increased serum pyruvic acid levels (1.2 mg/dL), but his serum lactate levels were normal (14.2 mg/dL). The cerebrospinal fluid lactate (34.8 mg/dL) and pyruvic acid (1.6 mg/dL) levels were elevated. Electrocardiogram and echocardiogram were normal. Brain magnetic resonance imaging (MRI) showed bilateral cortical and subcortical high-intensity lesions on T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion-weighted imaging (DWI) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient (ADC) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H-MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ). 99m Tc-Ethylcysteinate dimer single photon emission computed tomography (SPECT) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions ( Fig. 1E ). We suspected mitochondrial encephalopathy, such as MELAS. A histopathological study of the biopsied right biceps branchii muscle revealed mild variation in the fiber size, measuring from 30 to 90 microns in diameter, which was thought to be a non-specific change. No necrotic or regenerating fibers were seen. On modified Gomori-trichrome stain, ragged red fibers (RRFs) were not observed. Succinate dehydrogenase (SDH) stain revealed no strongly SDH-reactive blood vessels. Cytochrome c oxidase staining revealed no abnormalities ( Fig. 1F ). However, the complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a level of mutant heteroplasmy of 69.5%, in the mitochondrial complex I subunit gene, MT-ND3 ( Fig. 1G ). Because his family had no clinical symptoms suggestive of mitochondrial diseases, we could not conduct a complete mtDNA sequence analysis of his family. Over a two-month period, he experienced two stroke-like episodes with simple partial seizure and vomiting. Each time the stroke-like episodes ended within four days with drip infusion of edaravone and supportive care. To control epileptic seizure, we added levetiracetam (1,000 mg/day) to zonisamide (400 mg/day) and carbamazepine (400 mg/day). Because he had not yet been diagnosed with MELAS-like encephalopathy at that time, we did not administer L-arginine. His higher brain dysfunction and myoclonus worsened with each stroke-like episode.'}", "questions": ["Which gastrointestinal symptom did the patient experience during his hospital admission?"], "ground_truth_arguments": ["vomiting"]}
{"id": "CaseReportBench:train-286", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case report': 'The patient presented at age seven years with intermittent vomiting, diarrhea, constipation, weight loss and fatigue that has persisted for over 18 months. Routine work-up showed significant metabolic acidosis with low serum bicarbonate concentrations. He was started on oral sodium citrate and admitted for evaluation, which revealed low serum glucose of 3.05 mmol/L (55 mg/dL) and very low plasma l -carnitine (total carnitine:7 μmol/L, reference range: 25–69). Serum creatine phosphokinase (CK) and transaminases were elevated and continued to increase as he clinically deteriorated, with CK peaking at 202 μkat/L (12,086 U/L), AST at 341 U/L and ALT at 190 U/L. Ophthalmologic and audiologic exams were normal. Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation disorders. The patient had started on carnitine and cornstarch but continued to deteriorate, with multiple admissions for ketotic hypoglycemia and severe lactic acidosis. Brain magnetic resonance imaging was normal, while brain magnetic resonance spectroscopy (MRS) showed lactate peaks in the left basal ganglion and lateral ventricle. As this finding was suggestive of a mitochondrial disorder, treatment with coenzyme Q10, riboflavin, creatine monohydrate, alpha-lipoic acid, and medium chain triglyceride (MCT) oil was initiated, while continuing carnitine supplementation. Leucovorin was later added due to a low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate level. At age eight, he required a gastric feeding tube (G-tube) placement for malnutrition and continued weight loss. The urine organic acid profile was notable for elevations of lactate, ethylmalonate, 3-methylglutaconate, and branched-chain ketoacids, suggestive of mitochondrial dysfunction. Cultured skin fibroblast testing was performed for suspected defects in fatty acid oxidation, pyruvate carboxylase (EC 6.4.1.1), and pyruvate dehydrogenase complex (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4) with normal results . Analysis of acylcarnitines in cultured skin fibroblasts incubated with palmitic acid and l -carnitine (in vitro probe assay) showed marked elevations of long-chain species, suggestive of carnitine palmitoyltransferase II or carnitine–acylcarnitine translocase deficiency. CSF analysis showed mild elevation of lactate of 3.1 mmol/L (< 2.8), and a low normal level of 5-methyltetrahydrofolate. Transaminitis was initially attributed to a possible GSD; glycogen content was elevated in both liver (10%; control range 3.3 +/− 1.7%) and muscle (3.0%; control range 0.94 +/− 0.55). However, sequencing of PHKA1 and PHKG2 genes (GSD IX) and AGL gene (GSD III) was normal. Activities of debranching enzyme (EC 2.4.1.25 GSD III) and hepatic phosphorylase kinase (GSD IX, EC 2.7.11.19) in the liver and muscle, and glucose-6-phosphatase (GSD Ia, EC 3.1.3.9) in the liver were also normal. Further evaluation for a suspected mitochondrial disorder revealed normal electron transporter chain (ETC) activity in cultured skin fibroblasts. Muscle histopathology demonstrated prominent granular red staining of the fibers with a trichrome stain and numerous mitochondria aggregates by electron microscopy, characteristic of a mitochondrial myopathy ( Fig. 1 ). ETC testing on frozen muscle revealed deficient complex III activity of 455 (mean 1461, standard deviation 473); mtDNA sequencing of the muscle sample revealed a 9 basepair deletion with loss of 3 amino acids Leu-Ala-Thr (m.15319_15327delCCTAGCAAC; p.Leu192_Thr194del, Fig. 2 ) in the MT-CYB gene encoding cytochrome b subunit of complex III, with > 90% mutant load, confirming complex III deficiency. MtDNA sequencing in the liver and blood did not reveal the mutation, although low heteroplasmy for the mutation was detected in uncultured skin fibroblasts. Since the diagnosis, ongoing cardiac evaluations to monitor for cardiomyopathy or rhythm disturbance have been normal. The child dramatically improved with the start of G-tube feeding and dietary supplements, with increased energy level, improved exercise tolerance and progress in academic performance. Previously confined to a wheel chair, he started to walk independently and actively. Lactic acid, transaminases and CK levels have stabilized, although lactate showed occasional elevations as high as 11 mmol/L without symptoms of metabolic decompensation. His G-tube was removed at age 12 years and he stopped taking supplements, and he continues to do remarkably well physically.'}", "questions": ["What were the findings of the ophthalmologic and audiologic examinations?"], "ground_truth_arguments": ["Ophthalmologic and audiologic exams were normal."]}
{"id": "CaseReportBench:train-83", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': \"An eleven month old female child, born of a primigravida mother of non-consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal. There was no similar illness in the family. Her pulse rate was 102/min, blood pressure was 84/58 mm of Hg. and respiratory rate was 25/min. Her weight was 7.9 kg, length was 70 cm and head circumference was 45 cm. There was some pallor. Blisters were present on scalp, face, upper and lower limbs with atrophic scars on scalp and upper limbs along with alopecia. Copper-red discoloration of the two erupted teeth was noted. There was no hepatosplenomegaly. Neurological examination was normal. On the basis of infancy-onset blistering over sun-exposed areas, atrophic scars, red colored urine and teeth without neurological involvement and evidence of arthritis, we reached the provisional diagnosis of CEP. Complete blood count showed mild anemia; Hb-9.2 mg/dl, total leucocyte count-8,200 and platelet count of 1.4 lac/cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2% of circulating erythrocytes (normal upto 2%). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol/mmol of creatinine (normal < 35 nmol/mmol). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method (normal value < 40 mcg/100 ml). Bright red fluorescence was also noted in the urine, teeth and blood under wood's lamp. So, a final diagnosis of congenital erythropoietic porphyria was made. Demonstration of deficiency of UROS activity and genetic study could not be performed due to lack of laboratory facilities.\"}", "questions": ["Were there any notable abnormalities in the complete blood count, such as hemoglobin, leukocyte, or platelet findings?", "What key morphological features were reported on the peripheral blood smear, including red cell size, color, and reticulocyte findings?", "What were the results of the liver and renal function tests?", "What was the result of the HIV ELISA test?", "What were the findings for urinary porphobilinogen?", "Did the spectrophotometric analysis show an abnormal urinary total porphyrin concentration compared to the normal reference range?", "Were the 24‑hour urinary and fecal uroporphyrin and coproporphyrin levels reported as elevated?", "What did the haematofluorometric method reveal about erythrocyte porphyrin concentration relative to normal values?"], "ground_truth_arguments": ["Complete blood count showed mild anemia; Hb-9.2 mg / dl, total leucocyte count-8,200 and platelet count of 1.4 lac / cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2 % of circulating erythrocytes ( normal upto 2 % ). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol / mmol of creatinine ( normal < 35 nmol / mmol ). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method ( normal value < 40 mcg/100 ml )."]}
{"id": "CaseReportBench:train-291", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["When were the hyperpigmented skin lesions first noted in the patient?"], "ground_truth_arguments": ["birth"]}
{"id": "CaseReportBench:train-274", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["What diagnosis was ultimately reached for the patient after the ACTH stimulation test and further genetic and hormonal investigations?", "Which condition was identified as the cause of the patient's virilization and elevated testosterone levels?"], "ground_truth_arguments": ["the diagnosis of NCAH was reached"]}
{"id": "CaseReportBench:train-572", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case presentation': \"An 11-month-old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full-term by Cesarean section and was the second child of the nonconsanguineous parents. The patient's older sibling was phenotypically female, but died in infancy without a clear diagnosis. Although the karyotype was 46, XY, the patient was raised as female gender since she had female external genitalia. In addition, hyponatremia and an elevated adrenocorticotropic hormone (ACTH) level were detected by tests. The blood pressure at clinic was 80/50 mm Hg. Laboratory analysis revealed that the baby had a mildly elevated cholesterol level of 5.72 mmol/L (normal: 2.85–5.70 mmol/L), but a normal triglyceride level. Her plasma sodium level was 131.7 mmol/L (normal: 135–145 mmol/L) with potassium concentration of 6.61 mmol/L (normal: 3.5–5.5 mmol/L). ACTH was >1250 pg/mL (0–46 pg/mL) with a morning cortisol of 1.23 μg/dL (normal: 4–22 μg/dL). Baseline sex hormone tests revealed luteinizing hormone <0.10 U/L, follicle stimulating hormone 1.78 U/L, testosterone 2.50 ng/dL, progesterone 0.44 ng/dL, estradiol 22.99 pg/mL, and dehydroepiandrosterone (DHEA) sulfate <0.1 μg/dL. Adrenal computed tomography (CT) scan revealed enlarged adrenal glands. Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular-like tissues were detected in the bilateral inguinal regions (left: 0.6 × 0.4 cm; right: 0.7 × 0.4 cm) by ultrasonography. Plasma renin activity (PRA) was 0.11 ng/mL per h (normal: 0.93–6.56 ng/mL per h) with a normal aldosterone level of 8.84 ng/dL (normal: 6.5–29.6 ng/dL). Given ambiguous genitalia, karyotype of 46, XY and decreased DHEA and testosterone levels, the diagnosis of 21-hydroxylase deficiency and 11 beta hydroxylase deficiency were excluded. Lacking hypertension and hypopotassemia, the clinical presentation of salt loss and decreased progesterone also did not support the diagnosis of 17OHD. Without an elevated progesterone level, cytochrome PORD was less considered. The differential diagnosis included 3β-HSD deficiency and LCAH. After the informed consent form was signed by the families and approved by the Institutional Review Board of Peking Union Medical College Hospital, further genetic analysis with gene sequencing indicated it is not defective HSD3B2 (related to 3β-HSD deficiency). However, a homozygous variant c.707_708delins CTT (p.Lys236Thrfs∗47) was found on exon 6 of the STAR gene. A truncated disease-causing protein was predicted with MutationTaster software. The variant mutation was found to cause a frameshift at codon 236 with a stop at codon 282. Both parents were found to be heterozygous for the variant (c.707_708delins CTT, p.Lys236Thrfs∗47) at the same locus of the STAR gene without phenotypic consequences. To further evaluate the family pedigree for mutation carriers, the patient's paternal and maternal grandparents also took part in the gene sequencing. The patient's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes (such as mild amenorrhea in women) were recorded, and there were no abnormalities in physical and laboratory examinations. The results of the patient, her parents, and paternal grandfather and maternal grandmother are shown in Fig. 1 . The genogram of LCAH in this family is presented in Fig. 2 . The patient was prescribed hydrocortisone 10 to 12 mg/m 2 and 9α-fludrocortisone 100 μg/d. Gradually, her skin hyperpigmentation and vomiting disappeared, and she had normal growth and development without adrenal crisis attacks. Her hormone and electrolyte levels remained normal, except for a persistently elevated ACTH level throughout 2 years of follow-up. At follow-up for 2 years, the patient is now 104.5 cm tall and weighs 23.3 kg at the age of 4 years old. Her plasma sodium level is 138 mmol/L with a normal potassium concentration of 4.8 mmol/L. Her ACTH level is still elevated (1176 pg/mL). Her baseline sex hormone levels are testosterone <0.1 ng/dL and progesterone <0.08 ng/dL. The level of PRA (1.06 ng/mL per h) is within normal range.\", 'Patient concerns:': 'A case was reported that an 11-month-old Chinese girl who presented with a sex development disorder and hyponatremia. The clinical and genetic tests were carried out to confirm the diagnosis. The genogram of this case was also explored and analyzed. The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular-like tissue in the bilateral inguinal regions were detected with abdominal ultrasound. She was suspected of having LCAH, and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT (p.Lys236Thrfs∗47) on exon 6 of the STAR gene.'}", "questions": ["What gastrointestinal symptom did the patient present with?"], "ground_truth_arguments": ["vomiting", "vomiting"]}
{"id": "CaseReportBench:train-546", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}", "questions": ["What gastrointestinal symptoms, including bowel movement patterns, were reported in the patients during childhood or early life?", "How were the patients' early bowel habits described (e.g., frequency, consistency, regularity) and at what ages did they begin?"], "ground_truth_arguments": ["irregular bowel movements", "loose stools", "early onset of frequent diarrhea"]}
{"id": "CaseReportBench:train-427", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Radiological findings': 'Ultrasonographic examination revealed small hypoplastic uterus (6*7*3 ml) or atretic ovaries and adrenal glands had normal sizes. Clinical Course and Follow-up First, the patient hydrated with normal saline. Thereafter, considering hyponatremia, hyperkalemia, metabolic acidosis and decreased cortisol level and increased ACTH level, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) and sodium chloride was initiated. After replacement therapy, electrolyte abnormalities were corrected during first week and the patient was discharged from hospital with good clinical condition. She recommended referring for follow up. During follow-up, she had good clinical condition, with normal laboratory results except for 17 OHP which was lower during the period. At 6-years old, the patient referred with high blood pressure and adrenal insufficiency because of arbitrary drug discontinuation by mother. Renal Doppler ultrasonography and scan was performed which was normal. Regarding the recommendation of pediatric nephrologist fludrocortisone and sodium chloride was discontinued and treatment continued with hydrocortisone . Ultrasonography revealed the testicles in the abdominal cavity and uterus was not detected in pelvis. Orchiectomy was performed. Chromosome study showed 46XY pattern. On her most recent visit at the age of 6 years, the patient had no hyperpigmentation. Her height was 110 cm (10-25th percentile), weight 23 kg (75-90th percentile). Her last laboratory tests results were as follows; Na: 142 mmol/l, K: 4.5 mmol/l,17OHP: 0.1 ng/ml, ACTH: 22 pg/ml, Renin:50.8 pg/ml, Aldosterone: 105 pg/ml.', 'CASE REPORT': 'A 28-day-old phenotypic female infant was admitted to pediatric endocrinology clinic of Al-Zahra Hospital, affiliated to Isfahan University of Medical Sciences, because of poor weight gain and lethargy. She was a full-term infant with a birth weight of 3250 gr (50 th percentile), length of 51 cm (50 th percentile) and head circumference of 34 cm (50 th percentile).The patient had no perinatal problem. She was the 1 st child of nonconsanguineous parents. At the time of admission, she was lethargic without history of vomiting or diarrhea. There was not any familial history of similar presentation or features endocrine disease. She had no history of drug consumption except vitamin A+D.', 'Physical examination': 'She was lethargic, had depressed fontanele. She had mild dehydration and decreased skin turgor. In skin examination, she had mild hyperpigmentation, including oral cavity. External genitalia seemed normal female type with no ambiguity. There was not any abdominal or inguinal mass in abdominal examination. Her body weight, length and head circumference were 2900, 51 cm and 33.5 cm, all of them were beneath the 5 th percentiles. Her blood pressure was 60/40 mmHg, respiratory rate was 39/min, pulse rate was 112/min and body temperature was 37.1°C.'}", "questions": ["What was the gestational age at birth and were any perinatal complications reported?", "Were the infant's birth anthropometric measurements (such as weight, length, and head circumference) within normal ranges for gestational age?"], "ground_truth_arguments": ["full - term infant with a birth weight of 3250 gr ( 50 th percentile ), length of 51 cm ( 50 th percentile ) and head circumference of 34 cm ( 50 th percentile).The patient had no perinatal problem."]}
{"id": "CaseReportBench:train-305", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case Report': 'We report on a 5-year-old girl with a history of pink-stained urine as a newborn. Disease onset occurred in the tenth month of life. Her deciduous teeth sprouted with a red-brown color. She also suffered from episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation (fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas. Spleen enlargement was also observed. Urine porphyrins were extremely elevated to 16 μmol/dl with a predominance of coproporphyrins and uroporphyrins. However, the detailed concentration of each porphyrin was not analyzed. Severe cutaneous photosensitivity, blistering of light-exposed skin, history of pink-stained diapers and accumulation of porphyrins in the blood and various other tissues, particularly erythrodontia (fig. 1b ), suggested the diagnosis of CEP. The clinical and biochemical data of the patient are summarized in table 1 . With strict avoidance of UV and visible light, use of topical sunscreen, oral treatment with β-carotene and antibiotic for preventing bacterial infection of the skin, the bullae healed, leaving milia and hyperpigmented scars without the need of a blood transfusion. Mutation analysis of the UROS gene of the patient with CEP was performed. The DNA of exons 2–10 including splicing junctions of all exons was amplified by PCR and then sequenced. A single missense mutation corresponding to a G-to-T transversion (11,776 g>t) in exon 2 was found, leading to an amino acid change from valine at position 3 to phenylalanine (fig. 2 ). The result indicated that the patient was homozygous for this mutation. Then, we also analyzed the UROS genes of her parents who were shown to be heterozygote carriers of this mutation (fig. 3 ). Her brother had died of a disease similar to hers in terms of symptoms and abnormalities, suggesting that he had the same gene mutation (V3F). Conversely, on the basis of the pedigree analysis spanning three generations, no other symptomatic patients were found. To confirm the genotype-phenotype relationship, we constructed a pET-duet vector carrying mutated cDNA of UROS and transformed it into an Escherichia coli BL21 strain. The expression of UROS in bacteria was induced at 25°C. After purification of the expressed enzyme with nickel ion-beads (Qiagen Inc., Valencia, Calif., USA), the activity of mutated UROS (V3F) was compared with that of normal enzyme by the method of Wright and Lim. The specific activity of the mutated UROS was less than 16.1% that of the control.'}", "questions": ["What measures were taken to limit the patient's exposure to ultraviolet and visible light?", "What topical agents were applied to protect the patient's skin from light exposure?"], "ground_truth_arguments": ["strict avoidance of UV and visible light , use of topical sunscreen ,"]}
{"id": "CaseReportBench:train-217", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': 'We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. The Saudi female patient in the UK developed recurrent bouts of abdominal pain, nausea, and vomiting during first pregnancy, diagnosed as hyperemesis gravidarum, and was treated with IV fluids and antiemetics. There was improvement in the condition and the patient delivered a healthy child (in Saudi). After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatremia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities. She was intubated for 3 days. Initial postextubation, physical examination result was unremarkable except for unexplained behavioral disturbances and lower limb weakness. Initial instigations showed sodium levels ranged between 118–125 mmol/L (135–144 mmol/L), mildly elevated transaminases (aspartate aminotransferase/alanine transaminase), and slight elevation of anti-neutrophil antibodies of the perinuclear type (P-ANCA). Alkaline phosphatase, bilirubin, complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid (CSF) analysis findings were all within normal range. The abdominal imaging result was normal, except for contracted gallbladder and stones. Urine became dark red on exposure to light. Total porphyrins in urine were elevated: 29,100 nmol/24 hours (normal: ≤214), with main elevation in uroporphyrin level, 24,200 nmol/24 hours (normal: ≤30), and mild elevation in coproporphyrin level, 118 nmol/24 hours (normal: ≤38). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene (c. 760delC p.L254X). The patient was treated with intravenous heme arginate (4 mg/kg/day) for 5 days, that was followed by an improvement in the chemical and clinical parameters.'}", "questions": ["What is the confirmed diagnosis of the patient described in the case report?", "What diagnostic criteria were applied to determine the porphyria subtype in this patient?", "What genetic mutation in the HMBS gene was found that confirms the diagnosis?"], "ground_truth_arguments": ["AIP"]}
{"id": "CaseReportBench:train-168", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Patient 2': 'The elder sister of patient 1 was an 84-year-old woman with a stooping posture presenting with tremors since the age of 60. In her 70s she started walking with the aid of a walking stick. At 82 years of age, she was hospitalized for generalized seizures and disturbed consciousness. CT of T10 revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 e). Brain MRI revealed hyperintense lesions around the white matter (Fig. 2 f); elevated serum and CSF lactate levels were also noted at this time. The mitochondrial DNA analysis of the lymphocytes did not indicate MELAS (m.3243A>G) or MERRF (m.8344A>G) mutations. The patient’s condition remained undiagnosed and she died at the age of 84. CK levels in all her four sons were found to be elevated and her third son was diagnosed with epilepsy. She and her fourth son had also been previously diagnosed with Hashimoto thyroiditis (Fig. 1 ). Patient 1 was examined using pathological, biochemical, and genetic analyses. The Institutional Review Board of Kagoshima University approved this study. Patient 1 gave the written and informed consent for her participation in this study.', 'Histochemical and immunohistochemical studies': 'Frozen biopsies of the biceps brachii muscle specimens were obtained from patient 1. The specimens were sliced into 8 μm sections and placed on aminosilane-coated slides. Histochemical and immunohistochemical procedures were performed as previously described.', 'Histological and immunohistochemical characterizations': 'The muscle fibers ranged from 10 to 80 μm in diameter. Sixty-nine of the 609 Gomori trichrome stained muscle fibers (11.3%) were ragged-red fibers (Fig. 3 a). Cytochrome c oxidase (COX) activity was deficient in many of the ragged-blue fibers that were stained with succinate dehydrogenase (SDH) and COX (233 of 881 muscle fibers, 26.4%) (Fig. 3 b, c), and no blood vessels showing strong SDH reactivity were observed. In NADH dehydrogenase-reactive sections, focal decreases and increases in oxidative enzyme activities were observed. Adenosine monophosphate (AMP) deaminase activity was normal. The random checkerboard distribution of the histochemical fiber types was preserved as shown in the ATPase-reactive sections. Acid phosphatase activity was slightly high in some fibers. Muscle fiber glycogen contents appeared normal and the lipid contents were slightly high in some fibers. Electron microscopy showed abnormal proliferation of mitochondria with paracrystalline inclusions (Fig. 4 ). Fig. 3 Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged-red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged-blue fibers with COX deficiency. a−c Bar 100 μm Fig. 4 Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions that are suggestive of mitochondrial myopathy are shown. a bar 1 μm, b bar 500 nm', 'Mitochondrial DNA analysis': 'In case of patient 1, the total DNA was extracted from the peripheral blood leukocytes and the frozen muscle specimens using the DNeasy Blood & Tissue kit (Qiagen). MitoChip v2.0 (The GeneChip ® Human Mitochondrial Resequencing Array 2.0), which provides a standard assay for the complete sequence analysis of human mitochondrial DNA, was obtained from Affymetrix. The patient’s entire mitochondrial DNA was sequenced using MitoChip v2.0 as previously described. Analysis of the microarray data obtained with MitoChip v2.0 was performed using GeneChip Sequence Analysis Software v4.0 (Affymetrix). In order to reveal the mutations that were confirmed by MitoChip v2.0, a 465-base pair PCR product that spanned all of the mutation sites was screened by DNA sequencing. In brief, 50 ng of the patient’s genomic DNA was amplified using the hot-start PCR method and a forward (5′-CACCATTCTCCGTGAAATCA-3′) and reverse primer (5′-AGGCTAAGCGTTTTGAGCTG-3′). Each PCR product was generated under the following conditions: 15 min at 95°C, 42 cycles of amplification (95°C for 30 s, 61°C for 30 s, and 72°C for 1 min), and 30 min at 72°C. Using a presequencing kit (USB, Cleveland, OH, USA), the patient’s PCR products with abnormal elution profiles were purified, and the appropriate PCR products from relatives and control chromosomes were obtained and sequenced by dye-terminator chemistry using an ABI Prism 377 sequencer (Applied Biosystems, Foster City, CA, USA). The resulting sequences were then aligned and any mutations were evaluated using the Sequencher sequence alignment program (Gene Codes, Ann Arbor, MI, USA). The polymorphic and pathogenic natures of the confirmed mutations were checked against two databases: the MITOMAP ( http://www.mitomap.org/ ) and GiiB-JST mtSNP database ( http://mtsnp.tmig.or.jp/mtsnp/index.shtml ). Using MitoChip v2.0, 37 missense variants were detected in the mitochondrial DNA of the peripheral blood lymphocytes. All of these variants show polymorphisms and are listed in the MITOMAP and GiiB-JST mtSNP databases. Two additional missense variants were detected in the mitochondrial DNA of the muscle homogenate; the variants were m.602C>T in the tRNA Phe gene and m.16111C>G in the D-loop. The variant m.16111C>G is listed as a polymorphism, but the variant m.602C>T is not reported in either database. The m.602C>T variant was also confirmed by direct sequencing. The sequence chromatogram showed a heteroplasmic m.602C>T transition in the muscle homogenate mitochondrial tRNA Phe gene (Fig. 5 a). The proportion of mutant mitochondrial DNA in the muscle was 64.7 ± 1.2% (mean ± SD; the operation was performed thrice). Mutant mitochondrial DNA was not detected in the blood lymphocytes when measured using real-time amplification refractory mutation system quantitative PCR analysis (RT-ARMS qPCR), as previously described. Healthy Japanese controls ( n = 100) did not show these mutations in their blood lymphocytes, at least not within the limits of Sanger’s method for DNA sequencing. Fig. 5 a Sequence chromatogram of the mitochondrial DNA region that encompasses the m.602C>T alteration ( asterisk ) that was obtained from the skeletal muscle of patient 1 (reverse complement). b Schematic diagram of the mitochondrial tRNA Phe cloverleaf structure showing previously reported mutations and the m.602C>T alteration in the D-stem. c Comparison of mitochondrial tRNA Phe from different species. Base pairs, including the 602 nucleotides, are shown in boxes', 'Patient 1': 'A 73-year-old woman (Fig. 1, III-8) presenting with abnormal posture and gait disturbance. Since the age of 63, the patient had a slight stooping posture and a pushed-out waist. At 68 years of age, she started using a walking stick because of her unstable gait. She was diagnosed with hypothyroidism by her family physician and administrated with 25 μg/day levothyroxine; however, her symptoms did not improve. At 70 years of age, it gradually became more difficult for her to climb the stairs. At 71 years of age, she was admitted to another hospital. Doctors suspected myopathy because of elevated serum CK levels. She visited our hospital presenting with prominent paraspinal muscle atrophy and mild proximal weakness of limbs. Hypothyroidism-related myopathy was suspected in her, and hence, the levothyroxine dose was increased to 50 μg/day; however, her symptoms did not improve. She had a family history of bent spine, i.e., in her elder sister (patient 2, Fig. 1, III-5), mother (Fig. 1, II-3), and maternal aunt (Fig. 1, II-4). Physical examination on arrival revealed a marked atrophy of the paraspinal muscles and abnormal posture (Fig. 2 a, b). She also presented with right ptosis, dysarthria, bilateral cataracts, and hearing loss. Her eye movements were normal. But there was moderate weakness of the neck flexion and mild weakness of the proximal limb muscles. Tendon reflexes were symmetrical, and Babinski’s sign was absent. She had poor balance with tandem gait without limb ataxia. Sensory systems were intact and Romberg’s sign was negative. She scored poorly on the attention and calculation tests that are a part of the Mini-Mental State Examination (score: 25 points). Fig. 1 Pedigree of the family. The arrow indicates the proband. The affected individuals are represented by the solid black symbols ; open symbols represent healthy individuals. Gray symbols indicate individuals with elevated CK levels Fig. 2 a The full-length figure indicates the posture of patient 1 showing her pushed-out waist. b The dorsal view shows the marked atrophy of the paraspinal muscles in patient 1. CT of T10 of c patient 1 (age 71), e patient 2 (age 82), and g a healthy female (age 74) reveals the profound atrophy of the paraspinal muscles in c patient 1 and e patient 2, but not in g the healthy female. Brain MRI studies revealed several differences between the patients 1 and 2. d Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter Laboratory data were as follows: serum CK level was 290 IU/l (normal range 45–163 IU/l), resting blood and cerebrospinal fluid (CSF) lactate levels were normal, thyroid-stimulating hormone levels were slightly low at 0.47 μIU/ml (normal range 0.5–5.0 μIU/ml). Under the administration of 50 μg/day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U/ml (normal range <0.3 U/ml), antithyroid peroxidase antibody levels were high at 46.5 U/ml (normal range <0.3 U/ml), rheumatoid factor levels were high at 152.3 IU/ml (normal value <15.0 IU/ml), antinuclear antibody levels were mildly elevated (titer of 1:80). Autoimmune analyses, including anti-Jo-1, anti-RNP, anti-SS-A, and anti-SS-B, were negative. The oral glucose tolerance test (75 g) was within normal limits, but Holter monitoring revealed high-frequency premature contractions. Pure-tone audiometry indicated sensorineural and high-frequency hearing loss. Needle electromyographic findings of the biceps brachii and rectus femoris muscles indicated mild myopathic features. Computed tomography (CT) of the thoracic spinal nerve 10 (T10) revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 c). Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery imaging showed moderate cerebellar and temporo-parieto-occipital lobe atrophy (Fig. 2 d). MR spectroscopy revealed the absence of increased lactate peaks. 123I-IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions.', 'Biochemical studies': 'Enzyme activity levels, blue native polyacrylamide gel electrophoresis (BN-PAGE), and other biochemical measurements of the frozen muscle specimens from patient 1 were performed as previously described. All respiratory chain enzyme activities, which are expressed as a percentage of the normal control values relative to the citrate synthase activity, were greater than 20% (Table 1 ). BN-PAGE revealed no abnormalities in either the respiratory chain complexes or their molecular assembly structures. Table 1 Enzymatic activities for mitochondrial respiratory complexes in patient 1 CI activity (CI/CS) CII activity (CII/CS) CIII activity (CIII/CS) CIV activity (CIV/CS) CS activity Patient 1 0.1938 (0.7027) 0.2723 (0.9874) 1.2737 (4.6192) 0.0579 (0.21) 0.2757 Control 0.3194 (1.6183) 0.2751 (1.3444) 1.3132 (6.5512) 0.0826 (0.3840) 0.2151 Patient 1/control ratio 60.7% (43.4%) 98.9% (73.4%) 97.0% (70.5%) 70.1% (54.7%) Enzymatic activities for individual mitochondrial respiratory complexes are given in nmol/min protein, and represent percentage of normal control ( n = 10) mean relative to a reference enzyme of citrate synthase (CS) The activities are relatively low in complex I and complex IV compared with other complexes CI complex I, CII complex II, CIII complex III, CIV complex IV'}", "questions": ["What age is reported for patient 1 at the time she was examined or presented in the study?", "What age is reported for patient 2 at the time she was examined or presented in the study?"], "ground_truth_arguments": ["84 - year - old", "73 - year - old"]}
{"id": "CaseReportBench:train-362", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE': 'A 56-year-old man, who had been a heavy drinker, presented symptoms of general weakness, abdominal discomfort, diarrhea and weight loss and was admitted to the hospital. On examination, he was found to be cachectic and his abdomen slightly distended with shifting dullness. Laboratory examination revealed a hemoglobin level of 13.1 g/dL; white blood cell count, 17,800/mm 3 ; platelet count, 553,000/mm 3 ; albumin, 2.6 g/dL; total bilirubin, 0.3 mg/dL; GOT, 48 IU/L; GPT, 22 IU/L; and alkaline phosphatase, 117 IU/L. His serum amylase was 856 IU/L and serum lipase 1,077 IU/L. A computed tomographic (CT) scan of the abdomen ( Figure 1 ) revealed evidence of acute exacerbated, chronic pancreatitis, including pseudocysts, one of which was approximately 7 cm in diameter and was located in the tail of the pancreas with adjacent splenic vein occlusion. In addition, right portal vein occlusion, with corresponding perfusion defect and liver infarction, was noted. The patient was treated initially with intravenous fluids, antibiotics and TPN. Two weeks after treatment including TPN, the patient exhibited multiple skin lesions and continued to experience diarrhea more than 10 times daily. These skin lesions were vesiculopustular and erythematous eruptions with scales on the face ( Figure 2A ) and perineal areas. During the following week, the lesions spread to involve the hands and feet ( Figure 2B, 2C ). He became depressed and agitated. In view of typical skin lesions, mental change and protracted diarrhea, we strongly suspected acrodermatitis enteropathica due to zinc deficiency. His serum zinc level was found to have fallen to 17.4 μ g/dL (normal range, 70 to 150 μ g/dL) and, therefore, we initiated therapy with zinc sulfate at 5 mg daily. Three to four days of zinc supplementation produced marked improvement of the diarrhea and, after one week of zinc supplementation, the skin lesions began to alleviate. The patient continued to do well until five weeks after TPN when abdominal pain and fever developed. With strong suspicions of an infected pancreatic pseudocyst, we performed an abdominal CT scan and subsequently a percutaneous pigtail insertion to drain the pseudocyst. Soon thereafter, he felt well with no pain or fever. A repeat CT scan 10 days later showed total collapse of the pseudocyst and resolution of the PVT and liver infarction. On the 74th hospital day, he was discharged without any problem. By this time, his skin lesions had almost healed.'}", "questions": ["Which laboratory test results were highlighted in the report?", "What key findings were described on the initial abdominal CT scan?", "How was the patient's serum zinc status described in the report?", "What changes were noted on the repeat CT scan performed ten days after pseudocyst drainage?"], "ground_truth_arguments": ["Laboratory examination revealed a hemoglobin level of 13.1 g / dL; white blood cell count, 17,800 / mm 3; platelet count, 553,000 / mm 3; albumin, 2.6 g / dL; total bilirubin, 0.3 mg / dL; GOT, 48 IU / L; GPT, 22 IU / L; and alkaline phosphatase, 117 IU / L. His serum amylase was 856 IU / L and serum lipase 1,077 IU / L.", "computed tomographic ( CT ) scan of the abdomen ( Figure 1 ) revealed evidence of acute exacerbated, chronic pancreatitis, including pseudocysts, one of which was approximately 7 cm in diameter and was located in the tail of the pancreas with adjacent splenic vein occlusion. In addition, right portal vein occlusion, with corresponding perfusion defect and liver infarction, was noted", "His serum zinc level was found to have fallen to 17.4 μ g / dL ( normal range, 70 to 150 μ g / dL )", "A repeat CT scan 10 days later showed total collapse of the pseudocyst and resolution of the PVT and liver infarction"]}
{"id": "CaseReportBench:train-530", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case 2': 'This patient too showed considerable hyperkeratosis of palms and soles. Intraoral examination showed more teeth present. Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds. All teeth had deep periodontal pockets and grade II mobility. Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits. On the basis of history, clinical and radiographical features a diagnosis of Papillon-Lefevre syndrome was made.', 'CASE REPORT': 'An 18-year-old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi-Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16-year-old brother also complained of similar problems. Systemic history-both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2-3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.', 'Case 1': 'Patient showed bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees. Intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility. Orthopantomograph showed severe horizontal bone loss..'}", "questions": ["How many teeth are reported as present in the intraoral examination?", "What degree of tooth mobility is described, and is bleeding of the gums mentioned?", "What proportion of permanent teeth are reported as lost, and what mobility grade is noted for the remaining teeth?"], "ground_truth_arguments": ["more teeth present", "generalized mobility of teeth and bleeding gums.", "patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility."]}
{"id": "CaseReportBench:train-559", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'CASE REPORT': 'We present the case of a 28‐year‐old Mexican woman who came to our clinic because she had been experiencing recurring episodes of intense abdominal pain, weakness in her upper and lower extremities, uncontrollable vomiting, and insomnia since the age of 17. These symptoms required frequent visits to the emergency department. Despite undergoing normal biochemical and imaging tests, not responding to pain relief medications, and even undergoing abdominal surgery for suspected acute appendicitis, her symptoms persisted. After enduring nearly 3 years of almost daily symptoms, an episode of elevated urine PBG during a crisis finally confirmed the diagnosis of AIP. Treatment with hematin derivatives (Normosang®, Panhematin®) was initiated, resulting in partial improvement. However, subsequent years witnessed progressively severe crises, some accompanied by paralysis and kidney injury. Remarkably, elevated urine PBG was even detected during asymptomatic periods. Notably, her first cousin was also diagnosed with AIP and had a similar clinical presentation. A molecular genetic study was conducted at a reference center in Belgium. All coding exons (1, 3–15), including parts of the adjacent intronic sequences and regions of the 5′‐ and 3´‐UTR of the HMBS gene, were PCR‐amplified from genomic DNA. The amplicons underwent direct sequencing using capillary electrophoresis and the BigDye technology (Applied Biosystems). Data alignment and comparison with the wildtype sequence (NM_000190.3) were performed using the GenBank Database. This analysis revealed a heterozygous state mutation, c.457C > T (p.Q153, exon 9, HMBS gene). At the age of 38, she enrolled in a clinical trial for Givosiran, an RNA interference therapeutic targeting ALAS1 mRNA. Remarkably, she exhibited a notable response to the treatment and continued it even after the trial. Over the past years, her symptoms have been sporadic, and she has not required hospitalization. The patient is now 42 years old.'}", "questions": ["Which body regions were reported to have weakness in the patient?"], "ground_truth_arguments": ["weakness in her upper and lower extremities"]}
{"id": "CaseReportBench:train-596", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["What were the maternal serum screening findings for estriol, AFP, and hCG?", "What fetal karyotype was reported from the amniocentesis?", "What findings did the Level II ultrasound after 21 weeks' gestation show regarding structural abnormalities, specifically of the adrenal glands and genitalia?", "Which homozygous mutation in exon 7 was identified, and what amino‑acid change did it result in?", "What did the newborn's screening for congenital adrenal hyperplasia reveal?", "How did the laboratory profile of the second baby compare to her sister's, and what did the adrenal gland ultrasonography reveal?", "What did genetic evaluation of the peripheral blood confirm about the presence of the mutation?"], "ground_truth_arguments": ["Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median ( MoM ) with low alpha - fetoprotein ( AFP ) and human chorionic gonadotropin ( hCG ) level, 0.6 MoM and 0.52 MoM, respectively", "karyotype by amniocentesis was 46,XX", "Level II ultrasonography after 21 weeks ' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia", "homozygous c.772C > T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 )", "Screening for congenital adrenal hyperplasia was normal, 17α - OH progesterone ( 17α - OHP ) 8.33 ng / mL ( normal 1.7 - 25.0 ng / mL )", "laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography", "Genetic evaluation from the peripheral blood confirmed the same mutation"]}
{"id": "CaseReportBench:train-324", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case report': \"The patient was a 37-year-old female, of 157 cm in height and 45 kg in weight. She was transferred to our department from a local hospital due to psychiatric features (both agitated behavior and auditory hallucinations), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic-clonic seizures. She had a long history of episodic migraine-like headaches and progressive bilateral hearing loss for 3 years. However, she did not take any medication. Her vital signs showed a normal body temperature of 36.8 °C, a hypotension of 90/56 mm Hg and pulse at 72 beats per minute. Because of the patient's psychiatric symptoms and application of sedative after seizure attacks, she could not cooperate with physical examination. The laboratory data showed high anion gap metabolic acidosis with elevated levels of lactate and pyruvate. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were decreased. Her TSH level was low at 0.26 mU/L (normal range 0.35–5.5 mU/L), and FT4 concentration was 7.56 pmol/L (normal range 10.2–31 pmol/L). Both serum free and total triiodothyronine (FT3 and TT3) were significantly lower than normal range. FT3 concentration was 2.28 pmol/L (normal range 3.5–6.5 pmol/L), and TT3 concentration was 0.6 nmol/L (normal range 1.2–3.4 nmol/L). Moreover, elevated titers of serum anti-thyroglobulin and anti-thyroid microsomal antibodies were detected. Cerebral spinal fluid (CSF) studies were normal for cell counts and biochemistry, and negative for culture. CSF IgG index was 0.48 (normal range ≤ 0.7), and oligoclonal bands (OB) was negative. Computed tomography (CT) scan showed lesions of hypodense in the left temporal and parietal lobe, with brainstem and cerebellar atrophy ( Fig. 1 A). No evidence of subarachnoid or intracerebral hemorrhage. Vascular imaging of the cervical and cerebral arteries by CT angiography excluded the possibility of cerebrovascular disease ( Fig. 1 B). However, CT images were not conclusive to differentiate between the infectious or metabolic lesion. On day 5, brain magnetic resonance imaging MRI (3.0 T) revealed a hypointensity lesion in the left temporal-parietal lobe on T1 weighted image ( Fig. 2 A), and increased signal intensity in the same region on FLAIR sequences ( Fig. 2 B) with a clearly restricted diffusion ( Fig. 2 C). The signal intensity on ADC sequence was mildly reduced ( Fig. 2 D). No obvious enhancement was found on Gd-DTPA enhanced images ( Fig. 2 E). MR spectroscopy was carried out as well. Compared to the ipsilateral normally appearing area ( Fig. 2 F), there was a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) with decreased NAA spectrum and reduced NAA/Cr ratio ( Fig. 2 G). The change of the spectrum reflected the severity of metabolic disorders, suggesting the local accumulation of lactic acid and disturbance of hypoxic processes. Fig. 1 CT scan showed lesions of hypodense in the left temporal and parietal lobe (Panel A). Three-dimensional reconstruction of CT vessel images (Panel B). Fig. 1 Fig. 2 Brain MRI (3.0 T) revealed a hypointense lesion in the left temporal and parietal lobe on T1 (Panel A), and increased signal intensity in the same region on Flair (Panel A) image with a clearly restricted diffusion (Panel C). The signal intensity on ADC sequence is mildly reduced (Panel D). No obvious enhancement was found on Gd-DTPA enhanced images (Panel E). Compared to the ipsilateral normally appearing area (Panel F), MR spectroscopy presented a significantly elevated lactate peak at 1.3 ppm in region of interest (ROI) (Panel G). Panels f and g are the molecular findings of metabolites respectively. Fig. 2 An electroencephalogram was performed on day 7 and displayed bilateral slow wave activities. Brainstem auditory evoked potential (BAEP) showed the bilateral sensorineural hearing loss. All the clinical and radiological findings were suggestive of mitochondrial disease. The final diagnosis of MELAS syndrome was confirmed by genetic analysis. The patient's peripheral blood leukocytes was detected by restriction fragment length polymorphism (RFLP) and revealed a mitochondrial DNA (mtDNA) mutation at A3242G point ( Fig. 3 ). Fig. 3 Mitochondrial DNA (mtDNA) mutation at A3242G point. Fig. 3 Her medications included L-arginine, phenobarbital, co-enzyme Q and levothyroxine substitution therapy. The patient's condition continuously improved, and was discharged on day 23. Six months following discharge, this patient had no further seizure.\"}", "questions": ["What neuropsychiatric manifestations did the patient exhibit early in the course, and what was the approximate timing of their onset?", "What subsequent neurological changes occurred after the initial presentation?", "What is the patient’s past history regarding episodic migraine‑like headaches?", "What findings were observed on the electroencephalogram performed early in the hospitalization?"], "ground_truth_arguments": ["psychiatric features ( both agitated behavior and auditory hallucinations ), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic - clonic seizures. She had a long history of episodic migraine - like headaches", "An electroencephalogram was performed on day 7 and displayed bilateral slow wave activities."]}
{"id": "CaseReportBench:train-275", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case': \"A 36 years man presented with severe obstructive LUTS. On digital rectal examination prostate was hard and nodular. Flow was a Q max of 2 mL/s for a voided volume of 130 mL and post void residual urine volume of 380 mL. Prostate specific antigen (PSA) was 0.393 ng/mL, while X-ray of pelvis showed punctate calcification in the region of pubic symphysis ( Fig. 1 ), computerized tomography scan of pelvis showed extensive and well calcified areas into the prostatic parenchyma ( Fig. 2 ). On further evaluation, he gave history of passage of dark colored urine and chronic low back ache. He was short statured with kyphotic spine. Osler's sign (bluish discolouration of sclera) was present ( Fig. 3 ). Biochemical analysis of urine showed the presence of homogentisic acid. These findings confirmed the diagnosis of alkaptonuria. He underwent transurethtral clearance of prostatic calculi which revealed multiple blackish calculi in prostatic urethra and in prostatic fossa ( Fig. 4 ) and clearance of calculi. On biochemical analysis, calculi were composed of calcium oxalate and uric acid. Figure 1 Punctate calcification in the region of pubic symphysis by X-ray of pelvis. Figure 2 Extensive prostatic calcification by computerized tomography. Figure 3 Osler's sign. Figure 4 Cystoscopic view of prostatic urethra contaning calculi and postprocedure extracted calculi.\"}", "questions": ["What back-related symptoms were reported by the patient?", "What observations regarding the patient's stature and spinal curvature were documented?"], "ground_truth_arguments": ["chronic low back ache. He was short statured with kyphotic spine"]}
{"id": "CaseReportBench:train-354", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}", "questions": ["What abnormalities, if any, were identified on the carotid artery ultrasound?", "What were the findings on electrocardiogram, echocardiography, and MR angiography regarding the presence of cardiovascular disease?"], "ground_truth_arguments": ["Ultrasound of the carotid arteries showed a slightly thickened intima - media complex at the left common carotid artery ( maximum intima - media thickness, 1.2 mm ). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities"]}
{"id": "CaseReportBench:train-513", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Diagnoses:': 'Ultimately, the patient was diagnosed with argininemia with homozygous mutation (c.32T>C) of the ARG1 gene at 10 years old. Blood tests showed mildly elevated blood ammonia and creatine kinase, and persistently elevated bilirubin.', 'Case report': \"The patient was born at 36 +4 weeks’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness. At this time, his height and weight were 86 cm and 12.5 kg, respectively (both were below the 3rd percentile, according to China's 1995 urban 0–18 year-old male height percentiles scale). A neurologic examination focusing on the motor and sensory nervous system and cerebellar function produced unremarkable findings. Laboratory tests revealed retardation of bone age (equivalent to a 1 year old) and mildly elevated total bilirubin (29.4 μmol/L, normal range: 2–24 μmol/L), direct bilirubin (10.4 μmol/L, normal range: 0–7 μmol/L), and indirect bilirubin levels (18.6 μmol/L, normal range: 1.7–17 μmol/L) but normal hepatic enzyme levels. Blood glucose was slightly lower than normal (3.52 mmol/L, normal range: 3.9–6), whereas his electrolytes were normal. Screening tests for hepatitis B and A were negative. A growth hormone excitement test revealed low levels of growth hormone (0 minute: 0.76 ng/mL; 30 minutes: 4.5 ng/mL; 60 minutes: 6.3 ng/mL; 90 minutes: 4.1 ng/mL; and 120 minutes: 1.5 ng/mL). An MRI revealed a normal pituitary gland, and thyroid function was normal. The boy was diagnosed with PGHD and managed accordingly, being treated with growth hormone for about 1 month. No treatment effect was evident. However, he received no follow-up until 10 years of age. At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance. At this time, his height and weight were still below the 3rd percentile, at 116 cm and 20.1 kg, respectively. He exhibited no organomegaly. His muscle strength of the low extremities was grade 4 (Oxford Scale), and he showed increased distal muscle tone than normal, hyper-reflexia, and a negative Babinski sign. Laboratory tests revealed mildly elevated hepatic enzyme levels, including aspartate transaminase (50.9 IU/L, normal range: 0–50 IU/L) and alanine transaminase (52 IU/L, normal range: 0–45 IU/L), as well as mildly elevated total bilirubin (47.7 μmol/L, normal range: 0–25 μmol/L), direct bilirubin (16.4 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (31.3 μmol/L, normal range: 0–25 μmol/L). His creatine kinase (564.4 IU/L, normal range: 55–190 IU/L) and blood ammonia levels (62.3 mmol/L, normal range: 9–30 mmol/L) were slightly elevated. A urine occult blood test was positive (++). Red blood cells (3–4/HP, normal range: 0–3/HP) were evident in a urine sediment microscopy. Both renal ultrasound and renal function were normal, as were the results of cranial MRI and electroencephalography. A peripheral nerve examination revealed reduced compound muscle action potential (CMAP) of the right peroneal nerve and bilateral tibial nerve, while the right peroneal nerve distal latency was suspected to be prolonged. A muscle biopsy revealed neurogenic lesion (Fig. 1 ). A gene test was performed and the results demonstrated that he carried compound homozygote mutations of ARG1 (c.32T > C) (Fig. 2 ). Lee et al and Wu et al reported the mutation, which can lead to argininemia, in South Korea and Chinese populations in 2011 and 2015. Subsequently, his blood and urine amino acid levels were analyzed, revealing a blood arginine concentration of 108.42 μM (normal range: 10–50 μM) as well as elevated urinary excretion of orotic acid; however, his blood citrulline, glutamine, glutamate, and alanine concentrations were normal. His intelligence quotient was lower than normal, at 80. The boy subsequently diagnosed with argininemia. Following the diagnosis, we recommended that the patient begins a low-protein diet (0.8 g/kg/day) to decrease his blood arginine levels, as well as start taking citrulline (150–200 mg/kg/day). His mental state and vomiting had clearly improved after 3 months of this treatment. Laboratory tests conducted again at a local hospital which the following values were obtained (note that the normal ranges used at this hospital slightly differ from those used at our hospital): aspartate transaminase (45 IU/L, normal range: 0–37 IU/L), alanine transaminase (46.1 IU/L, normal range: 0–40 IU/L), total bilirubin (31.9 μmol/L, normal range: 3.4–20.5 μmol/L), direct bilirubin (14.3 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (17.6 μmol/L, normal range: 0–18 μmol/L). His urine occult blood test was positive (+). No red blood cells were evident in his urine sediment microscopy. After 9 months treatment, his height and weight reached 121 cm and 22 kg, but his spastic diplegia symptoms had not improved.\", 'Patient concerns:': 'A Chinese boy initially presented with severe stunting and partial growth hormone deficiency (PGHD) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later (at 10 years old), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy.'}", "questions": ["At what age did the patient first exhibit symptoms or developmental delays associated with argininemia?"], "ground_truth_arguments": ["1 year of age"]}
{"id": "CaseReportBench:train-497", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}", "questions": ["At what age did the patient first develop recurrent abdominal pain and vomiting?"], "ground_truth_arguments": ["4 years of age"]}
{"id": "CaseReportBench:train-271", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["How is the patient's skin pigmentation described in the report?"], "ground_truth_arguments": ["hyperpigmentation", "remarkable pigmentation"]}
{"id": "CaseReportBench:train-335", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'CASE REPORT': 'A 4-year-male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy. His birth was at full-term from an uneventful pregnancy. On detailed history the child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation. Neurological examination revealed mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child. Skeletal, dental, eye/ fundus examination and eye or limb movements were normal. Child had a normal head circumference for his age. Skin examination showed scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face. Chest radiograph and all routine hematological investigations were normal. Electroencephalogram (EEG) was normal. Patient was sent for the MRI of brain. MRI was done on 0.2 tesla Signa (GE systems, USA) MRI with T2W, T1W, FLAIR sequences in all three planes. The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All these clinical and radiological findings were diagnostic of Sjogren-Larsson syndrome.'}", "questions": ["Describe the gestational age at birth and indicate whether any complications occurred during the pregnancy."], "ground_truth_arguments": ["His birth was at full - term from an uneventful pregnancy."]}
{"id": "CaseReportBench:train-617", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'CASE REPORT': \"A two-month-old female infant was transferred to Seoul National University Children's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg (<3rd percentile). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion. The initial laboratory findings after birth showed the following increased values on the liver function test: aspartate aminotransferase (AST), 176 U/L; alanine aminotransferase (ALT), 106 U/L; total bilirubin, 1.76 mg/dL; and direct bilirubin, 1.2 mg/dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non-diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract. The patient was fed with preterm formula milk without feeding intolerance. No definitive sepsis event occurred during her hospitalization. When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg/dL and a direct bilirubin level of 9.61 mg/dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum-ascites-albumin gradient level was elevated, and portal hypertension was suspected. By the age of 70 days, the infant was transferred to our hospital for further evaluation of persistent ascites suggesting portal hypertension and hyperbilirubinemia. On the day of admission to our unit, the infant's height was 42 cm (<3rd percentile), her weight was 2.9 kg (<3rd percentile), and her head circumference was 33.5 cm (<3rd percentile). A physical examination indicated whole-body jaundice, a markedly distended abdomen with ascites and an umbilical hernia. The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g/dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg/dL, a direct bilirubin level of 6.4 mg/dL, an AST level of 225 U/L and an ALT level of 114 U/L. The albumin level was 2.4 g/dL, and the ammonia level was increased to 149 µg/dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng/mL (normal values are 14.0-647.2 ng/mL), and the transferrin saturation was 97.2%. The serum alpha-fetoprotein level was in the high normal range (19,737.27 ng/mL; normal values are 40-19,953 ng/mL). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging (MRI) verified a diffuse heterogeneous low signal intensity in the liver on T2-weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra-hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non-diagnostic findings. The infant received supportive medical treatment, including fat-soluble vitamins, ursodeoxycholic acid, fresh frozen plasma, lactulose, diuretics, and sodium benzoate. Her general condition and coagulopathy were aggravated, and her vital signs were unstable. She was transferred to the intensive care unit on day 18 of hospitalization for further management. Her mother began the donor evaluation process. Active gastrointestinal bleeding was observed on day 21 of the infant's hospitalization, and an emergency living donor liver transplantation was performed. The infant was 3 months old, and her weight was 3 kg on the day of transplantation. The graft was tailored by reducing its left lateral section. The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining. The infant fully recovered from hepatic failure after liver transplantation. The infant was discharged one month after the operation. She exhibited normal renal function after transplantation. She received medical treatment for hyperkalemia, which occurred after the administration of tacrolimus. Following her discharge, the patient's neurological development was delayed, and she entered rehabilitation with outpatient clinic follow-up in the hospital's neurology department. Assessments by brain MRI and chromosomal study produced normal findings.\"}", "questions": ["What was reported about the infant's neurological development after discharge?", "What were the findings of the brain MRI and chromosomal studies performed during follow‑up?"], "ground_truth_arguments": ["neurological development was delayed", "brain MRI and chromosomal study produced normal findings."]}
{"id": "CaseReportBench:train-24", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["What age group does the patient belong to at presentation?"], "ground_truth_arguments": ["26 - year - old"]}
{"id": "CaseReportBench:train-346", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'CASE REPORT': 'A 4-year-male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy. His birth was at full-term from an uneventful pregnancy. On detailed history the child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation. Neurological examination revealed mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child. Skeletal, dental, eye/ fundus examination and eye or limb movements were normal. Child had a normal head circumference for his age. Skin examination showed scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face. Chest radiograph and all routine hematological investigations were normal. Electroencephalogram (EEG) was normal. Patient was sent for the MRI of brain. MRI was done on 0.2 tesla Signa (GE systems, USA) MRI with T2W, T1W, FLAIR sequences in all three planes. The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All these clinical and radiological findings were diagnostic of Sjogren-Larsson syndrome.'}", "questions": ["What was the child's head circumference compared to age‑appropriate norms?"], "ground_truth_arguments": ["normal head circumference for his age"]}
{"id": "CaseReportBench:train-453", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}", "questions": ["What neurological symptoms did the patient present with?", "How were the patient's reflexes and sensory examinations described?"], "ground_truth_arguments": ["encephalopathy, fatigue, muscle weakness", "All reflexes were preserved and sensations were normal"]}
{"id": "CaseReportBench:train-345", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'CASE REPORT': \"A 22-month-old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control. She was born at full term through normal vaginal delivery. She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time. Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement ( Fig. 1 ). Developmental regression was similar to that in GM2 gangliosidosis, such as Tay-Sachs disease and Sandhoff disease. The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A (%) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol/hr/mg (reference range, 620–1,000 nmol/hr/mg) and 74.3% (reference range, 55%–72%), respectively. Based on these findings, the patient was diagnosed with Sandhoff disease. However, the patient did not show cherry red spot on fundoscopy. At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable ( Fig. 2 ). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale (MAS). Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross-motor domain, by 3 months in language and fine motor domain, and by 2 months in personal-social interaction domain in the Denver Developmental Screening Test II. Dietary assessment revealed that the patient irregularly ingested a soft and blended diet of 70–130 kcal, five times a day, and the mean eating duration was approximately 1 hour. She had difficulty in eating and she showed signs of aspiration (e.g., coughing, gagging). Moreover, she had a poor feeding posture with inadequate trunk and head support. Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas. The patient underwent videofluoroscopic swallowing study (VFSS), and was given barium-containing free water, yogurt (thick liquid), and rice porridge (soft). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time (1.3 seconds) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing ( Fig. 3 ). The patient's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight-for-height Z-score (−0.3) was in the 15th–50th percentile of the World Health Organization (WHO) growth standards. Nutritional evaluation showed that the patient needed a regular daily intake of 989 kcal. However, she could only consume 700 kcal/day, which was less than the required caloric intake. The patient was given supplementary balanced nutrition twice a day. The patient received an intensive dysphagia rehabilitation program for 30 minutes a day, five times a week, for 6 weeks, and it comprised both direct and indirect interventions, such as oromotor facilitation, thermo-tactile stimulation, and lip strengthening, and compensatory techniques, such as postural modification and alteration of the feeding utensil to facilitate swallowing. She was given anti-spasticity drugs for managing spasticity and achieving a stable posture during feeding. After the treatment, she was fed in a semi-reclined position, which reduced the signs of aspiration and the amount of food or liquid leakage from the mouth. However, her nutritional status showed no improvement, with her daily calorie intake decreasing to 600 kcal/day after 4 weeks of admission. At 6 weeks postadmission, her total intake further decreased to 392 kcal/day. Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight-for-height Z-score (−1.6) decreased to the 3rd–15th percentile of the WHO growth standards, which was a sharp decrease of one major percentile line in a short period. Gastrostomy was therefore recommended, but her parents refused the procedure. She was then referred to another hospital for treatment of deconditioning due to dehydration, and she received gastrostomy.\"}", "questions": ["What knee hyperextension deformity was observed in the patient’s lower extremities?"], "ground_truth_arguments": ["genu recurvatum"]}
{"id": "CaseReportBench:train-167", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case report': 'We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. The Saudi female patient in the UK developed recurrent bouts of abdominal pain, nausea, and vomiting during first pregnancy, diagnosed as hyperemesis gravidarum, and was treated with IV fluids and antiemetics. There was improvement in the condition and the patient delivered a healthy child (in Saudi). After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatremia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities. She was intubated for 3 days. Initial postextubation, physical examination result was unremarkable except for unexplained behavioral disturbances and lower limb weakness. Initial instigations showed sodium levels ranged between 118–125 mmol/L (135–144 mmol/L), mildly elevated transaminases (aspartate aminotransferase/alanine transaminase), and slight elevation of anti-neutrophil antibodies of the perinuclear type (P-ANCA). Alkaline phosphatase, bilirubin, complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid (CSF) analysis findings were all within normal range. The abdominal imaging result was normal, except for contracted gallbladder and stones. Urine became dark red on exposure to light. Total porphyrins in urine were elevated: 29,100 nmol/24 hours (normal: ≤214), with main elevation in uroporphyrin level, 24,200 nmol/24 hours (normal: ≤30), and mild elevation in coproporphyrin level, 118 nmol/24 hours (normal: ≤38). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene (c. 760delC p.L254X). The patient was treated with intravenous heme arginate (4 mg/kg/day) for 5 days, that was followed by an improvement in the chemical and clinical parameters.'}", "questions": ["What gastrointestinal condition was initially suspected in the patient?", "What definitive diagnosis of a gallbladder disorder was established during the clinical course?", "What abdominal symptoms did the patient experience, specifically regarding pain, nausea, and vomiting?", "Describe any episodes of severe abdominal pain the patient had and any diagnoses that were made as a result.", "What abnormalities were observed on abdominal imaging of the gallbladder, such as size or presence of stones?"], "ground_truth_arguments": ["suspected acute cholecystitis", "acute cholecystitis", "abdominal pain, nausea, and vomiting", "bout of severe abdominal pain ( diagnosed as cholecystitis )", "contracted gallbladder and stones"]}
{"id": "CaseReportBench:train-441", "dataset": "CaseReportBench", "role": "Lymphatic-System", "document": "{'Case History': 'A 12-year-old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family. Her general physical examination showed low height for age, proptosis, webbing of neck, hepatomegaly, and normal genitalia. Skeletal examination was normal. Auditory evaluation revealed bilateral sensorineural hearing loss. On mucocutaneous examination well-defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally. Routine laboratory investigations revealed ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g/dl, and a platelet count of 5.14 lakhs/cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post-prandial blood sugar levels were normal. Anti-nuclear antibodies’ titer was negative. Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate. An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein. In view of the constellation of findings summarized in Table 1, we made the diagnosis of H syndrome.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What neck abnormalities were noted during the physical examination of the patient?"], "ground_truth_arguments": ["webbing of neck"]}
{"id": "CaseReportBench:train-414", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case 2': \"A 13-year-old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks. On examination, there were severe atrophic scars on the face and exposed parts of the extremities, which had resulted in mutilating deformities of the fingers. Hypertrichosis, pigmentation, and milia formation were also present on the face. Though erythrodontia was not spotted with the naked eyes, the teeth revealed a pink-red fluorescence under Wood's lamp. Histopathological examination of an intact bulla revealed the subepidermal location of the blister. A clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity, blistering, and hypertrichosis. The early onset and the mutilation of the fingers were highly suggestive of CEP. The patient was investigated. Routine investigations, including liver and renal function tests, were within normal limits except for mild anemia (Hb 8.0 g/dl, reticulocyte count 7% of circulating erythrocytes). ELISA for HIV was negative. PBG was normal in urine. On screening with a spectrophotometer, urinary total porphyrin was 1187 nmol/mmol of creatinine (normal <35 nmol/mmol). Twenty-four-hour urinary levels of uroporphyrin and coproporphyrin were raised. The erythrocytic porphyrins showed a level of 124.3 μg/100 ml (reference value less than 40 μg/100 ml using the hematofluorometric method). A diagnosis of CEP was made.\", 'Case 1': \"A 3-year-old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks. On examination, the child's face was badly scarred. There was hypertrichosis on the shoulders, arms, and face. The teeth were of coppery-red color. There were a few intact blisters and crusted lesions on the hands and feet. Atrophic scars were also present on the extremities. On the basis of the history of blistering on the exposed areas since early infancy, healing with atrophic scarring, erythrodontia, and red-colored urine, we made a clinical diagnosis of CEP. Routine investigations were within normal limits except for mild anemia. The urine did not show increased level of porphobilinogen (PBG). Further investigations were not carried out. The child was treated symptomatically.\"}", "questions": ["What color and characteristics did the patients' teeth exhibit under normal visual inspection?", "What fluorescence or color change was observed in the patients' teeth when examined with a Wood's lamp?", "What clinical signs or observations were noted that might indicate abnormal red discoloration of the teeth?"], "ground_truth_arguments": ["erythrodontia was not spotted with the naked eyes, the teeth revealed a pink - red fluorescence under Wood 's lamp", "teeth were of coppery - red color", "erythrodontia"]}
{"id": "CaseReportBench:train-522", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case 2': 'Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady. At the dermatological examination grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region ( Figure 4 ). The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers, confirming the diagnosis of pseudoxanthoma elasticum ( Figure 5 ). Right ophthalmoscopy, retinography and angiography revealed angioid streaks ( Figure 6 ). Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal.', 'Case 1': 'Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family. At the dermatological examination, coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae ( Figure 1 ) were observed. The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis, compatible with the diagnosis of pseudoxanthoma elasticum ( Figure 2 ). Cardiological evaluation did not show changes (normal electrocardiogram and echocardiogram). Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography ( Figure 3 ).'}", "questions": ["What demographic information is provided about the patient?", "When did the skin lesions first appear and in which body region were they initially observed?", "To which additional anatomical sites have the lesions spread over time?", "How are the lesions described (color, size, type) and are they associated with any symptoms?", "What pre‑existing medical conditions or underlying diseases does the patient have?", "Is there any reported family history of similar skin lesions or disorders?"], "ground_truth_arguments": ["Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady.", "Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family."]}
{"id": "CaseReportBench:train-202", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'CASE REPORT': \"A 22-month-old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control. She was born at full term through normal vaginal delivery. She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time. Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement ( Fig. 1 ). Developmental regression was similar to that in GM2 gangliosidosis, such as Tay-Sachs disease and Sandhoff disease. The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A (%) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol/hr/mg (reference range, 620–1,000 nmol/hr/mg) and 74.3% (reference range, 55%–72%), respectively. Based on these findings, the patient was diagnosed with Sandhoff disease. However, the patient did not show cherry red spot on fundoscopy. At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable ( Fig. 2 ). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale (MAS). Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross-motor domain, by 3 months in language and fine motor domain, and by 2 months in personal-social interaction domain in the Denver Developmental Screening Test II. Dietary assessment revealed that the patient irregularly ingested a soft and blended diet of 70–130 kcal, five times a day, and the mean eating duration was approximately 1 hour. She had difficulty in eating and she showed signs of aspiration (e.g., coughing, gagging). Moreover, she had a poor feeding posture with inadequate trunk and head support. Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas. The patient underwent videofluoroscopic swallowing study (VFSS), and was given barium-containing free water, yogurt (thick liquid), and rice porridge (soft). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time (1.3 seconds) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing ( Fig. 3 ). The patient's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight-for-height Z-score (−0.3) was in the 15th–50th percentile of the World Health Organization (WHO) growth standards. Nutritional evaluation showed that the patient needed a regular daily intake of 989 kcal. However, she could only consume 700 kcal/day, which was less than the required caloric intake. The patient was given supplementary balanced nutrition twice a day. The patient received an intensive dysphagia rehabilitation program for 30 minutes a day, five times a week, for 6 weeks, and it comprised both direct and indirect interventions, such as oromotor facilitation, thermo-tactile stimulation, and lip strengthening, and compensatory techniques, such as postural modification and alteration of the feeding utensil to facilitate swallowing. She was given anti-spasticity drugs for managing spasticity and achieving a stable posture during feeding. After the treatment, she was fed in a semi-reclined position, which reduced the signs of aspiration and the amount of food or liquid leakage from the mouth. However, her nutritional status showed no improvement, with her daily calorie intake decreasing to 600 kcal/day after 4 weeks of admission. At 6 weeks postadmission, her total intake further decreased to 392 kcal/day. Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight-for-height Z-score (−1.6) decreased to the 3rd–15th percentile of the WHO growth standards, which was a sharp decrease of one major percentile line in a short period. Gastrostomy was therefore recommended, but her parents refused the procedure. She was then referred to another hospital for treatment of deconditioning due to dehydration, and she received gastrostomy.\"}", "questions": ["Which disease was the patient diagnosed with?", "What sentence in the report states the patient's diagnosis?"], "ground_truth_arguments": ["Sandhoff disease", "the patient was diagnosed with Sandhoff disease ."]}
{"id": "CaseReportBench:train-336", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'CASE REPORT': 'A 25-year-old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up. On evaluating her history, it was found that she was on oral contraceptives for primary amenorrhea since 16 years of age. She had developed facial hair when she was 8-year-old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris. At 16 years, she consulted the doctor for not being able to achieve menarche. She was then advised for a karyotype evaluation, but no endocrinological investigation was carried out. Her karyotype was reported as 45, X{20}/46, XX{80}, based on which a diagnosis of mosaic Turner syndrome was given. She underwent clitoroplasty at 21 years of age and on and off laser hair removal for facial and chest hair. Her hormone profile was done for the 1 st time when she was 23 years old and 17-hydroxy progesterone (17-OHP) level was 1.3 ng/ml (0.2–1.4 ng/ml), cortisol (AM) was 5–6 μg/dl (3.7–9.5 μg/dl) dehydroepiandrosterone sulfate (DHEAS) was 189.6 μg/dl (65–380 μg/dl) and serum total testosterone was 318 μg/dl (20–130 μg/dl) which was highly raised. Thereafter, she was kept on antiandrogen but the cause of raised androgen was not explored. On examination, she was short stature. Her height is 141 cm, weight 47 kg and hirsutism was evident. Her simplified Ferriman–Gallwey score for hirsutism was 9 (≥3). She had underdeveloped breast (Tanner stage II); on pelvic examination, vagina and cervix were healthy, the clitoris was looking normal (clitoroplasty done in past) and urethra was mildly displaced posteriorly. On transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count. Her blood pressure (BP) was normal. Her fasting glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone, and prolactin levels were within normal limits. Virilizing features of pubertal onset with raised testosterone levels in the absence of XY cell line or SRY gene points out an adrenal pathology and at the same time contradicted the diagnosis of mosaic Turner. Hence, we repeated the karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX. A genotype of 46XX with features of virilization; normal levels of 17-OHP, Cortisol, FSH, LH, but increased levels of testosterone; normal BP; hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region; all favoring NCAH. To confirm NCAH, adrenocorticotropic hormone (ACTH) stimulation test was done, which showed basal plasma 17-OHP as 2300 ng/dl and postsynacthen (60 min) as 3400 ng/dl (<900 ng/dl). The raised level of 17-OHP after stimulation was in the range of NCAH and hence the diagnosis of NCAH was reached. For genetic confirmation patient was counseled for mutation study, which the couple declined due to financial constraints. She was started on low dose steroids to suppress the adrenal production of androgens. The patient was recruited for antagonist protocol of in vitro fertilization (IVF) through which 4 mature ova was retrieved. Earlier, she had been counseled for donor oocyte program considering her a case of mosaic Turner.'}", "questions": ["At what age did the patient first notice primary amenorrhea and how long has the amenorrhea persisted?", "What virilizing signs appeared during childhood and adolescence?", "What were the measured levels of 17‑hydroxyprogesterone, morning cortisol, DHEAS, and total testosterone, and how do these values compare with their reference ranges?", "What is the patient’s height and weight, and does she meet criteria for short stature?", "How was hirsutism quantified (Ferriman‑Gallwey score) and what Tanner stage was observed for breast development?", "What were the results of the fasting glucose, FSH, LH, TSH, and prolactin tests?", "Summarize the overall pattern of androgen excess, including the elevated testosterone level and the status of other hormones (17‑OHP, cortisol, FSH, LH) in the presence of virilizing features."], "ground_truth_arguments": ["primary amenorrhea since 16 years of age.", "developed facial hair when she was 8 - year - old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris", "not being able to achieve menarche.", "17 - hydroxy progesterone ( 17 - OHP ) level was 1.3 ng / ml ( 0.2–1.4 ng / ml ), cortisol ( AM ) was 5–6 μg / dl ( 3.7–9.5 μg / dl ) dehydroepiandrosterone sulfate ( DHEAS ) was 189.6 μg / dl ( 65–380 μg / dl ) and serum total testosterone was 318 μg / dl ( 20–130 μg / dl ) which was highly raised.", "short stature", "hirsutism was evident. Her simplified Ferriman – Gallwey score for hirsutism was 9 ( ≥3 ). She had underdeveloped breast ( Tanner stage II )", "Her fasting glucose, follicle stimulating hormone ( FSH ), luteinizing hormone ( LH ), thyroid stimulating hormone, and prolactin levels were within normal limits", "Virilizing features of pubertal onset with raised testosterone levels", "features of virilization; normal levels of 17 - OHP, Cortisol, FSH, LH, but increased levels of testosterone"]}
{"id": "CaseReportBench:train-609", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'Case reports': 'Patient 1 (a woman, 68 years old) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle-brachial pressure index (ABI) at rest of 0.69 on the right and 0.85 on the left. Duplex scan disclosed bilateral calcified short stenosis (>70%) of the superficial femoral arteries (SFAs). Primary angioplasty with stenting of the right SFA was performed ( Fig 1 ), followed 2 days later by angioplasty using a nitinol stent (LifeStent; Bard, Tempe, Ariz) on the left side. The patient was discharged with combined oral antiplatelet medication (aspirin and clopidogrel). Four weeks later, intermittent claudication recurred, and duplex scanning disclosed bilateral thrombosis of the stented SFAs. The patient is currently stable and does not wish to have further treatment. Fig 1 Intraoperative angiography demonstrating stenosis of the left superficial femoral artery (SFA) and the result after angioplasty and stenting. Patient 2 (a woman, 65 years old) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg (<150 m) with an ABI of 0.51 and 0.68 on the right. Duplex scans disclosed significant stenosis (>70%) of the left SFA, and angioplasty of the left SFA with a nitinol stent (LifeStent; Bard) was performed after failure of medical treatment. One day later, duplex scanning confirmed reocclusion (ABI, 0.46) of the stented SFA. After patency was recovered by fibrinolysis ( Fig 2 ), a second stent was deployed, and the patient was discharged initially with low-molecular-weight heparin and clopidogrel. She was later switched to ticagrelor alone. A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan. A femoral-popliteal saphenous bypass was finally performed, and the patient has remained asymptomatic. Fig 2 Angiography showing acute superficial femoral artery (SFA) thrombosis and result after intra-arterial in situ thrombolysis. Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting (S.M.A.R.T. stent; Cordis, Bridgewater, NJ) for stenosis of the right SFA. The patient was discharged with phenprocoumon (3 mg). One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral-popliteal saphenous bypass. Nine years later, her claudication worsened on the left leg, and angioplasty of the SFA was performed. Twelve months later, in-stent stenosis of the left SFA was found, again treated by angioplasty. After 6 months, she was still suffering from claudication and was referred finally for a femoral-popliteal saphenous bypass. Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs. Bilateral angioplasty with stenting (S.M.A.R.T. stent; Cordis) was performed, and he was discharged with aspirin (80 mg/d). Three years later, his maximum walking distance had decreased; duplex scans revealed restenosis on both sides, and bilateral angioplasty was repeated. Restenosis of the right SFA was found shortly after, and a third angioplasty was performed. Three years later, his maximum walking distance had declined further (<150 m), and computed tomography angiography revealed significant restenosis of the left SFA. Since the patient had developed a dense network of collaterals in both legs, a watch and wait policy was decided.'}", "questions": ["How are ankle‑brachial pressure index (ABI) measurements at rest reported in the document, and for which limbs are they provided?", "How are the superficial femoral artery (SFA) lesions described on duplex scanning (e.g., presence of calcification, degree of stenosis, lesion length, laterality)?", "What claudication symptoms and functional limitations are documented for the patients, including severity, walking distance, and any changes over time?", "Did claudication recur after any intervention, and what imaging findings (e.g., occlusion, restenosis) accompanied the recurrence?", "What instances of restenosis, re‑occlusion, or in‑stent stenosis of the SFA are described, and how were they detected (e.g., duplex ultrasound, CTA)?"], "ground_truth_arguments": ["long history of lower limb claudication with an ankle - brachial pressure index ( ABI ) at rest of 0.69 on the right and 0.85 on the left.", "Duplex scan disclosed bilateral calcified short stenosis ( > 70 % ) of the superficial femoral arteries ( SFAs )", "intermittent claudication recurred", "stenosis of the left superficial femoral artery ( SFA )", "severe claudication of the left leg ( < 150 m ) with an ABI of 0.51 and 0.68 on the right", "Duplex scans disclosed significant stenosis ( > 70 % ) of the left SFA", "A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan.", "for stenosis of the right SFA", "duplex scan disclosed a subtotal stenosis in the right SFA", "claudication worsened on the left leg", "in - stent stenosis of the left SFA", "still suffering from claudication", "severe claudication,", "severe stenosis of both SFAs", "maximum walking distance had decreased; duplex scans revealed restenosis on both sides", "Restenosis of the right SFA", "Three years later, his maximum walking distance had declined further ( < 150 m ), and computed tomography angiography revealed significant restenosis of the left SFA"]}
{"id": "CaseReportBench:train-505", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["What is the patient's approximate age group and how would you characterize their health during early childhood?", "Which genetic or chromosomal disorders are reported for the patient?"], "ground_truth_arguments": ["A 20 - year - old Turner syndrome ( TS ) patient with Neurofibromatosis 1 ( NF1 ) and Tuberous sclerosis complex ( TSC ) was apparently normal till five years of age."]}
{"id": "CaseReportBench:train-148", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': \"A 27-year-old nulliparous woman, a diagnosed case of 21-hydroxylase deficient simple virilizing form of classic CAH visited our department from the endocrinology department for pregnancy maintenance. Her diagnosis had been identified at eleven years old with a high testosterone level, raised 17-hydroxyprogeterone level, enlarged clitoris and normal karyotype (46, XX). At the age of 12, she underwent clitoral resection and vaginoplasty at urology department of our hospital. She took dexamethasone (minimum dose 0.5 mg/day to maximum dose 1.0 mg/day) after operation. Four months later, her breasts expanded and in six months' time, menstruation began. The treatment sustained without any other complication. The treatment had continued and urology department referred this case to endocrinology department when she was 27 years old. Medication was changed to prednisolone and the endocrinology department had prescribed it (minimum dose 10 mg/day to maximum dose 20 mg/day) before pregnancy. She married at 25 years old and had a spontaneous abortion at 26 years old. After the abortion, she got pregnant spontaneously without any trial of assisted reproductive technology. At 12+3 week of gestation, she first visited our department. The first trimester screening conducted at the first visit of 12+3 week of gestation was normal and quad test conducted at 16+3 week of gestation was also normal. She was diagnosed with gestational diabetes mellitus as blood sugar was mildly increased than normal range in the 100 g oral glucose tolerance test conducted at 24+6 week of gestation. Lifestyle modification was recommended to the patient and blood sugar was well-controlled without any medication. Ultrasonography was performed at two to four weeks. The development of fetus was appropriate to the gestational age without any sign of intrauterine growth retardation or large for gestational age. During pregnancy, she continued to take prednisolone (minimum dose 7.5 mg/day to maximum dose 20 mg/day) on demand at endocrinology department. Cesarean section was preferred other than vaginal delivery, as she had cephalopelvic disproportion on examination and history of vaginoplasty. She delivered female weighs 2,990 g by elective cesarean section at 38+4 week of gestation. The baby exhibited normal 7 Apgar score and did not require oxygen or respiratory assistance. The external genitalia was normal and there was a sign of normal karyotype (46, XX) in the result of chromosomal study. After the delivery, the patient had took prednisolone (15 mg/day) consistently for the CAH. After one time of spontaneous abortion, 3 years later, at the age of 30, she became pregnant of the second baby spontaneously. She was diagnosed with gestational diabetes mellitus due to the mildly increased level of blood sugar at the 100 g oral glucose tolerance test conducted at 23+4 week of gestation, however, the blood sugar was well-controlled by life style modification without medication. The development of fetus was appropriate to the gestational age and antenatal care did not show any particular sign. During this pregnancy, she continuously took the prednisolone (minimum dose 7.5 mg/day to maximum dose 15 mg/day) prescribed by endocrinology department. She delivered 3,250 g female baby at 38+2 week of gestation, by cesarean section. The baby exhibited normal Apgar score and did not require oxygen or respiratory assistance. Four years old baby and eleventh month old bay have shown normal external genitalia and normal development up to now.\"}", "questions": ["What genital reconstructive surgeries did the patient undergo, and at what ages were they performed?"], "ground_truth_arguments": ["clitoral resection and vaginoplasty"]}
{"id": "CaseReportBench:train-329", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': \"A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency.\"}", "questions": ["What notable abnormalities were reported on the brain MRI?", "What were the principal findings on magnetic resonance spectroscopy of the brain?", "What were the results of the initial cerebrospinal fluid analysis?", "What abnormal metabolites were detected in the follow‑up CSF study?"], "ground_truth_arguments": ["MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N - acetylaspartate ( NAA ) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1 - weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules ( white arrows ). Fig. 1 –. Fig. 2 Axial T2 - weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter ( white arrow ). There is overall low parenchymal volume with prominence of the extra - axial spaces ( black arrow ). Fig. 2 –. Fig. 3 Sagittal T1 - weighted images reveal low parenchymal volume of the superior folia with prominence of the extra - axial spaces ( white arrow ). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N - acetyl aspartate peak.", "CSF analysis yielded an acellular CSF with normal protein and glucose", "follow - up study of the patient 's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside"]}
{"id": "CaseReportBench:train-277", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'CASE DESCRIPTION': \"A 41-yr-old man was referred to our emergency room from a local clinic on July 3, 2006, with the impression of acute viral hepatitis due to a remarkable elevation of liver enzymes. He had experienced generalized weakness, dark urine, and jaundice for a two week period. His previous history included community-acquired pneumonia and carpal tunnel syndrome, but neither diabetes mellitus nor hypertension. He complained of impotence, and his mother described precocious puberty and hirsutism beginning at the age of 7. He was not married and had no children. His vital signs were a blood pressure of 115/92 mmHg, a regular pulse of 105/min, and a respiratory rate of 18/min. His height was 152.5 cm (< 3th percentile) and body weight was 72.5 kg. The body mass index was 32.5. Acanthosis nigricans was present in both axillae, and there was central obesity with erythematous, scaly, guttate papules on the lower abdominal skin. He also had a rather ambiguous buffalo hump; however, moon face or red stria was not present ( Fig. 1 ). Total and direct bilirubin levels were elevated at 11.6 mg/dL and 8.6 mg/dL, respectively. The AST and ALT levels were 224 and 1,044 U/L, respectively. Serum BUN level was 9.7 mg/dL, and serum creatinine level was 0.82 mg/dL. Serum electrolytes were normal. Based on a positive anti-HAV IgM titer, he was diagnosed with acute hepatitis A. During the evaluation to exclude other causes of liver dysfunction, a 4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT ( Fig. 2A, B ). We evaluated the endocrine function ( Table 1 ). Twenty-four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements (226.4 µg/24 hr; 122.1 µg/24 hr). Plasma cortisol was within the normal range (7.4 µg/dL), however, ACTH level was very high (676.5 pg/mL). Urine 17-OHCS and 17-ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated (0.414 ng/mL). DHEA-S was within the normal range (1.88 µg/mL). Based on the high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass, we suspected a pituitary corticotrophic adenoma with marked asymmetric adrenal hyperplasia. To confirm the diagnosis of Cushing's syndrome, low- and high-dose dexamethasone suppression tests were performed. Then, 24-hr urine cortisol was markedly suppressed, not only by high-dose dexamethasone but also by low-dose dexamethasone ( Table 2 ); this result essentially eliminates the diagnosis of Cushing's syndrome ( 7, 8 ). We thus suspected CAH based on the short stature, precocious pubarche and marked suppression of 24-hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH. The testosterone level was normal (3.51 ng/mL), but 17α-hydroxyprogesterone (17-OHP) was markedly elevated to 30,000 ng/dL, strongly supporting the diagnosis of a simple virilizing form of CAH. Gene analysis revealed CAH due to 21-hydroxylase deficiency by a compound heterozygote for CYP21 mutations: Ile173Asn (I173N) and Arg357Trp (R357W) ( Fig. 3 ), confirming the diagnosis of a simple virilizing from of CAH due to mutations in CYP21 . We began administration of adrenal steroids. After 6 months of treatment with dexamethasone (0.25 mg daily), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig. 2C, D ). 17-OHP and ACTH levels were normalized to 118 ng/dL and 20.8 pg/mL, respectively, and impotence was improved.\", 'Mutation analysis': \"Genomic DNA was extracted from the peripheral blood leukocytes of patient by using the Wizard Genomic DNA Purification Kit according to the manufacturer's instructions (Promega, Madison, WI, USA). All exons of the CYP21 gene were amplified by PCR on a thermal cycler (Applied Biosystems, Foster City, CA, USA). Direct sequencing was performed using the BigDye Terminator Cycle Sequencing Ready Reaction kit and an ABI Prism 3130 Genetic Analyzer (Applied Biosystems). The sequences were analyzed using the Sequencer program (Gene Codes Corp., Ann Arbor, MI, USA) and were compared to the reference sequences. The numbering of nucleotide positions was done according to the CYP21 DNA sequence, and the Gen-Bank accession number was NM000500.\", 'Biochemical assays': 'Blood samples were obtained in the morning after an overnight fast and a 30-min resting period in the supine position. Hormones were assayed using IRMA kits. For low- or high-dose dexamethasone suppression test, 0.5 or 2 mg dexamethasone was administered 4 times a day for 2 consecutive days.'}", "questions": ["What urinary abnormalities did the patient experience?", "What sexual dysfunction did the patient report, and how did it change after treatment?", "Were there any abnormalities in the patient's renal function labs (BUN and creatinine)?", "What was the status of the patient's serum electrolyte levels?"], "ground_truth_arguments": ["dark urine", "impotence,", "Serum BUN level was 9.7 mg / dL, and serum creatinine level was 0.82 mg / dL. Serum electrolytes were normal.", "impotence was improved"]}
{"id": "CaseReportBench:train-254", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': 'A 19 year old boy presented with bilateral slow growing and painful swellings of his achilles tendons of 4 year duration. On clinical examination each swelling was of size 5×2 cm, firm, nodular, tender and localized to the distal portion of the tendoachilles just above its insertion point to the calcaneal tuberosity ( Fig. 2 ). He was more symptomatic on the right side. He was initially advised rest, analgesics and foot wear modification. However, the symptoms did not subside and the situation worsened resulting in significant disability with limitation of his walking distance. Initial radiographs of both ankles showed homogenous soft tissue shadow in the lower halves of tendoachilles ( Fig. 3 ). Magnetic resonance imaging showed localized homogenous hyper intense signals with fusiform swellings of tendoachilles ( Fig. 4 ). Surgical excision was offered and the right sided one was selected first as it was more symptomatic. The swollen tendinous portion measuring 6×3 cm was excised ( Fig. 5 ) followed by reconstruction using the ipsilateral peroneus brevis tendon. Immediate and early post-operative period was uneventful. Biopsy of the excised specimen revealed it to be a xanthoma characterized by the accumulation of mononuclear cells with foamy cytoplasm and multinucleated giant cells with high concentration of cholestanol. Thus a diagnosis of cerebro-tendinous xanthomatosis was made. On detailed retrospective inquiry, he had surgery for bilateral juvenile cataracts at the age of 8, along with history of chronic intractable diarrhea. He was coherent and co-operative but slow cerebrated with low intelligence. There were no central nervous system symptoms like convulsions, abnormal gait or incoordination of movements. Family history revealed that he was a child of a consanguineous marriage. Other sibling, a girl was normal. He was short statured measuring 144 cm in height ( Fig. 1 ), thin built with a peculiar yellow conjunctiva. Hematological and biochemical investigations including liver function tests, lipid profile, thyroid function tests and ultrasound examination of abdomen were normal. A special test - serum cholestanol level was elevated to 4.37 mg/dL (normal value: 0.02-0.12 mg/dL). Based on the clinical picture, pathological and serological analysis, the diagnosis of cerebro-tendinous xanthomatosis was confirmed and was kept on medical therapy with chenodeoxycholic acid (CDCA), a synthetic bile acid. RESULT: He was kept under regular follow up with neurologic and neuropsychological evaluation, musculoskeletal examination and serum cholestanol estimation. He started to improve after 3 months of continued medication. According to the latest follow up of 23 months, he achieved complete improvement in his mental status and normal values of serum cholestanol. The pain on the left (non-operated) tendoachilles disappeared completely although swelling persisted. His walking distance improved. However, had reappearance of the swelling in the reconstructed tendon on the right side, although was not painful ( Fig. 6 )', 'Case Report:': 'We find such a rare and perplexing case in a 19 year boy who presented with painful swellings of both achilles tendons causing signification limitation of walking distance. This was initially interpreted as a localized benign disorder and was offered surgical treatment. Excision of the swollen achilles tendon followed by reconstruction using peroneus brevis tendon was done, first on the more symptomatic right side. The diagnosis of cerebrotendinous xanthomatosis was made retrospectively after histopathological as well as biochemical analyses and appropriate medical therapy was initiated.'}", "questions": ["What chronic gastrointestinal symptoms did the patient experience?"], "ground_truth_arguments": ["history of chronic intractable diarrhea"]}
{"id": "CaseReportBench:train-479", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Diagnoses:': 'The proband underwent a thorough examination in our hospital and was diagnosed as mitochondrial encephalomyopathy. The proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene. Although his parents did not carry the mutation.', 'Case presentation': \"The proband was a 12-year-old boy on first visiting to our hospital. The proband was the first and the only child of his healthy, nonconsanguineous parents of Han Chinese descentand was born at 38 weeks gestation by spontaneous delivery. The proband had no postnatal adaptation, and the Apgar score was unknown. He was admitted to the hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after the treatment of unexplained fever and somnolence. The highest temperature was 37.8°C, accompanied by vomiting 4 to 5 times on the same day, with insufficient spirits. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of our hospital (no. 2018021). Informed written consent was obtained from all participants prior to their enrollment in this study. The proband underwent a thorough examination in our hospital, including electroencephalogram, echocardiogram, electrocardiogram, brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), physical examination, laboratory examination, and mitochondrial gene detection. Genomic DNA from the family was extracted from peripheral whole blood samples using the genomic DNA extraction kit (Qiagen) according to the manufacturer's instructions. The entire mitochondrial genomes of the family were PCR amplified in 24 overlapping fragments by using sets of the light strand and the heavy strand oligonucleotide primers, as described elsewhere. Each fragment was purified and subsequently Sanger sequencings were conducted by TSINGKE Biological Technology(Beijing, China). The resultant sequence data were compared with the revised consensus Cambridge sequence (GenBank accession no. NC-012920). His electroencephalogram showed clear increase of 4–5c/s theta waves, 2–3c/s delta waves, with a small amount of sharp waves. His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right (Fig. 1 A). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS (Fig. 1 B). Normal structure and ejection fraction were observed via echocardiography. Serum lactate dehydrogenase, creatine kinase, α-hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range. Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation (Fig. 2 ). The patient was treated according to the diagnosis of mitochondrial encephalomyopathy. Intravenous acyclovir, ceftriaxone and dexamethasone were used for antiviral, antimicrobial, and anti-inflammatory therapy, respectively. Intravenous mannitol was gradually tapered for reducing intracranial pressure with furosemide for inducing diuresis. Intravenous arginine could help to treat alkalosis and supple some essential amino acids. Oral oxiracetam capsules, vitamin B1, and coenzyme Q10 were used for providing nutrition and improving energy. His medications were 30 mg vitamin B1, 0.1gm vitamin C and mecobalamin 750 μg daily after discharge from our hospital. The patient was able to walk and talk slowly with improved writing skills and no stroke-like episodes. The neurological examination was negative and muscle tension was identified as grade V.\", 'Patient concerns:': \"A 12-year-old boy was admitted to Shaoxing People's Hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after treatment of unexplained fever and somnolence.\"}", "questions": ["What speech, language, writing, word‑recognition, dressing, and gait abnormalities did the patient present with?", "Describe the patient's level of consciousness, including any episodes of somnolence or reduced energy.", "What abnormalities were reported on the patient's electroencephalogram?", "What findings were observed on brain MRI and on proton magnetic resonance spectroscopy?", "What were the cerebrospinal fluid analysis results, including cell counts, chloride, protein, and glucose levels?", "What did the neurological examination reveal after treatment?", "How did the patient's functional status change after treatment regarding walking, speech, writing ability, and occurrence of stroke‑like episodes?"], "ground_truth_arguments": ["a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking", "and somnolence.", "insufficient spirits.", "His electroencephalogram showed clear increase of 4–5c / s theta waves, 2–3c / s delta waves, with a small amount of sharp waves", "His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right ( Fig. 1 A ). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS", "In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range", "able to walk and talk slowly with improved writing skills and no stroke - like episodes", "neurological examination was negative", "reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking", "somnolence."]}
{"id": "CaseReportBench:train-266", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case report': \"A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission.\"}", "questions": ["Has the identified STAR gene variant been previously reported in the literature?"], "ground_truth_arguments": ["This variant has been previously reported in association with CLAH ."]}
{"id": "CaseReportBench:train-442", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["What cardiac conduction abnormality and rhythm characteristics led to the decision to implant a pacemaker in this Kearns Sayre Syndrome patient?", "Describe the type of pacing system and lead configuration implanted, and summarize how the pacemaker was programmed (e.g., pacing mode and general rate parameters)."], "ground_truth_arguments": ["As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra - Hisian rhythm he was implanted with a dual chamber transvenous pacing system ( St Jude 's Accent MRI system with 52 cm ( atrial ) and 58 cm ( ventricular ) St Jude Tendril MRI leads ) . The pacemaker was set in DDD mode with a lower rate of 50 / min , a maximum sensor rate of 110 / minute and an upper tracking rate of 130 / minute ."]}
{"id": "CaseReportBench:train-420", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': 'We report a case of a 40-year-old man with CAH/21-hydroxylase deficiency, who willingly interrupted Prednisolone therapy for years. In 2007 his left adrenal gland was removed and diagnosed with adrenocortical carcinoma. In 2012 CT scan ( Fig. 1 ) showed a tumor in the right adrenal gland, confirmed in 2013 by MRI, with retroperitoneal lymphadenomegaly. Serum hormonal screening showed high 17-OH progesterone and ACTH. The patient refused operation. He was referred to us from another hospital because of a synchronous progressive enlargement of bilateral testicular masses during substitutive medical therapy ( Fig. 2 ). Serum tumor markers at 12.09.2013: AFP 10.56 IU/mL (AFP 4.03 IU/mL 01.2012), hGT beta and CEA – not elevated, semen analyses: azoospermia. Considering the possibility of malignant testicular neoplasm, the patient underwent bilateral orchiectomy, because the frozen sections were interpreted as malignant tumors. Gross findings: right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds (0.1–1.5 cm). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin-α were positive in 50% of the cells. There were no mitotic figures on HE-staining (Ki 67 negative). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated. We excluded primary germ cell testicular tumors and anaplastic large cell lymphoma, metastatic nonsecreting pheochromocytoma. “TARTs” was the appropriate diagnosis. There was still suspicion for metastatic adrenocortical carcinoma because of the CT and MRI findings. In order to prove the diagnosis the patient agreed to the surgical removal of his right adrenal gland in 01.2014. Adrenocortical carcinoma was histologically diagnosed again at other hospital. We revised all slides and performed immunohistochemical analyses. In the left adrenal gland we found polygonal cells with mild nuclear pleomorphism, conspicuous nucleoli, abundant eosinophilic granular cytoplasm, some with lipochrome pigments, without mitotic activity (Ki 67 positive in <1% of nuclei). The clear cell component was about 26%. In CAH, marked diffuse hyperplasia of zona fasciculata is a result of ACTH stimulation. There is also a conversion of zona fasciculata cells into zona reticularis-type cells (lipid-depleted). The cells exhibited strong positive expression for vimentin, Melan A and inhibin. In the right adrenal gland microscopically we found fields and circumscribed but nonencapsulated nodules that protruded into the adjacent fat, consisting of fasciculata-type cells and nodules composed of zona reticularis-type cells with lipofuscin. Nuclear and cellular pleomorphism was more prominent than in the left adrenal gland. Mitoses necrosis, hemorrhage, sinusoidal, vascular and capsular invasion were not found. The required number of morphological criteria, according to Weiss and Aubert, to classify the lesion as carcinoma, were not met. 2 Revised diagnosis: CAH bilateral adrenal cortical hyperplasia of a diffuse and nodular type with multiple bilateral cortical nodules, pigmented nodules and congenital adrenal cytomegaly and bilateral TARTs revealing morphologically similar changes.'}", "questions": ["What is the patient’s age, gender, and congenital adrenal hyperplasia (CAH) subtype?", "Which long‑term medication did the patient stop taking, and for how long had it been interrupted?", "What adrenal surgery was performed in 2007 and what pathology was identified from the specimen?", "What type of testicular surgery was reported, and was it performed on one or both testes?", "When did the patient undergo surgical removal of his right adrenal gland, and what was the intended diagnostic purpose?"], "ground_truth_arguments": ["We report a case of a 40 - year - old man with CAH/21 - hydroxylase deficiency, who willingly interrupted Prednisolone therapy for years. In 2007 his left adrenal gland was removed and diagnosed with adrenocortical carcinomabilateral orchiectomy", "surgical removal of his right adrenal gland"]}
{"id": "CaseReportBench:train-509", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}", "questions": ["For each patient, list the demographic details: age (in years or months), gender, birth order (e.g., first child, second child), whether the parents are related, and delivery method (cesarean, vaginal, etc.). Provide each fact only once per patient.", "For each patient, state the age at which joint swelling was first observed and enumerate the specific joints that were reported as swollen at that initial time point. List each joint only once.", "For each patient, indicate whether the document mentions head‑drop attacks. If mentioned, reproduce the exact wording used in the source text; if not mentioned, state “not mentioned.”", "For each patient, summarize respiratory‑distress information: total number of admissions for respiratory distress, any interventions reported (e.g., ICU admission, tracheostomy, mechanical ventilation), and the final outcome (survived or died). Report each element once per patient.", "For each patient, identify any family history of rheumatic or autoimmune disease, naming the relative(s) and the specific condition(s) described. List each family‑history item only once."], "ground_truth_arguments": ["This patient was a 4 - year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added", "Reports of head drop attacks were found in the history", "This patient was a 4 year - old girl, first child of a non - related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles", "admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old", "This patient was a 9 - month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient ’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands"]}
{"id": "CaseReportBench:train-317", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE DESCRIPTION': \"A 41-yr-old man was referred to our emergency room from a local clinic on July 3, 2006, with the impression of acute viral hepatitis due to a remarkable elevation of liver enzymes. He had experienced generalized weakness, dark urine, and jaundice for a two week period. His previous history included community-acquired pneumonia and carpal tunnel syndrome, but neither diabetes mellitus nor hypertension. He complained of impotence, and his mother described precocious puberty and hirsutism beginning at the age of 7. He was not married and had no children. His vital signs were a blood pressure of 115/92 mmHg, a regular pulse of 105/min, and a respiratory rate of 18/min. His height was 152.5 cm (< 3th percentile) and body weight was 72.5 kg. The body mass index was 32.5. Acanthosis nigricans was present in both axillae, and there was central obesity with erythematous, scaly, guttate papules on the lower abdominal skin. He also had a rather ambiguous buffalo hump; however, moon face or red stria was not present ( Fig. 1 ). Total and direct bilirubin levels were elevated at 11.6 mg/dL and 8.6 mg/dL, respectively. The AST and ALT levels were 224 and 1,044 U/L, respectively. Serum BUN level was 9.7 mg/dL, and serum creatinine level was 0.82 mg/dL. Serum electrolytes were normal. Based on a positive anti-HAV IgM titer, he was diagnosed with acute hepatitis A. During the evaluation to exclude other causes of liver dysfunction, a 4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT ( Fig. 2A, B ). We evaluated the endocrine function ( Table 1 ). Twenty-four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements (226.4 µg/24 hr; 122.1 µg/24 hr). Plasma cortisol was within the normal range (7.4 µg/dL), however, ACTH level was very high (676.5 pg/mL). Urine 17-OHCS and 17-ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated (0.414 ng/mL). DHEA-S was within the normal range (1.88 µg/mL). Based on the high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass, we suspected a pituitary corticotrophic adenoma with marked asymmetric adrenal hyperplasia. To confirm the diagnosis of Cushing's syndrome, low- and high-dose dexamethasone suppression tests were performed. Then, 24-hr urine cortisol was markedly suppressed, not only by high-dose dexamethasone but also by low-dose dexamethasone ( Table 2 ); this result essentially eliminates the diagnosis of Cushing's syndrome ( 7, 8 ). We thus suspected CAH based on the short stature, precocious pubarche and marked suppression of 24-hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH. The testosterone level was normal (3.51 ng/mL), but 17α-hydroxyprogesterone (17-OHP) was markedly elevated to 30,000 ng/dL, strongly supporting the diagnosis of a simple virilizing form of CAH. Gene analysis revealed CAH due to 21-hydroxylase deficiency by a compound heterozygote for CYP21 mutations: Ile173Asn (I173N) and Arg357Trp (R357W) ( Fig. 3 ), confirming the diagnosis of a simple virilizing from of CAH due to mutations in CYP21 . We began administration of adrenal steroids. After 6 months of treatment with dexamethasone (0.25 mg daily), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig. 2C, D ). 17-OHP and ACTH levels were normalized to 118 ng/dL and 20.8 pg/mL, respectively, and impotence was improved.\", 'Mutation analysis': \"Genomic DNA was extracted from the peripheral blood leukocytes of patient by using the Wizard Genomic DNA Purification Kit according to the manufacturer's instructions (Promega, Madison, WI, USA). All exons of the CYP21 gene were amplified by PCR on a thermal cycler (Applied Biosystems, Foster City, CA, USA). Direct sequencing was performed using the BigDye Terminator Cycle Sequencing Ready Reaction kit and an ABI Prism 3130 Genetic Analyzer (Applied Biosystems). The sequences were analyzed using the Sequencer program (Gene Codes Corp., Ann Arbor, MI, USA) and were compared to the reference sequences. The numbering of nucleotide positions was done according to the CYP21 DNA sequence, and the Gen-Bank accession number was NM000500.\", 'Biochemical assays': 'Blood samples were obtained in the morning after an overnight fast and a 30-min resting period in the supine position. Hormones were assayed using IRMA kits. For low- or high-dose dexamethasone suppression test, 0.5 or 2 mg dexamethasone was administered 4 times a day for 2 consecutive days.'}", "questions": ["What type of adrenal steroid therapy was administered, and what was the dosing regimen?", "When was the follow‑up evaluation performed relative to the start of dexamethasone treatment?", "What radiologic changes were observed in the bilateral adrenal hyperplasia and the left adrenal mass after treatment?", "How did the serum 17‑hydroxyprogesterone (17‑OHP) level change after therapy?", "How did the plasma ACTH level change after therapy?", "Which clinical symptom related to sexual function showed improvement following the treatment?"], "ground_truth_arguments": ["administration of adrenal steroids . After 6 months of treatment with dexamethasone ( 0.25 mg daily ) , bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig . 2C , D ) . 17 - OHP and ACTH levels were normalized to 118 ng / dL and 20.8 pg / mL , respectively , and impotence was improved ."]}
{"id": "CaseReportBench:train-457", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'The patient was a 41-year-old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age. He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure. His family history was not remarkable. He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age. Three months later, he was admitted to our hospital due to impaired consciousness and vomiting. A neurological examination showed gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities. However, no ophthalmoplegia, hearing loss, or muscle weakness were detected. His mini-mental status examination score was 15/30, and his frontal assessment battery score was 5/18. The findings from routine blood tests including blood sugar and autoimmune antibodies were normal. A laboratory examination showed slightly increased serum pyruvic acid levels (1.2 mg/dL), but his serum lactate levels were normal (14.2 mg/dL). The cerebrospinal fluid lactate (34.8 mg/dL) and pyruvic acid (1.6 mg/dL) levels were elevated. Electrocardiogram and echocardiogram were normal. Brain magnetic resonance imaging (MRI) showed bilateral cortical and subcortical high-intensity lesions on T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion-weighted imaging (DWI) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient (ADC) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H-MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ). 99m Tc-Ethylcysteinate dimer single photon emission computed tomography (SPECT) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions ( Fig. 1E ). We suspected mitochondrial encephalopathy, such as MELAS. A histopathological study of the biopsied right biceps branchii muscle revealed mild variation in the fiber size, measuring from 30 to 90 microns in diameter, which was thought to be a non-specific change. No necrotic or regenerating fibers were seen. On modified Gomori-trichrome stain, ragged red fibers (RRFs) were not observed. Succinate dehydrogenase (SDH) stain revealed no strongly SDH-reactive blood vessels. Cytochrome c oxidase staining revealed no abnormalities ( Fig. 1F ). However, the complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a level of mutant heteroplasmy of 69.5%, in the mitochondrial complex I subunit gene, MT-ND3 ( Fig. 1G ). Because his family had no clinical symptoms suggestive of mitochondrial diseases, we could not conduct a complete mtDNA sequence analysis of his family. Over a two-month period, he experienced two stroke-like episodes with simple partial seizure and vomiting. Each time the stroke-like episodes ended within four days with drip infusion of edaravone and supportive care. To control epileptic seizure, we added levetiracetam (1,000 mg/day) to zonisamide (400 mg/day) and carbamazepine (400 mg/day). Because he had not yet been diagnosed with MELAS-like encephalopathy at that time, we did not administer L-arginine. His higher brain dysfunction and myoclonus worsened with each stroke-like episode.'}", "questions": ["What are the patient's age, gender, and the types of neurological symptoms that began in early adulthood?", "What cerebrovascular and seizure conditions were diagnosed in the patient during his early thirties, and were any systemic features suggestive of a mitochondrial disorder observed?", "What does the patient's family medical history indicate regarding the presence or absence of mitochondrial disease symptoms?", "What new neurological signs emerged in the patient during his early forties?", "What acute clinical findings led to the patient's hospital admission a few months after the recent neurological changes?", "During the following two‑month interval, how many stroke‑like events occurred, what were their general characteristics, and what was the typical duration of each episode?"], "ground_truth_arguments": ["The patient was a 41 - year - old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age", "He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure.", "His family history was not remarkable", "He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age", "Three months later, he was admitted to our hospital due to impaired consciousness and vomiting", "his family had no clinical symptoms suggestive of mitochondrial diseases", "Over a two - month period, he experienced two stroke - like episodes with simple partial seizure and vomiting. Each time the stroke - like episodes ended within four days"]}
{"id": "CaseReportBench:train-356", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Description': 'Polyhydramnios in the second and third trimester of pregnancy is defined by (semiquantative) measurements such as a maximum vertical pocket (MVP) >8 cm, or an amniotic fluid index (AFI) >24 cm. Approximately 90% of cases are idiopathic or caused by gestational diabetes (GDM) 1 . However, 10% of cases are associated with fetal structural abnormalities 2 . Most frequent causes are impaired swallowing from any cause (gastrointestinal, facial, musculoskeletal, or brain abnormalities), cardiac failure, hydrops, and renal abnormalities. Metabolic diseases, such as congenital disorders of glycogen storage, are also incidentally reported to present with polyhydramnios in pregnancy 3 . The usual diagnostic work‐up of polyhydramnios is to exclude GDM and maternal infections, and to perform an extensive structural assessment to rule out fetal anomalies. The presence of structural anomalies, involves increased risk of aneuploidy or other chromosomal and syndromic disorders. In isolated polyhydramnios, the risk of perinatal adverse outcome is, however, still increased when compared with uneventful pregnancies 4 . A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios. Aside from a spontaneously closed ventricular septal defect (VSD) in her own infancy, both parents were healthy. A maternal uncle of the mother had died postnatally of an unknown cause. First‐trimester combined test revealed a low risk for trisomies (NT 1.1 mm). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios (uterine size that outpaced gestational age) and premature contractions. She received tocolytics and corticosteroids for fetal lung maturation. Ultrasound showed polyhydramnios (MVP 9.9 cm, AFI 27.5 cm) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles (11 mm). Amniotic fluid drainage (1.8 L) was performed in an attempt to cease the premature contractions. More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna (12 mm) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm (slightly below p3, with head circumference p50, Fig. 1 A). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD. QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 (11q22.1), including exon 1 of the contactine 5 ( CNTN5 ) gene. This variant is not reported as genomic variant in the normal population, neither known to be associated with a genetic disorder or malformation. A relation with the clinical signs appears unlikely. Maternal serum infection testing (TORCHES) was also normal. Two days later (26 + 0), she spontaneously delivered a boy of 835 g (−0.5 SDS), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively. At birth, he was started on CPAP and transported to the neonatal intensive care unit. Physical examination showed a hypotonic infant with a lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus (Fig. 1 B). He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges. The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels. Testes were not palpable in the scrotum. Postnatal cardiac ultrasound confirmed the presence of a small VSD. Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy. A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome. He developed hypotension and was treated with fluid boluses and inotropic support and antibiotics. Despite stabilization of blood pressure and systemic circulation, he developed a progressive lactate acidosis with extremely high plasma lactate: 19.1 mmol/L and high pyruvate: 269 μ mol/L. The L/P (lactate/pyruvate) ratio was 71, which is strongly increased (normal <20). Organic acid analysis in urine showed a strong increase of lactate (56540 μ mol/mmol creatinine) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal. In the absence of secondary causes, these findings are consistent with primary lactic acidosis, caused by a disorder of the pyruvate metabolism or a mitochondrial respiratory chain defect. Due to the severity of the cumulative problems, the neonate died 2 days after birth. Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst (Figure S1C), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst (Figure S1D). DNA analysis of the PDHA1 ‐gene (most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency) showed no pathogenic mutations. Large deletions, point mutations, and small insertions/deletions in mitochondrial DNA (mtDNA) derived from blood were excluded by next‐generation sequencing (NGS) using the Illumina MiSeq platform and a dedicated bioinformatics pipeline (available on request). For whole exome sequencing, exome enrichment was performed by the Agilent SureSelectXT exome enrichment kit version 4, including the UTR regions. Sequencing was performed by an Illumina HiSeq2000 (San Diego, CA) using a 2 × 100 bp paired‐end recipe. Basecalling, and demultiplexing was done using bcl2fastq 1.8.4.,(Illumina, San Diego, CA) reads were aligned onto the human reference genome (hg19) using BWA 0.5.9., duplicates marked using the PICARD software suite 1.77 (GitHub Enterprise, San Francisco, CA), and variants were called using GATK 2.1‐8. Annotations were added using an in‐house build annotation database, according to UCSC RefGene track, dbSNP137, and the dbNSFP (v2.0). Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing: c.292C>T (p.(Arg98*))and c.1303C>T (p.(Arg435*)). Both are nonsense mutations resulting in a premature stop codon at position p.98 and p.435 of the FBXL4 protein, respectively. The location of these mutations on different alleles (compound heterozygosity) was confirmed by testing the parents. Missense and stop mutations in the FBXL4 gene were reported recently to be associated with severe autosomal recessively inherited mitochondrial encephalomyopathy 5, 6, 7, 8 . Our case is the first case demonstrating a premature prenatal onset of symptoms of FBXL4‐ related mitochondrial encephalomyopathy. The polyhydramnios was the primary sign, leading to the detection of brain abnormalities on more detailed fetal ultrasound examination. This early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements. The cases of FBXL4 ‐related encephalopathy reported so far are characterized by increased serum lactate level, psychomotor delay, hypotonia, failure to thrive, swallowing difficulty, and muscle wasting 6 . Onset of symptoms varied from neonatal onset after term birth, to the age of 14 months 5, 6, 8 . Other reported cases were born at term or premature due to medical intervention for intrauterine growth retardation or reduced fetal movements 5, 6 . The FBXL4 gene is situated on nuclear DNA on chromosome 6q16.1. The FBXL4 mitochondrial protein contains an F‐box in its N‐terminal half, followed by 11 leucine‐rich repeats 9, and is expressed in heart, kidney, liver, lung, pancreas, and placenta 10 . Evidence of the pathogenetic effect of FBXL4 mutations was provided by skeletal muscle biopsies and fibroblasts showing defects in mitochondrial respiratory chain enzyme activities, loss of mitochondrial membrane potential, a disturbance of the dynamic mitochondrial network, and mtDNA depletion 5 . The nonsense mutation p.Arg435* in the FBXL4 gene, present in our patient, was earlier reported in homozygous form in a child of consanguineous parents with early onset mitochondrial encephalopathy, severe hypotonia, cardiomyopathy, MRI abnormalities, increased serum lactate, and premature death 5 . The second mutation detected in our patient (p.Arg98* mutation) has not been reported previously. However, like the other mutation reported, this nonsense mutation leads to nonsense‐mediated decay (NMD, RNA degradation) or a truncated protein 5, 6 . As a result, our patient would have been unable to produce a normal FBXL4 gene product. The mother was pregnant again before exome sequencing had started. Within the prenatal timeframe, exome sequencing lead to the diagnosis of the first child, consequently enabling prenatal diagnosis for the second child. Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child. The VSD in our patient is considered to be a separate finding (familial trait), which is not related to the syndrome. Our case demonstrated a prenatal onset of mitochondrial encephalomyopathy presenting with polyhydramnios, causing premature delivery, and cerebellar atrophy. The neonate was hypotonic and in a poor condition with need for mechanical ventilation, inotropic support, and persistent lactate acidosis. Targeted exome sequencing using a mitochondrial gene panel proved its benefit by revealing compound heterozygous mutations in the FBXL4 gene. Prenatal testing was successfully carried out in the current pregnancy. Direct testing for mutations in the FBXL4 gene should be considered in patients with severe encephalomyopathy with high levels of serum lactate.'}", "questions": ["What genetic findings supported a diagnosis of a mitochondrial disorder in the neonate?", "What genetic alterations were reported as being associated with the encephalopathy in this case?", "How is the encephalopathy described in the report categorized?"], "ground_truth_arguments": ["FBXL4 ‐related encephalopathy"]}
{"id": "CaseReportBench:train-170", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["At what age did the patient first develop clinical manifestations such as the small skin lesions on the face?"], "ground_truth_arguments": ["five years of age"]}
{"id": "CaseReportBench:train-63", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}", "questions": ["Describe any neonatal complications mentioned in the patient's medical history."], "ground_truth_arguments": ["no history of neonatal jaundice"]}
{"id": "CaseReportBench:train-318", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}", "questions": ["Did the patient experience any sleep‑related changes after starting dexamethasone therapy?"], "ground_truth_arguments": ["insomnia"]}
{"id": "CaseReportBench:train-392", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Patient Consent': 'Patient consent was obtained.', 'Case Presentation': 'A 24-year-old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease (CKD) was referred for preconception counseling. Cystinosis was confirmed by an elevated leucocyte cystine level in infancy. Early diagnosis, made possible by cystinosis in an older sibling, and good treatment adherence contributed to delayed kidney disease progression. Electrolyte abnormalities secondary to Fanconi syndrome were treated with daily supplemental dosages of potassium 96 mmol, phosphate 25.2 mmol, and sodium bicarbonate 53.6 mmol. There were no overt extra-renal complications apart from mild photophobia. Her average prepregnancy urine protein-to-creatinine ratio was 132 mg/mmol, α1-microglobulin-to-creatinine ratio was 30.7 mg/mmol, and estimated glomerular filtration rate (eGFR) was 89 ml per minute per 1.73 m 2 . On confirmation of pregnancy, losartan and cysteamine were discontinued. Low-dose aspirin was initiated for the prevention of pre-eclampsia. As expected, proteinuria and eGFR increased during pregnancy. 8 Blood pressure remained normal with no evidence of gestational hypertension or pre-eclampsia. Daily electrolyte supplementation increased to potassium 128 mmol and phosphate 33.6 mmol, with no increase in the dose of sodium bicarbonate. Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein. The pregnancy was complicated by recurrent urinary tract infections (UTIs) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia. After treatment of the complicated UTI, prophylactic oral antibiotics were administered for the remainder of pregnancy without UTI recurrence. She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes. The infant was admitted to the neonatal intensive care unit for 23 days. Cysteamine was reinitiated immediately after delivery and enalapril was initiated at 2 weeks postpartum. The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1-microglobulin-to-creatinine ratio and eGFR were stable ( Figure 1 ). Figure 1 Urinary proteins and eGFR at baseline, during pregnancy and postpartum. eGFR, estimated glomerular filtration rate. While breastfeeding, her delayed-release cysteamine dosage was 675 mg twice daily (0.84 mg/m 2 /d) compared with her prepregnancy dosage of 825 mg twice daily (1.06 mg/m 2 /d). The cysteamine dosage was reduced during breastfeeding as a precaution because of the lack of lactation safety data. She exclusively breastfed for 4 months and discontinued at 5 months. The cysteamine dosage subsequently stabilized at 750 mg twice daily (0.95 mg/m 2 /d). Breastmilk samples were collected and analyzed ( Table 1 and Supplementary Methods ). The calculated relative infant dose was 0.4%. The predicted infant cysteamine dose over 24 hours was 0.52 mg. Infant cysteamine levels were not measured. The infant had normal growth and development at 18 months and a normal leucocyte cystine level. Table 1 Breastmilk cysteamine concentration relative to dose of delayed-release cysteamine bitartrate at steady state Time postdose (h) Breastmilk cysteamine concentration (mg/l) 0 0.12 2 0.76 4 1.87 6 0.51'}", "questions": ["What is the patient's age category at the time of presentation (e.g., adolescent, young adult, etc.)?"], "ground_truth_arguments": ["24 - year - old"]}
{"id": "CaseReportBench:train-22", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Cases': 'The older patient was 20 years old. She was a product of a full-term spontaneous vaginal delivery at home. She was found to have severe virilized external genitalia: a phallic-like structure with hypospadias and incompletely fused labioscrotal folds. She was raised and named as a boy and no medical advice was sought at that time. Her parents reported that she had behaved as a female since early childhood. She was interested in playing with girls and in girl’s games, although she studied at male schools. She spent most of her time with her girlfriends and felt most comfortable when she dressed as a female. She was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation. Physical examination showed a short male-looking adolescent with acne and Tanner stage IV breast development. Her height was 133 centimeters. Her blood pressure was 140/88. Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An adrenocorticotropic hormone (ACTH) stimulation test showed a baseline cortisol (F) level of 28 nmol/L, ACTH of 201 ng/mL (normal, 0–46), 11-deoxycorticosterone (11-DOC) of 20 nmol/L (normal, 0.49–3.3), 17-hydroxyprogesterone (17-OHP) of 17 nmol/L and testosterone (T) of 7 nmol/L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol/L, the 11-DOC level was 141 nmol/L (normal, 2.2–6.8) and the 17-OHP level was 22 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X-ray. Examination under anaesthesia combined with cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus. Based on her biochemical and radiological evaluation, she was diagnosed as having 11-hydroxylase deficiency and was started on hydrocortisone 10 mg twice a day. She was evaluated by the pediatric psychiatrist who clearly confirmed her female gender identity and her strong wish to be converted to a female. Feminizing genitoplasty (clitoral reccesion) was performed at the age of 16 years and she was given a female name. She admitted her strong desire to get married and to be a mother. The younger patient was 16 years old. He was born at home and raised and named as a boy based on the appearance of the external genitalia. His parents reported that he behaved as a male and was proud of that. He was interested in playing with boys and in boy’s sports. He was dressed as a boy and had a short haircut. He was referred to our clinic at the age of 13 years. Physical examination showed a short stature, a masculine appearance, acne and Tanner stage IV pubic hair and stage II breast development. His height was in the fifth centile. His blood pressure was 130/80 mm Hg. Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable. Laboratory evaluation revealed a normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol/L, an ACTH of 231 ng/mL, 11-DOC of 40 nmol/L, 17-OHP of 18 nmol/L and a T level of 7 nmol/L. Sixty minutes after ACTH stimulation, the F level was 45 nmol/L, 11-DOC was 114 nmol/L and 17-OHP was 20 nmol/L. Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years. He was diagnosed as having 11-hydroxylase deficiency and started on hydrocortisone 10 mg twice a day. His final height was 139 centimeters. He was interviewed by the pediatric psychiatrist who clearly confirmed his male gender identity and his strong wish to continue to be raised as a boy. We had several separate meetings with him and his parents and informed them that he would be an infertile man if he decided to continue to be raised as a man and there was a possibility that he would be a fertile women if he converted to his genetic sex. The patient, however, refused to change to his female genetic sex and admitted his strong wish to be a man forever. After more that one year of counseling and intensive psychiatric interview, he and his parents decided on a hysterectomy “to avoid menarche which might affect him psychologically” as his mother said. Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed. Both patients were satisfied by the way they were managed and raised and there were no postoperative psychological complications.'}", "questions": ["Describe the place and mode of delivery for the older (female) patient.", "Describe the place of birth for the younger (male) patient."], "ground_truth_arguments": ["She was a product of a full - term spontaneous vaginal delivery at home", "He was born at home"]}
{"id": "CaseReportBench:train-195", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Cases': 'Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility, accompanied by congenital adrenal hyperplasia ( CAH ). Here are reported two cases of TART s that were referred to Kobe City Medical Center West Hospital for the treatment of infertility and testicular tumors.', 'Case 2': 'A 41 year old man was followed at the local clinic for polycythemia (hemoglobin: 18.0 g/dL; red blood count: 627 × 10 4 ; hematocrit: 53.1%) and hypertension. An abdominal CT scan for the examination of these conditions revealed the enlargement of the bilateral adrenal glands (Figure 5 ). The patient was referred to endocrinologists in the hospital for further investigation. The patient was seen to have obesity (height: 165 cm; weight: 79 kg; Body Mass Index: 29.0 kg/m²). The laboratory tests revealed an extremely high level of ACTH (316.4 pg/mL) and a relatively low level of cortisol (6.8 μg/dL). Although the patient did not have any family history of CAH, the CT findings regarding the adrenal glands, unbalanced pituitary–adrenal hormones, and high level of serum 17‐OHP (62.7 ng/mL) indicated the possibility of CAH. The difference from case 1 is that the first examination was made by endocrinologists, not urologists. The differential diagnosis was made before a testicular examination. The abnormality in the pituitary–gonadal hormonal status (FSH: <0.1 IU/mL; LH: <0.1 IU/mL; testosterone: 10.9 ng/mL; estradiol: 29 pg/mL) indicated the excessive secretion of adrenal androgens. Bilateral testicular tumors were identified in a scrotal ultrasound echo scan and then a urological consultation and several additional examinations were offered in order to rule out a germ cell tumor. At the physical examination, both testes had become slightly atrophied (right: 14 mL; left: 12 mL) (performed with a Prader orchidmeter) and no induration was palpated. All the serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 (Figure 6 A). The semen analysis showed azoospermia. A genetic diagnosis by PCR‐direct sequencing proved CAH due to 21‐hydroxylase deficiency due to CYP21A2 gene mutation. After 6 months of low‐dose, daily oral glucocorticoid therapy (0.5 mg/d), the serum FSH, LH, testosterone, and estradiol levels returned to normal levels (9.2 IU/mL, 1.8 IU/mL, 0.8 ng/mL, and <10 pg/mL, respectively). The polycythemia also improved to a Hb level of 15.2 g/dL. Sperm emerged (concentration: 3.4 × 10 6 /mL; motility: 26%), along with a size reduction in the adrenal hyperplasia and TART (Figure 6 B).', 'Case 1': \"A 41 year old man was referred to Kobe City Medical Center West Hospital, Kobe City, Japan, because of 2 years of infertility. At the physical examination, the patient's physical constitution was as follows (height: 1.58 m; weight: 65 kg; body mass index: 23.9 kg/m²). Both testes had become atrophied (9 mL) (performed with a Prader orchidmeter) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes (Figure 2 A). The semen analysis revealed oligoasthenozoospermia (volume: 2.6 mL; concentration: 7 × 10 6 /mL; motility: 14%). The hormonal examination revealed a normal hormonal status of serum follicle‐stimulating hormone (FSH) of 2.7 mIU/mL, luteinizing hormone (LH) of 1.3 mIU/mL, testosterone of 4.3 ng/mL, and estradiol of 13 pg/mL. All the serum markers for testicular tumors, including human chorionic gonadotropin, alpha‐fetoprotein, and lactate dehydrogenase, were within the normal range. The pelvic magnetic resonance imaging (MRI) scan showed irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image (Figure 3 ). An enhanced computed tomography (CT) scan revealed diffuse, irregular enlargement of both adrenal glands, with no finding in the testes (Figure 4 A,B). Bilateral testicular atrophy and bilateral enlargement of the adrenal glands without any other metastases did not seem to be typical for malignant testicular tumors. At this point, adrenal gland disease was suspected and an endocrinologist was consulted for further examination. In the endocrinological examination, both the serum ACTH and 17‐OHP levels were extremely high (69.3 pg/mL and 112 ng/mL, respectively). Genetic diagnosis by polymerase chain reaction (PCR)‐direct sequencing confirmed the 21‐hydroxylase deficiency due to CYP21A2 gene mutation (I‐172N mutation) and a low‐dose, oral glucocorticoid of 0.5 mg/d was started under the diagnosis of CAH. After 1 month of glucocorticoid therapy of 0.5 mg/d, the semen analysis revealed a significant change (concentration: 34 × 10 6 /mL; motility: 59%), along with normalization of the testicular size (right: 14 mL; left: 16 mL). The size reduction of the TART was identified by ultrasound (Figure 2 B). The hormonal status had not changed significantly from the pretreatment status (serum FSH: 2.8 mIU/mL; LH: 1.6 mIU/mL; testosterone: 3.2 ng/mL; estradiol: 18 pg/mL). After 2 years of glucocorticoid administration, the clinical pregnancy of his wife was established by using in vitro fertilization (IVF), resulting in the delivery of a female offspring (3650 g) who was confirmed as negative for CAH by serum 17‐OHP and 21‐deoxycortisol measurement.\"}", "questions": ["What glucocorticoid treatment strategy (including dosage category) was started for the patient with congenital adrenal hyperplasia?", "After six months of glucocorticoid therapy, what changes were noted in the patient's hormonal levels (FSH, LH, testosterone, estradiol) and hemoglobin?"], "ground_truth_arguments": ["After 6 months of low‐dose , daily oral glucocorticoid therapy ( 0.5 mg / d ) , the serum FSH , LH , testosterone , and estradiol levels returned to normal levels ( 9.2 IU / mL , 1.8 IU / mL , 0.8 ng / mL , and < 10 pg / mL , respectively ) . The polycythemia also improved to a Hb level of 15.2 g / dL.", "a low‐dose , oral glucocorticoid of 0.5 mg / d was started under the diagnosis of CAH"]}
{"id": "CaseReportBench:train-126", "dataset": "CaseReportBench", "role": "Vitals-and-Hematology", "document": "{'Case Report': 'Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made. Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years. There was no other significant positive clinical findings. Case three was a 14-year-old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia. Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth. On examination, he had molluscum contagiosum lesions on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case. Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis. Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern. The features of all these five cases have been summarized in Table 1 .'}", "questions": ["What did the peripheral blood smear reveal about red blood cell morphology and white blood cell abnormalities?"], "ground_truth_arguments": ["Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia"]}
{"id": "CaseReportBench:train-82", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case report': 'An 11-year-old male had presented to the hospital with a history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4-5 years. There was no history of fever or localized pain. On examination, the blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg (75th-90th centile) and his height measured 138 cm (50th centile). Generalized skin hyperpigmentation was present. Systemic examinations were normal. Local examination revealed bilateral scrotal swelling with normal-appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia (testis length 3.5 cm, penile length 10 cm) and stage 3 for pubic hair. The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size (right and left testicular volume – 2.9 mL and 2.8 mL respectively) with multiple well-defined round to oval hetero-echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B). On screening abdominal sonography, a large well-defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity ( Figs. 3 A and B). Based on these findings, the possibility of testicular malignancy with adrenal metastasis was considered. Contrast-enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands (left>right) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C). Serum tumor markers (alpha-fetoprotein, LDH, and Beta hCG) were negative hence, the diagnosis was reconsidered for the possibility of testicular adrenal rest tumors in an undiagnosed case of congenital adrenal hyperplasia. Fig. 1 (A) Grayscale US of scrotum showing normal-sized right testis with heterogeneous appearance. (B) US image of bilateral testes with multiple nodules containing tiny calcific foci (black arrow). Fig 1 Fig. 2 (A) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. (B) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 (A) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions (white arrow). (B) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions (white arrow). Fig 3 Fig. 4 (A) Contrast enhanced computed tomography (CECT) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia (White arrows). (B) CECT pelvis axial section showing multiple enhancing nodules in the right testis (black arrow). (C) CECT pelvis axial section showing multiple enhancing nodules in left testis (black arrow). Fig 4 X-ray left wrist AP/lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq/L (normal range: 3.5-4.5 mEq/L), whereas the sodium level remained within normal limits at 140 mEq/L. There was a significantly heightened level of 17-hydroxyprogesterone at 1800 ng/dL (normal range: <110 ng/dL), accompanied by normal levels of lactate dehydrogenase (LDH), beta-human chorionic gonadotropin hormone (B-HCG), and alpha-fetoprotein (AFP). Additionally, the serum adrenocorticotropic hormone (ACTH) concentration was elevated, measuring 564 pg/mL (normal range: 7.2-63.3 pg/mL), while cortisol levels were diminished, measuring 5.7 µg/dL (normal range: 7-25 µg/dL). Dehydroepiandrosterone sulfate (DHEA-S) was measured at 5.25 µmol/L (normal range: ≤ 3.726 µmol/L), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng/dL (normal range: 31-65 ng/dL), and there was a reduced level of Inhibin B, measuring 71.1 pg/mL (normal range: 240-445 pg/mL). Collectively, these findings point towards a diagnosis of congenital adrenal hyperplasia. The patient is currently undergoing treatment with hydrocortisone and is on regular follow-up. The 3-month follow-up revealed clinical improvement with a reduction in testis size and decreased ACTH levels, indicating positive progress. Fig. 5 X-ray of left wrist AP and a lateral view showing accelerated bone age corresponding to approximately 18 years. Fig 5', 'Patient consent': 'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.'}", "questions": ["What physical examination findings were noted regarding the scrotum, testes, and Tanner stage of genital and pubic hair development?", "What ultrasound characteristics of both testes were observed, including size, echogenicity, presence of nodules or calcifications, and Doppler vascularity?", "What did contrast-enhanced CT of the pelvis demonstrate about the testes, particularly regarding density and enhancing nodules?", "Were the patient's serum potassium and sodium concentrations within normal limits, and if abnormal, how were they described?"], "ground_truth_arguments": ["bilateral scrotal enlargement", "bilateral scrotal swelling with normal - appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia ( testis length 3.5 cm, penile length 10 cm ) and stage 3 for pubic hair", "Bilateral testis was normal in size ( right and left testicular volume – 2.9 mL and 2.8 mL respectively ) with multiple well - defined round to oval hetero - echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity", "Bilateral testes appeared hypodense with multiple enhancing nodules within", "Grayscale US of scrotum showing normal - sized right testis with heterogeneous appearance. ( B ) US image of bilateral testes with multiple nodules containing tiny calcific foci ( black arrow ). Fig 1 Fig. 2 ( A ) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. ( B ) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity", "CECT pelvis axial section showing multiple enhancing nodules in the right testis ( black arrow ). ( C ) CECT pelvis axial section showing multiple enhancing nodules in left testis", "serum potassium concentration was found to be elevated at 5.8 mEq / L ( normal range : 3.5 - 4.5 mEq / L ), whereas the sodium level remained within normal limits at 140 mEq / L."]}
{"id": "CaseReportBench:train-300", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': \"A 23 year-old female patient, 160 cm tall and 48 kg, was diagnosed with acute appendicitis and admitted for a laparoscopic appendectomy. She had no abnormalities in her pediatric medical history, but from the age 18, she had slowly begun experiencing headaches in her left temporal lobe, nausea, and vomiting. In June of that year, she experienced generalized convulsions and aphasia. In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered (7.54 mM/L). The patient was suspected to have MELAS syndrome. She was diagnosed with MELAS after testing (adenosine-to-guanine transition at t-RNA nucleotide 3243 in PCR sequencing). After she turned 21, she was diagnosed with Type I DM. The patient had to orally ingest 200 mg of carbamazepine and 100 mg of aspirin per day and subcutaneously inject 30 units of insulin in the morning and 20 units in the evening. She had no history of total anesthesia. In a physical examination before the anesthesia, the patient was able to read but had auditory aphasia such that she could not understand spoken words. In the physical examination, there were no signs of hypotonia or amyotrophy of the limbs. The laboratory results showed hyponatremia (126 mEq/L), hyperglycemia (257 mg/dl), and light metabolic acidosis (pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM/L, BE -5.3 mM/L). There were no abnormal findings in the chest X-ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67% and no abnormal findings. For sugar control, 4 units of shortacting insulin were injected, and 0.9% normal saline was administered to control hyponatremia. No other pre-operative measures were performed. After the patient was taken to the operating room, we attached ECG standard leads II, noninvasive monitors for blood pressure, heart rate, arterial oxygen saturation, capnogram, and bispectral index (BIS), and a nerve stimulator to the patient using the Multi Channel Anesthesia Monitor S/5™ (Datex-Ohmeda, USA). Preliminary vital signs were as follows: blood pressure 115/65 mmHg, heart rate 100 beats/min, oxygen saturation rate 97%, and the ECG results appeared normal. The patient underwent 3 minutes of denitrogenation with 100% oxygen through a face mask. Afterwards, we administered lidocaine (40 mg) with the Master TCI (Fresenius Vial S.A., France); we then injected 2% propofol (Fresofol®, Fresenius Kabi, Austria) and remifentanil (Ultiva™, GlaxoSmithKline, UK) at target concentrations of 4 µg/ml (Marsh-model) and 5 ng/ml (Minto-model), respectively. After roughly 90 seconds had passed, we checked lid reflexes and found that the patient had lost consciousness. We administered atracurium (0.5 mg/kg), the BIS was 50, and we saw that there was no response to TOF stimulation with the nerve stimulator placed on the ulnar nerve. Endotracheal intubation was then performed without complications. We started mechanical respiration with air (1.5 L/min), oxygen (1.5 L/min), respiratory volume of 450 ml, and respiratory rate of 12 breaths per minute. To control ventilation, the capnogram was kept at 35-40 mmHg. We used spirometry to measure the respiratory volume and pulmonary compliance. We started invasive blood pressure monitoring through the radial artery and measured the esophageal temperature with a body temperature monitor. During the operation, we used a forced-air warming blanket (Bair Hugger™, Austine Medical, USA) to stabilize the patient's body temperature. For fluid maintenance, we administered 0.9% normal saline at 200 ml per hour. During the operation, the patient's vitals were kept stable with blood pressure at 120-140/60-80 mmHg, heart rate 80-100 beats/min, oxygen saturation 100%, body temperature 37.0-37.4℃, and BIS 40-60. Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM/L, BE -2.1 mM/L; her electrolytes were Na + 125 mEq/L, K + 3.8 mEq/L, Cl - 88 mEq/L; and her blood sugar was 176 mg/dl. Twenty minutes prior to the end of the operation, we administered ondansetron (4 mg) to prevent post-operative nausea and vomiting. After suturing the peritoneum, we stopped injecting remifentanil, kept the level of propofol in the target effect site at 2 µg/ml, and restored spontaneous breathing. After the operation was over, we stopped injecting propofol and stabilized spontaneous breathing at 300 ml per breath on the spirometer. On the nerve stimulator, the TOF rate was kept at 0.95. To reverse the muscle relaxant effects, we administered glycopyrrolate (0.4 mg) and pyridostigmine (15 mg). Afterwards, the patient responded to voice commands and opened her eyes. With stabilized spontaneous breathing, she was extubated. The operation lasted around 1 hour, and during the operation, 350 ml of 0.9% normal saline were used. We then moved the patient to the recovery room and kept her under observation with blood pressure, electrogram, and oxygen saturation monitors. In the recovery room, we gave her oxygen at 5 L/min through the facial mask. The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM/L, and BE -3.6 mM/L; her electrolyte levels were Na + 128 mEq/L, K + 4.1 mEq/L, and Cl - 90 mEq/L; and her blood sugar level was 120 mg/dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM/L. Three days after the operation, the patient showed no complications from the operation or anesthesia, so she was released from the hospital.\"}", "questions": ["What is the typical age range when patients first begin experiencing these symptoms?"], "ground_truth_arguments": ["age 18"]}
{"id": "CaseReportBench:train-378", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}", "questions": ["Describe the patient’s long‑standing intellectual disability, educational background, and current functional abilities such as conversation and ability to perform household tasks.", "Detail the psychiatric and behavioral changes observed in the past three months, including delusions, mood or affect, response speed, speech reduction, eating difficulty, incontinence, weight loss, and any other abnormal behaviors.", "Summarize the cerebral MRI findings, specifying white‑matter demyelination, signal‑intensity changes, and the presence and degree of cerebral atrophy.", "List the findings of the neurological examination, mentioning cervical rigidity, Kernig sign, deep‑tendon reflexes, limb muscle strength, and Babinski response.", "Provide evidence of peripheral neuropathy, including results of electrophysiological studies of the upper and lower limbs and any related imaging observations.", "Report the electroencephalogram findings, focusing on abnormal activity patterns such as increased slow waves or diffuse slowing.", "State the cerebrospinal fluid analysis results, particularly the protein concentration compared with normal reference ranges."], "ground_truth_arguments": ["history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework", "psychiatric signs", "Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy", "poor mental state", "Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative", "psychiatric and behavioral disturbances, cognitive decline", "peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI.", "The electroencephalogram ( EEG ) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy", "Cerebrospinal fluid protein was mildly elevated : 680.4 mg / L ( normal range : 150 - 400 mg / L", "he showed progressive delusion ( he believed unreasonably that he had a serious disease and was going to die ), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence,"]}
{"id": "CaseReportBench:train-418", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What are the patient’s demographic details and the general characteristics of the tremor symptoms that prompted referral?", "What is known about the health status and consanguinity level of the patient’s parents?", "When was the patient first diagnosed with congenital adrenal hyperplasia, and what clinical features suggested the diagnosis?", "When was hypertension first identified in the patient, and what management was started?", "How many adrenal crises has the patient had, at what stages of life did they occur, and what triggers were noted?"], "ground_truth_arguments": ["A 15 - yr - old male patient was referred to our department with a one - year history of gradual worsening of tremors.", "healthy, second - degree consanguineous parents", "He was diagnosed, at 40 d old, with salt - wasting 21 - hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome", "hypertension at 8 yr of age", "Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses"]}
{"id": "CaseReportBench:train-352", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'The patient is a 45y Caucasian male, height 182cm, weight 80kg, with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y. At age 27y he had undergone muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets. Electroneurography at age 27y revealed axonal polyneuropathy. 24h-ECG at age 30y disclosed an intermittent AV-block II and electroencephalography generalized poly-spike waves in the absence of seizures. Clinical neurologic investigation at age 40y revealed, in addition to the above mentioned abnormalities, bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes. Cerebrospinal fluid (CSF) investigations at age 40y revealed elevated protein (1008mg/l, n: 150-450mg/l) exclusively. Needle-(electromyography) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations. A Guillain-Barre-syndrome (GBS) was suspected and immunoglobulins administered with a beneficial effect. Transthoracic echocardiography at age 40y revealed mild myocardial thickening. At late age 40y mild weakness of the lower limbs (M5-/M4+) and an abnormal respiratory pattern were noted for the first time. Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm. Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol/l after 8 minutes. Upon supra-maximal stimulation of the phrenic nerve at age 41y no answer could be evoked and needle-EMG of the rectus abdominis muscle revealed abnormal spontaneous activity. Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged-red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX-negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH-CoQ-oxidoreductase was 7.4 U/g NCP (n, 15.8-42.84 U/g NCP) and the activity of the cytochrome-c-oxidase 89 U/g NCP (n, 112-351 U/g NCP). Investigation for mtDNA deletions or insertions by long-range PCR was normal. Southern blot could not be carried out because of insufficient material. nDNA located genes responsible for mitochondrial myopathy were not tested. The family history was positive for diabetes (grandmother from the mother’s side) and cardiac abnormalities (mother). At age 45y he was admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles (Table 2 ). There was no indication for heart failure. Though he was awake with normal oxygenation, he required intubation and mechanical ventilation because of hypercapnia due to muscular respiratory insufficiency. Clinical neurologic examination revealed ptosis, ophthalmoparesis, weak head anteflexion and retroflexion (M5-), weakness of the upper limbs with distal predominance (M4 to M5-), proximal weakness of the lower limbs (M5-) absent tendon reflexes, generalized wasting, and stocking-type sensory disturbances. Blood tests revealed hyponatriemia (129mmol/l, n: 135-150mmol/l) and slight anemia (Table 1 ). The diaphragm was moving normally. Cerebral CT was normal. Under controlled ventilation elevated CO 2 decreased to near normal values within 3 days (Table 2 ). On hospital day (hd) 3 he was extubated but respiratory insufficiency with hypercapnia recurred, why he required re-intubation and ventilatory support on hd5 (Table 2 ). One day after re-intubation, tracheostomy was carried out. Blood gases normalized (Table 2 ) and from hd8 ventilatory support could be discontinued during daytime. Since a GBS was additionally suspected upon the history and the elevated CSF-protein, immunoglobulins were given. Under this regimen respiratory function further improved and he was able to sit with support during daytime. Unsupported sitting was impossible due to affected truncal muscles.', 'Case Report:': 'A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation.'}", "questions": ["What histopathological abnormalities were observed in the left deltoid muscle biopsy (e.g., myopathic lesions, glycogen or lipid accumulation)?", "What abnormalities were identified in the cerebrospinal fluid at age 40?", "What cardiac abnormalities were identified on transthoracic echocardiography at age 40?", "What did the lung radioscopy reveal about diaphragm mobility?", "What was the lactate response observed during the 40 W stress test?", "What were the main histopathological and biochemical findings from the right deltoid muscle biopsy performed at age 41?", "What electrolyte and hematologic abnormalities were observed in the blood tests?", "What were the findings of the cerebral CT scan?", "How did arterial blood gases change after ventilatory support (e.g., normalization of CO₂ levels)?"], "ground_truth_arguments": ["muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets", "Cerebrospinal fluid ( CSF ) investigations at age 40y revealed elevated protein ( 1008mg / l, n : 150 - 450mg / l ) exclusively", "Transthoracic echocardiography at age 40y revealed mild myocardial thickening", "Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm", "Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol / l after 8 minutes", "Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged - red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX - negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH - CoQ - oxidoreductase was 7.4 U / g NCP ( n, 15.8 - 42.84 U / g NCP ) and the activity of the cytochrome - c - oxidase 89 U / g NCP ( n, 112 - 351 U / g NCP ). Investigation for mtDNA deletions or insertions by long - range PCR was normal.", "Blood tests revealed hyponatriemia ( 129mmol / l, n : 135 - 150mmol / l ) and slight anemia", "Cerebral CT was normal.", "Blood gases normalized", "elevated CSF - protein", "Biochemical investigations revealed a combined complex I+IV defect"]}
{"id": "CaseReportBench:train-225", "dataset": "CaseReportBench", "role": "Pregnancy", "document": "{'Diagnoses:': 'Ultimately, the patient was diagnosed with argininemia with homozygous mutation (c.32T>C) of the ARG1 gene at 10 years old. Blood tests showed mildly elevated blood ammonia and creatine kinase, and persistently elevated bilirubin.', 'Case report': \"The patient was born at 36 +4 weeks’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness. At this time, his height and weight were 86 cm and 12.5 kg, respectively (both were below the 3rd percentile, according to China's 1995 urban 0–18 year-old male height percentiles scale). A neurologic examination focusing on the motor and sensory nervous system and cerebellar function produced unremarkable findings. Laboratory tests revealed retardation of bone age (equivalent to a 1 year old) and mildly elevated total bilirubin (29.4 μmol/L, normal range: 2–24 μmol/L), direct bilirubin (10.4 μmol/L, normal range: 0–7 μmol/L), and indirect bilirubin levels (18.6 μmol/L, normal range: 1.7–17 μmol/L) but normal hepatic enzyme levels. Blood glucose was slightly lower than normal (3.52 mmol/L, normal range: 3.9–6), whereas his electrolytes were normal. Screening tests for hepatitis B and A were negative. A growth hormone excitement test revealed low levels of growth hormone (0 minute: 0.76 ng/mL; 30 minutes: 4.5 ng/mL; 60 minutes: 6.3 ng/mL; 90 minutes: 4.1 ng/mL; and 120 minutes: 1.5 ng/mL). An MRI revealed a normal pituitary gland, and thyroid function was normal. The boy was diagnosed with PGHD and managed accordingly, being treated with growth hormone for about 1 month. No treatment effect was evident. However, he received no follow-up until 10 years of age. At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance. At this time, his height and weight were still below the 3rd percentile, at 116 cm and 20.1 kg, respectively. He exhibited no organomegaly. His muscle strength of the low extremities was grade 4 (Oxford Scale), and he showed increased distal muscle tone than normal, hyper-reflexia, and a negative Babinski sign. Laboratory tests revealed mildly elevated hepatic enzyme levels, including aspartate transaminase (50.9 IU/L, normal range: 0–50 IU/L) and alanine transaminase (52 IU/L, normal range: 0–45 IU/L), as well as mildly elevated total bilirubin (47.7 μmol/L, normal range: 0–25 μmol/L), direct bilirubin (16.4 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (31.3 μmol/L, normal range: 0–25 μmol/L). His creatine kinase (564.4 IU/L, normal range: 55–190 IU/L) and blood ammonia levels (62.3 mmol/L, normal range: 9–30 mmol/L) were slightly elevated. A urine occult blood test was positive (++). Red blood cells (3–4/HP, normal range: 0–3/HP) were evident in a urine sediment microscopy. Both renal ultrasound and renal function were normal, as were the results of cranial MRI and electroencephalography. A peripheral nerve examination revealed reduced compound muscle action potential (CMAP) of the right peroneal nerve and bilateral tibial nerve, while the right peroneal nerve distal latency was suspected to be prolonged. A muscle biopsy revealed neurogenic lesion (Fig. 1 ). A gene test was performed and the results demonstrated that he carried compound homozygote mutations of ARG1 (c.32T > C) (Fig. 2 ). Lee et al and Wu et al reported the mutation, which can lead to argininemia, in South Korea and Chinese populations in 2011 and 2015. Subsequently, his blood and urine amino acid levels were analyzed, revealing a blood arginine concentration of 108.42 μM (normal range: 10–50 μM) as well as elevated urinary excretion of orotic acid; however, his blood citrulline, glutamine, glutamate, and alanine concentrations were normal. His intelligence quotient was lower than normal, at 80. The boy subsequently diagnosed with argininemia. Following the diagnosis, we recommended that the patient begins a low-protein diet (0.8 g/kg/day) to decrease his blood arginine levels, as well as start taking citrulline (150–200 mg/kg/day). His mental state and vomiting had clearly improved after 3 months of this treatment. Laboratory tests conducted again at a local hospital which the following values were obtained (note that the normal ranges used at this hospital slightly differ from those used at our hospital): aspartate transaminase (45 IU/L, normal range: 0–37 IU/L), alanine transaminase (46.1 IU/L, normal range: 0–40 IU/L), total bilirubin (31.9 μmol/L, normal range: 3.4–20.5 μmol/L), direct bilirubin (14.3 μmol/L, normal range: 0–6.8 μmol/L), and indirect bilirubin levels (17.6 μmol/L, normal range: 0–18 μmol/L). His urine occult blood test was positive (+). No red blood cells were evident in his urine sediment microscopy. After 9 months treatment, his height and weight reached 121 cm and 22 kg, but his spastic diplegia symptoms had not improved.\", 'Patient concerns:': 'A Chinese boy initially presented with severe stunting and partial growth hormone deficiency (PGHD) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later (at 10 years old), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy.'}", "questions": ["What information is provided about the gestational age at delivery and the infant's birth weight?", "What neonatal complications were reported in the first days after birth, and were any hospitalizations required?"], "ground_truth_arguments": ["born at 36 +4 weeks ’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia."]}
{"id": "CaseReportBench:train-507", "dataset": "CaseReportBench", "role": "Musculoskeletal-System", "document": "{'Case Report': 'A 24‐year‐old woman was admitted to our hospital with mildly impaired consciousness and myoclonus in the extremities. She had been diagnosed with MELAS at 21 years of age. Genetic testing revealed a 3271 T>C transition in the MT‐TL1 gene, clinically confirming the diagnosis of MELAS. After admission to hospital, neurological examination showed myoclonic movement in the extremities, mandible, and trunk. Muscle weakness was detected in the upper and lower limbs bilaterally. A laboratory examination showed increased serum pyruvic acid (2.1 mg/dL) and lactate (75 mg/dL). Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging (Fig. 1 ). Antiepileptic drugs levetiracetam, perampanel, lacosamide, and clobazam were initiated. L‐arginine, coenzyme Q10, and L‐carnitine aimed at supporting mitochondrial energy production were given simultaneously. As the impaired consciousness and myoclonus persisted for 2 weeks, we undertook brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex. Electroencephalography revealed high‐amplitude slow and spiked waves. We diagnosed the patient with non‐convulsive status epilepticus. To control the seizures, propofol was given at a dose of 2.7 mg/kg/h for 12 h and then increased to 5.4 mg/kg/h, with midazolam added at a dose of 2 mg/h. On day 5, the urine appeared brown and arterial blood gas revealed metabolic acidosis (pH 7.261, pCO 2 33.0 mmHg, HCO 3 - 14.4 mmol/L, and lactate 99 mg/dL). Creatinine kinase was elevated at 20,999 U/L. The patient was diagnosed with PRIS. She was transferred to the intensive care unit (ICU) on day 19 of hospitalization. On admission to the ICU, the vital signs were as follows: body temperature, 39°C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths/min; and SpO2, 99% (FiO 2 40%). Laboratory findings showed metabolic acidosis (lactic acid, 99 mg/dL; pyruvic acid, 0.92 mg/dL), creatinine kinase 29,560 U/L, and myoglobin 9,845 ng/mL. We treated her with interruption of propofol and continuous hemodiafiltration for metabolic acidosis. We continued coenzyme Q10, L‐carnitine, and L‐arginine for mitochondrial support for MELAS and antiepileptic drugs including levetiracetam, perampanel, lacosamide, and clobazam. After concurrent treatment of PRIS and MELAS, metabolic acidosis and creatinine kinase gradually decreased after reaching 59,000 IU/L on day 2 of ICU admission. Continuous hemodiafiltration was discontinued on day 11. Tracheostomy was carried out because i.v. midazolam treatment was prolonged to control the status epilepticus. Mechanical ventilation was discontinued on day 25 (Fig. 2 ). After rehabilitation, the patient was discharged on foot.', 'Case Presentation': 'A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus. To control the non‐convulsive status epilepticus, propofol was administered. Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated. The patient was diagnosed with PRIS. We treated her with interruption of propofol. She required mechanical ventilation for 25 days. After rehabilitation, she recovered and was discharged.'}", "questions": ["What neuromuscular abnormalities were identified in the patient's upper and lower limbs during the initial examination?", "What alteration in urine appearance was reported during the patient's intensive care stay?", "What specific syndrome was diagnosed when the patient developed metabolic acidosis and markedly elevated creatine kinase while on propofol?"], "ground_truth_arguments": ["Muscle weakness was detected in the upper and lower limbs bilaterally", "urine appeared brown", "PRIS"]}
{"id": "CaseReportBench:train-615", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'CASE REPORT': \"A 33-year-old G2P1 woman presented to our obstetric unit at 17 weeks' gestation for antenatal care of her second pregnancy. Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median (MoM) with low alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) level, 0.6 MoM and 0.52 MoM, respectively, which were interpreted as a high risk of Edward syndrome (1 : 79) and Smith-Lemli-Opitz (SLO) syndrome (1 : 7). 8, 9 The karyotype by amniocentesis was 46,XX. Level II ultrasonography after 21 weeks' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia. Upon reevaluation of family history, however, the parents revealed that their 27-month-old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36+2 weeks' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia (125 mEq/L) and hyperkalemia (6.6 mEq/L). Basal adrenal hormone levels and an adrenocoticotropic hormone (ACTH) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography (CT) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C>T in exon 7 of StAR . She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose. Therefore, prenatal testing was performed in the second sibling for the relevant disease-causing mutation from fetal cells by amniocentesis. Exon 7 and its adjacent intronic sequences were amplified by PCR, using forward primer 5'-CCTGGCAGCCTGTTTGTGATAG-3' and reverse primer 5'-ATGAGCGTGTGTACCAGTGCAG-3', which revealed a homozygous c.772C>T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 ). A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks' gestation. At birth, the baby presented with normal female external genitalia. Screening for congenital adrenal hyperplasia was normal, 17α-OH progesterone (17α-OHP) 8.33 ng/mL (normal 1.7-25.0 ng/mL). There were no clinical signs or symptoms until 3 months after birth. Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination. Her laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography ( Table 1 ). Genetic evaluation from the peripheral blood confirmed the same mutation. She was diagnosed with CLAH and discharged on the 9th day of hospitalization after treatment of mineralocorticoid and hydrocortisone.\"}", "questions": ["What types of hormone replacement therapies were used in the patients' treatment?"], "ground_truth_arguments": ["treatment of mineralocorticoid and hydrocortisone ."]}
{"id": "CaseReportBench:train-482", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}", "questions": ["What neonatal or early infant health conditions are documented in the patient's medical history?"], "ground_truth_arguments": ["no history of neonatal jaundice or chronic infantile diarrhea"]}
{"id": "CaseReportBench:train-586", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["Which endocrine laboratory tests are mentioned in the case, and how are their results described (e.g., normal, elevated, decreased)?", "How many 17‑OH progesterone measurements are reported, and in what clinical situations were they obtained?", "Which investigations were performed to evaluate secondary hypertension, and what were the findings that led to the diagnosis of essential hypertension?", "What abnormalities were observed on brain MRI, including signal characteristics, lesion location, presence of cortical‑subcortical atrophy, and the status of the corpus callosum?", "What were the results of the extensive laboratory work‑up, covering routine blood and urine tests, liver function, lactate, amino acids, ceruloplasmin, inflammatory markers, urine organic acids, CSF analysis, Arylsulfatase A activity, and autoantibody screens?"], "ground_truth_arguments": ["17 - OH progesterone level of 215 ng / ml,", "Detailed investigations ( renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11 - Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia ) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made", "basal level of 17 - OH progesterone at 12 ng / ml, ACTH of 77 pg / ml ( reference range : 10–50 pg / ml ) and androstenedione of 2.12 nmol / l ( reference range : 0.77–1.82 nmol / l )", "Brain MRI showed bilateral periventricular white matter hyperintensity on T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2 - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) and cortico - subcortical atrophy. Fig. 2 FLAIR - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1 - weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico - subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 )", "Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative."]}
{"id": "CaseReportBench:train-327", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Patient 2': 'The elder sister of patient 1 was an 84-year-old woman with a stooping posture presenting with tremors since the age of 60. In her 70s she started walking with the aid of a walking stick. At 82 years of age, she was hospitalized for generalized seizures and disturbed consciousness. CT of T10 revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 e). Brain MRI revealed hyperintense lesions around the white matter (Fig. 2 f); elevated serum and CSF lactate levels were also noted at this time. The mitochondrial DNA analysis of the lymphocytes did not indicate MELAS (m.3243A>G) or MERRF (m.8344A>G) mutations. The patient’s condition remained undiagnosed and she died at the age of 84. CK levels in all her four sons were found to be elevated and her third son was diagnosed with epilepsy. She and her fourth son had also been previously diagnosed with Hashimoto thyroiditis (Fig. 1 ). Patient 1 was examined using pathological, biochemical, and genetic analyses. The Institutional Review Board of Kagoshima University approved this study. Patient 1 gave the written and informed consent for her participation in this study.', 'Histochemical and immunohistochemical studies': 'Frozen biopsies of the biceps brachii muscle specimens were obtained from patient 1. The specimens were sliced into 8 μm sections and placed on aminosilane-coated slides. Histochemical and immunohistochemical procedures were performed as previously described.', 'Histological and immunohistochemical characterizations': 'The muscle fibers ranged from 10 to 80 μm in diameter. Sixty-nine of the 609 Gomori trichrome stained muscle fibers (11.3%) were ragged-red fibers (Fig. 3 a). Cytochrome c oxidase (COX) activity was deficient in many of the ragged-blue fibers that were stained with succinate dehydrogenase (SDH) and COX (233 of 881 muscle fibers, 26.4%) (Fig. 3 b, c), and no blood vessels showing strong SDH reactivity were observed. In NADH dehydrogenase-reactive sections, focal decreases and increases in oxidative enzyme activities were observed. Adenosine monophosphate (AMP) deaminase activity was normal. The random checkerboard distribution of the histochemical fiber types was preserved as shown in the ATPase-reactive sections. Acid phosphatase activity was slightly high in some fibers. Muscle fiber glycogen contents appeared normal and the lipid contents were slightly high in some fibers. Electron microscopy showed abnormal proliferation of mitochondria with paracrystalline inclusions (Fig. 4 ). Fig. 3 Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged-red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged-blue fibers with COX deficiency. a−c Bar 100 μm Fig. 4 Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions that are suggestive of mitochondrial myopathy are shown. a bar 1 μm, b bar 500 nm', 'Mitochondrial DNA analysis': 'In case of patient 1, the total DNA was extracted from the peripheral blood leukocytes and the frozen muscle specimens using the DNeasy Blood & Tissue kit (Qiagen). MitoChip v2.0 (The GeneChip ® Human Mitochondrial Resequencing Array 2.0), which provides a standard assay for the complete sequence analysis of human mitochondrial DNA, was obtained from Affymetrix. The patient’s entire mitochondrial DNA was sequenced using MitoChip v2.0 as previously described. Analysis of the microarray data obtained with MitoChip v2.0 was performed using GeneChip Sequence Analysis Software v4.0 (Affymetrix). In order to reveal the mutations that were confirmed by MitoChip v2.0, a 465-base pair PCR product that spanned all of the mutation sites was screened by DNA sequencing. In brief, 50 ng of the patient’s genomic DNA was amplified using the hot-start PCR method and a forward (5′-CACCATTCTCCGTGAAATCA-3′) and reverse primer (5′-AGGCTAAGCGTTTTGAGCTG-3′). Each PCR product was generated under the following conditions: 15 min at 95°C, 42 cycles of amplification (95°C for 30 s, 61°C for 30 s, and 72°C for 1 min), and 30 min at 72°C. Using a presequencing kit (USB, Cleveland, OH, USA), the patient’s PCR products with abnormal elution profiles were purified, and the appropriate PCR products from relatives and control chromosomes were obtained and sequenced by dye-terminator chemistry using an ABI Prism 377 sequencer (Applied Biosystems, Foster City, CA, USA). The resulting sequences were then aligned and any mutations were evaluated using the Sequencher sequence alignment program (Gene Codes, Ann Arbor, MI, USA). The polymorphic and pathogenic natures of the confirmed mutations were checked against two databases: the MITOMAP ( http://www.mitomap.org/ ) and GiiB-JST mtSNP database ( http://mtsnp.tmig.or.jp/mtsnp/index.shtml ). Using MitoChip v2.0, 37 missense variants were detected in the mitochondrial DNA of the peripheral blood lymphocytes. All of these variants show polymorphisms and are listed in the MITOMAP and GiiB-JST mtSNP databases. Two additional missense variants were detected in the mitochondrial DNA of the muscle homogenate; the variants were m.602C>T in the tRNA Phe gene and m.16111C>G in the D-loop. The variant m.16111C>G is listed as a polymorphism, but the variant m.602C>T is not reported in either database. The m.602C>T variant was also confirmed by direct sequencing. The sequence chromatogram showed a heteroplasmic m.602C>T transition in the muscle homogenate mitochondrial tRNA Phe gene (Fig. 5 a). The proportion of mutant mitochondrial DNA in the muscle was 64.7 ± 1.2% (mean ± SD; the operation was performed thrice). Mutant mitochondrial DNA was not detected in the blood lymphocytes when measured using real-time amplification refractory mutation system quantitative PCR analysis (RT-ARMS qPCR), as previously described. Healthy Japanese controls ( n = 100) did not show these mutations in their blood lymphocytes, at least not within the limits of Sanger’s method for DNA sequencing. Fig. 5 a Sequence chromatogram of the mitochondrial DNA region that encompasses the m.602C>T alteration ( asterisk ) that was obtained from the skeletal muscle of patient 1 (reverse complement). b Schematic diagram of the mitochondrial tRNA Phe cloverleaf structure showing previously reported mutations and the m.602C>T alteration in the D-stem. c Comparison of mitochondrial tRNA Phe from different species. Base pairs, including the 602 nucleotides, are shown in boxes', 'Patient 1': 'A 73-year-old woman (Fig. 1, III-8) presenting with abnormal posture and gait disturbance. Since the age of 63, the patient had a slight stooping posture and a pushed-out waist. At 68 years of age, she started using a walking stick because of her unstable gait. She was diagnosed with hypothyroidism by her family physician and administrated with 25 μg/day levothyroxine; however, her symptoms did not improve. At 70 years of age, it gradually became more difficult for her to climb the stairs. At 71 years of age, she was admitted to another hospital. Doctors suspected myopathy because of elevated serum CK levels. She visited our hospital presenting with prominent paraspinal muscle atrophy and mild proximal weakness of limbs. Hypothyroidism-related myopathy was suspected in her, and hence, the levothyroxine dose was increased to 50 μg/day; however, her symptoms did not improve. She had a family history of bent spine, i.e., in her elder sister (patient 2, Fig. 1, III-5), mother (Fig. 1, II-3), and maternal aunt (Fig. 1, II-4). Physical examination on arrival revealed a marked atrophy of the paraspinal muscles and abnormal posture (Fig. 2 a, b). She also presented with right ptosis, dysarthria, bilateral cataracts, and hearing loss. Her eye movements were normal. But there was moderate weakness of the neck flexion and mild weakness of the proximal limb muscles. Tendon reflexes were symmetrical, and Babinski’s sign was absent. She had poor balance with tandem gait without limb ataxia. Sensory systems were intact and Romberg’s sign was negative. She scored poorly on the attention and calculation tests that are a part of the Mini-Mental State Examination (score: 25 points). Fig. 1 Pedigree of the family. The arrow indicates the proband. The affected individuals are represented by the solid black symbols ; open symbols represent healthy individuals. Gray symbols indicate individuals with elevated CK levels Fig. 2 a The full-length figure indicates the posture of patient 1 showing her pushed-out waist. b The dorsal view shows the marked atrophy of the paraspinal muscles in patient 1. CT of T10 of c patient 1 (age 71), e patient 2 (age 82), and g a healthy female (age 74) reveals the profound atrophy of the paraspinal muscles in c patient 1 and e patient 2, but not in g the healthy female. Brain MRI studies revealed several differences between the patients 1 and 2. d Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter Laboratory data were as follows: serum CK level was 290 IU/l (normal range 45–163 IU/l), resting blood and cerebrospinal fluid (CSF) lactate levels were normal, thyroid-stimulating hormone levels were slightly low at 0.47 μIU/ml (normal range 0.5–5.0 μIU/ml). Under the administration of 50 μg/day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U/ml (normal range <0.3 U/ml), antithyroid peroxidase antibody levels were high at 46.5 U/ml (normal range <0.3 U/ml), rheumatoid factor levels were high at 152.3 IU/ml (normal value <15.0 IU/ml), antinuclear antibody levels were mildly elevated (titer of 1:80). Autoimmune analyses, including anti-Jo-1, anti-RNP, anti-SS-A, and anti-SS-B, were negative. The oral glucose tolerance test (75 g) was within normal limits, but Holter monitoring revealed high-frequency premature contractions. Pure-tone audiometry indicated sensorineural and high-frequency hearing loss. Needle electromyographic findings of the biceps brachii and rectus femoris muscles indicated mild myopathic features. Computed tomography (CT) of the thoracic spinal nerve 10 (T10) revealed severe atrophy and fatty degeneration of the paraspinal muscles (Fig. 2 c). Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery imaging showed moderate cerebellar and temporo-parieto-occipital lobe atrophy (Fig. 2 d). MR spectroscopy revealed the absence of increased lactate peaks. 123I-IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions.', 'Biochemical studies': 'Enzyme activity levels, blue native polyacrylamide gel electrophoresis (BN-PAGE), and other biochemical measurements of the frozen muscle specimens from patient 1 were performed as previously described. All respiratory chain enzyme activities, which are expressed as a percentage of the normal control values relative to the citrate synthase activity, were greater than 20% (Table 1 ). BN-PAGE revealed no abnormalities in either the respiratory chain complexes or their molecular assembly structures. Table 1 Enzymatic activities for mitochondrial respiratory complexes in patient 1 CI activity (CI/CS) CII activity (CII/CS) CIII activity (CIII/CS) CIV activity (CIV/CS) CS activity Patient 1 0.1938 (0.7027) 0.2723 (0.9874) 1.2737 (4.6192) 0.0579 (0.21) 0.2757 Control 0.3194 (1.6183) 0.2751 (1.3444) 1.3132 (6.5512) 0.0826 (0.3840) 0.2151 Patient 1/control ratio 60.7% (43.4%) 98.9% (73.4%) 97.0% (70.5%) 70.1% (54.7%) Enzymatic activities for individual mitochondrial respiratory complexes are given in nmol/min protein, and represent percentage of normal control ( n = 10) mean relative to a reference enzyme of citrate synthase (CS) The activities are relatively low in complex I and complex IV compared with other complexes CI complex I, CII complex II, CIII complex III, CIV complex IV'}", "questions": ["For each patient, describe the thoracic spine CT findings at the T10 level, specifying presence and extent of paraspinal muscle atrophy and fatty degeneration.", "Summarize the brain MRI/FLAIR findings for patient 1 and patient 2, noting cerebellar, cortical, and white‑matter abnormalities.", "Report the serum and cerebrospinal fluid lactate concentrations for patient 1 and patient 2, indicating whether each is normal or elevated.", "List the thyroid‑stimulating hormone result and the measured autoantibody levels (antithyroglobulin, antithyroid peroxidase, rheumatoid factor, antinuclear antibody) for patient 1.", "State whether patient 1’s serum creatine kinase (CK) level was reported as elevated, and give the absolute value together with the normal reference range.", "Describe the histopathological findings in the biceps brachii muscle of patient 1, including: the number and percentage of ragged‑red fibers; the number and percentage of COX‑deficient (ragged‑blue) fibers; presence or absence of strong SDH reactivity in blood vessels; and observations on NADH dehydrogenase, AMP deaminase, acid phosphatase, glycogen, and lipid staining.", "What ultrastructural mitochondrial abnormalities were observed in patient 1’s muscle by electron microscopy?", "List the mitochondrial DNA variants that were highlighted as noteworthy in patient 1’s muscle tissue, specifying for each: the nucleotide change, the affected gene/region, the heteroplasmy level (if given), and whether the variant is reported as a known polymorphism or a novel/unreported mutation. Indicate whether the variant was also detected in blood lymphocytes.", "Summarize the respiratory chain enzyme activity results for patient 1 relative to citrate synthase, indicating the activity percentages for complexes I‑IV, which complexes showed the lowest activity, and the finding of blue native PAGE regarding complex composition or assembly.", "What were the findings of MR spectroscopy and 123I‑IMP single‑photon emission CT for patient 1?"], "ground_truth_arguments": ["CT of T10 revealed severe atrophy and fatty degeneration of the paraspinal muscles ( Fig. 2 e ). Brain MRI revealed hyperintense lesions around the white matter ( Fig. 2 f ); elevated serum and CSF lactate levels were also noted at this time. The mitochondrial DNA analysis of the lymphocytes did not indicate MELAS ( m.3243A > G ) or MERRF ( m.8344A > G ) mutations", "Sixty - nine of the 609 Gomori trichrome stained muscle fibers ( 11.3 % ) were ragged - red fibers ( Fig. 3 a ). Cytochrome c oxidase ( COX ) activity was deficient in many of the ragged - blue fibers that were stained with succinate dehydrogenase ( SDH ) and COX ( 233 of 881 muscle fibers, 26.4 % ) ( Fig. 3 b, c ), and no blood vessels showing strong SDH reactivity were observed. In NADH dehydrogenase - reactive sections, focal decreases and increases in oxidative enzyme activities were observed. Adenosine monophosphate ( AMP ) deaminase activity was normal. The random checkerboard distribution of the histochemical fiber types was preserved as shown in the ATPase - reactive sections. Acid phosphatase activity was slightly high in some fibers. Muscle fiber glycogen contents appeared normal and the lipid contents were slightly high in some fibers. Electron microscopy showed abnormal proliferation of mitochondria with paracrystalline inclusions ( Fig. 4 ). Fig. 3 Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged - red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged - blue fibers with COX deficiency. a−c Bar 100 μm Fig. 4 Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions", "m.602C > T in the tRNA Phe gene and m.16111C > G in the D - loop. The variant m.16111C > G is listed as a polymorphism, but the variant m.602C > T is not reported in either database. The m.602C > T variant was also confirmed by direct sequencing. The sequence chromatogram showed a heteroplasmic m.602C > T transition in the muscle homogenate mitochondrial tRNA Phe gene ( Fig. 5 a ). The proportion of mutant mitochondrial DNA in the muscle was 64.7 ± 1.2 % ( mean ± SD; the operation was performed thrice ). Mutant mitochondrial DNA was not detected in the blood lymphocytes", "elevated serum CK levels", "Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter Laboratory data were as follows : serum CK level was 290 IU / l ( normal range 45–163 IU / l ), resting blood and cerebrospinal fluid ( CSF ) lactate levels were normal, thyroid - stimulating hormone levels were slightly low at 0.47 μIU / ml ( normal range 0.5–5.0 μIU / ml ). Under the administration of 50 μg / day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U / ml ( normal range < 0.3 U / ml ), antithyroid peroxidase antibody levels were high at 46.5 U / ml ( normal range < 0.3 U / ml ), rheumatoid factor levels were high at 152.3 IU / ml ( normal value < 15.0 IU / ml ), antinuclear antibody levels were mildly elevated ( titer of 1:80 ). Autoimmune analyses, including anti - Jo-1, anti - RNP, anti - SS - A, and anti - SS - B, were negative. The oral glucose tolerance test ( 75 g ) was within normal limits", "Computed tomography ( CT ) of the thoracic spinal nerve 10 ( T10 ) revealed severe atrophy and fatty degeneration of the paraspinal muscles ( Fig. 2 c ). Brain magnetic resonance imaging ( MRI ) with fluid - attenuated inversion recovery imaging showed moderate cerebellar and temporo - parieto - occipital lobe atrophy ( Fig. 2 d ). MR spectroscopy revealed the absence of increased lactate peaks. 123I - IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions. ',", "All respiratory chain enzyme activities, which are expressed as a percentage of the normal control values relative to the citrate synthase activity, were greater than 20 % ( Table 1 ). BN - PAGE revealed no abnormalities in either the respiratory chain complexes or their molecular assembly structures. Table 1 Enzymatic activities for mitochondrial respiratory complexes in patient 1 CI activity ( CI / CS ) CII activity ( CII / CS ) CIII activity ( CIII / CS ) CIV activity ( CIV / CS ) CS activity Patient 1 0.1938 ( 0.7027 ) 0.2723 ( 0.9874 ) 1.2737 ( 4.6192 ) 0.0579 ( 0.21 ) 0.2757 Control 0.3194 ( 1.6183 ) 0.2751 ( 1.3444 ) 1.3132 ( 6.5512 ) 0.0826 ( 0.3840 ) 0.2151 Patient 1 / control ratio 60.7 % ( 43.4 % ) 98.9 % ( 73.4 % ) 97.0 % ( 70.5 % ) 70.1 % ( 54.7 % ) Enzymatic activities for individual mitochondrial respiratory complexes are given in nmol / min protein, and represent percentage of normal control ( n = 10 ) mean relative to a reference enzyme of citrate synthase ( CS ) The activities are relatively low in complex I and complex IV compared with other complexes"]}
{"id": "CaseReportBench:train-361", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What is the patient's age at the time of the current presentation/hospitalization?"], "ground_truth_arguments": ["15 - yr - old"]}
{"id": "CaseReportBench:train-424", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case report': 'We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. The Saudi female patient in the UK developed recurrent bouts of abdominal pain, nausea, and vomiting during first pregnancy, diagnosed as hyperemesis gravidarum, and was treated with IV fluids and antiemetics. There was improvement in the condition and the patient delivered a healthy child (in Saudi). After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatremia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities. She was intubated for 3 days. Initial postextubation, physical examination result was unremarkable except for unexplained behavioral disturbances and lower limb weakness. Initial instigations showed sodium levels ranged between 118–125 mmol/L (135–144 mmol/L), mildly elevated transaminases (aspartate aminotransferase/alanine transaminase), and slight elevation of anti-neutrophil antibodies of the perinuclear type (P-ANCA). Alkaline phosphatase, bilirubin, complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid (CSF) analysis findings were all within normal range. The abdominal imaging result was normal, except for contracted gallbladder and stones. Urine became dark red on exposure to light. Total porphyrins in urine were elevated: 29,100 nmol/24 hours (normal: ≤214), with main elevation in uroporphyrin level, 24,200 nmol/24 hours (normal: ≤30), and mild elevation in coproporphyrin level, 118 nmol/24 hours (normal: ≤38). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene (c. 760delC p.L254X). The patient was treated with intravenous heme arginate (4 mg/kg/day) for 5 days, that was followed by an improvement in the chemical and clinical parameters.'}", "questions": ["Describe the patient’s age, gender, and the initial clinical presentation, including the primary symptoms and signs."], "ground_truth_arguments": ["We present a case of a 26 - year - old female with suspected acute cholecystitis, mental status changes, and seizures"]}
{"id": "CaseReportBench:train-555", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case report': \"A 16-year-old Iraqi boy, born of first-cousin parents, presented to our outpatient clinic at Al-Sadr Teaching Hospital with hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing. He also had hearing loss, speaking difficulties, premature graying of the hair, gynecomastia, corneal arcus, hypospadias, and finger and toe deformities (hallux valgus). These features started at age 10, except for the hypospadias, which was present since birth, and the hearing loss and speaking difficulties, which were diagnosed in early childhood. The mother stated that the child delayed walking until the age of 2 years, and she reported that he had a severe ear infection by the age of 6. The patient has 3 brothers and 2 sisters; his older brother has bilateral swelling of the feet and deformities of the toes, but the patient's other siblings are all healthy. See Table I for clinical examination findings ( Fig 1, Fig 2, Fig 3 ). Table I Findings on examination Examination Findings Vital signs Pulse rate, 83 beats per minute; blood pressure, 100/70 mmHg; respiratory rate, 13 breaths per minute; and temperature, 37°C Anthropometric parameters Weight, 47.1 kg; height, 160 cm; MUAC, 19.3; BMI, 18.4; height/age, -1.7 SD; BMI/age, -0.9 SD Skin Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well-demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees (see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt-and-pepper gray hair (see Fig 2 ) Head OFC, 51 cm (-2.8 SD, <1 st percentile); face looks flat; ears are of abnormal shape and size. Eyes Bilateral corneal arcus; moderate exophthalmos; asymmetrical corneal light reflex. Ophthalmoscopic examination showed bilateral swelling of the optic disc. Visual acuity is normal. Hearing assessment Severe hearing loss Breast Bilateral gynecomastia Heart Normal Abdomen Mild hepatosplenomegaly Lymph nodes Severely enlarged inguinal lymph nodes, with tenderness on palpation Genitourinary Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal. Musculoskeletal Bilateral hallux valgus deformity, with fixed flexion contractures, in the interphalangeal joints of the toes and the little fingers (see Fig 3 ). There is also a nonpitting edema of the ankles. BMI, Body mass index; MUAC, mid-upper arm circumference; OFC, occipitofrontal circumference. Fig 1 Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees. Fig 2 Posterior view of the patient's head shows salt-and-pepper gray hair. Fig 3 Hallux valgus deformity, with flexion contractures of the toes and little fingers. Laboratory test results showed elevated erythrocyte sedimentation rate of 93 (normal range, 0–15 mm/h), elevated serum cortisol of 1030 nmol/L (normal range at morning, 171-536 nmol/L), and decreased serum testosterone level of 2.63 ng/mL (normal range, 2.8-8 ng/mL). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti–double-stranded DNA, anti-cyclic citrullinated peptide, and lipid profile all were normal. Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal, and pure tone audiometry found bilateral profound mixed hearing loss. Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes (see Fig 4 ). The biopsy was taken from the hyperpigmented patch on the medial aspect of the right thigh. Fig 4 Immunohistochemistry stain shows diffuse infiltration of histiocytes. (CD68 + ; original magnification: ×400.)\"}", "questions": ["What aspects of the examination are relevant to identifying congenital genitourinary conditions?", "Describe any notable findings in the external genital region."], "ground_truth_arguments": ["hypospadias", "hypospadias", "Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal"]}
{"id": "CaseReportBench:train-138", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'A 15-yr-old male patient was referred to our department with a one-year history of gradual worsening of tremors. He was born at term, weighing 2,900 g, to healthy, second-degree consanguineous parents. He was diagnosed, at 40 d old, with salt-wasting 21-hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome and a 17-OH progesterone level of 215 ng/ml, and he was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age and responded well to Nifedipine. Detailed investigations (renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11-Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made. During follow-up, he always maintained good adherence to treatment. Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses. The average hydrocortisone dose was 16 mg/m 2 per day, and fludrocortisone was continued at a dose of 100 µg twice daily. Physical findings on the current hospitalization were as follows: height of 158 cm (–1 SD), weight of 85 kg (>2 SD), body mass index (BMI) of 34.13 kg/m 2 (greater than the 97th centile) and blood pressure of 150/80 mmHg. Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline. The results of an ophthalmologic were normal. The results of biochemical investigations were as follow: basal level of 17-OH progesterone at 12 ng/ml, ACTH of 77 pg/ml (reference range: 10–50 pg/ml) and androstenedione of 2.12 nmol/l (reference range: 0.77–1.82 nmol/l). Brain MRI showed bilateral periventricular white matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) and cortico-subcortical atrophy. Fig. 2 FLAIR-weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity (arrow) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1-weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico-subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ). The patient was extensively evaluated. Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative. The diagnosis of brain MRI abnormalities associated with CAH was made. Following administration of propranolol, the tremors decreased moderately.'}", "questions": ["What was the approximate age (in days) at diagnosis for the patient with salt‑wasting 21‑hydroxylase deficiency CAH?"], "ground_truth_arguments": ["40 d old"]}
{"id": "CaseReportBench:train-214", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Cases': 'Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility, accompanied by congenital adrenal hyperplasia ( CAH ). Here are reported two cases of TART s that were referred to Kobe City Medical Center West Hospital for the treatment of infertility and testicular tumors.', 'Case 2': 'A 41 year old man was followed at the local clinic for polycythemia (hemoglobin: 18.0 g/dL; red blood count: 627 × 10 4 ; hematocrit: 53.1%) and hypertension. An abdominal CT scan for the examination of these conditions revealed the enlargement of the bilateral adrenal glands (Figure 5 ). The patient was referred to endocrinologists in the hospital for further investigation. The patient was seen to have obesity (height: 165 cm; weight: 79 kg; Body Mass Index: 29.0 kg/m²). The laboratory tests revealed an extremely high level of ACTH (316.4 pg/mL) and a relatively low level of cortisol (6.8 μg/dL). Although the patient did not have any family history of CAH, the CT findings regarding the adrenal glands, unbalanced pituitary–adrenal hormones, and high level of serum 17‐OHP (62.7 ng/mL) indicated the possibility of CAH. The difference from case 1 is that the first examination was made by endocrinologists, not urologists. The differential diagnosis was made before a testicular examination. The abnormality in the pituitary–gonadal hormonal status (FSH: <0.1 IU/mL; LH: <0.1 IU/mL; testosterone: 10.9 ng/mL; estradiol: 29 pg/mL) indicated the excessive secretion of adrenal androgens. Bilateral testicular tumors were identified in a scrotal ultrasound echo scan and then a urological consultation and several additional examinations were offered in order to rule out a germ cell tumor. At the physical examination, both testes had become slightly atrophied (right: 14 mL; left: 12 mL) (performed with a Prader orchidmeter) and no induration was palpated. All the serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 (Figure 6 A). The semen analysis showed azoospermia. A genetic diagnosis by PCR‐direct sequencing proved CAH due to 21‐hydroxylase deficiency due to CYP21A2 gene mutation. After 6 months of low‐dose, daily oral glucocorticoid therapy (0.5 mg/d), the serum FSH, LH, testosterone, and estradiol levels returned to normal levels (9.2 IU/mL, 1.8 IU/mL, 0.8 ng/mL, and <10 pg/mL, respectively). The polycythemia also improved to a Hb level of 15.2 g/dL. Sperm emerged (concentration: 3.4 × 10 6 /mL; motility: 26%), along with a size reduction in the adrenal hyperplasia and TART (Figure 6 B).', 'Case 1': \"A 41 year old man was referred to Kobe City Medical Center West Hospital, Kobe City, Japan, because of 2 years of infertility. At the physical examination, the patient's physical constitution was as follows (height: 1.58 m; weight: 65 kg; body mass index: 23.9 kg/m²). Both testes had become atrophied (9 mL) (performed with a Prader orchidmeter) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes (Figure 2 A). The semen analysis revealed oligoasthenozoospermia (volume: 2.6 mL; concentration: 7 × 10 6 /mL; motility: 14%). The hormonal examination revealed a normal hormonal status of serum follicle‐stimulating hormone (FSH) of 2.7 mIU/mL, luteinizing hormone (LH) of 1.3 mIU/mL, testosterone of 4.3 ng/mL, and estradiol of 13 pg/mL. All the serum markers for testicular tumors, including human chorionic gonadotropin, alpha‐fetoprotein, and lactate dehydrogenase, were within the normal range. The pelvic magnetic resonance imaging (MRI) scan showed irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image (Figure 3 ). An enhanced computed tomography (CT) scan revealed diffuse, irregular enlargement of both adrenal glands, with no finding in the testes (Figure 4 A,B). Bilateral testicular atrophy and bilateral enlargement of the adrenal glands without any other metastases did not seem to be typical for malignant testicular tumors. At this point, adrenal gland disease was suspected and an endocrinologist was consulted for further examination. In the endocrinological examination, both the serum ACTH and 17‐OHP levels were extremely high (69.3 pg/mL and 112 ng/mL, respectively). Genetic diagnosis by polymerase chain reaction (PCR)‐direct sequencing confirmed the 21‐hydroxylase deficiency due to CYP21A2 gene mutation (I‐172N mutation) and a low‐dose, oral glucocorticoid of 0.5 mg/d was started under the diagnosis of CAH. After 1 month of glucocorticoid therapy of 0.5 mg/d, the semen analysis revealed a significant change (concentration: 34 × 10 6 /mL; motility: 59%), along with normalization of the testicular size (right: 14 mL; left: 16 mL). The size reduction of the TART was identified by ultrasound (Figure 2 B). The hormonal status had not changed significantly from the pretreatment status (serum FSH: 2.8 mIU/mL; LH: 1.6 mIU/mL; testosterone: 3.2 ng/mL; estradiol: 18 pg/mL). After 2 years of glucocorticoid administration, the clinical pregnancy of his wife was established by using in vitro fertilization (IVF), resulting in the delivery of a female offspring (3650 g) who was confirmed as negative for CAH by serum 17‐OHP and 21‐deoxycortisol measurement.\"}", "questions": ["What abnormalities were identified on scrotal ultrasound for each case, including lesion presence, echogenicity, and vascular characteristics?", "What changes in testicular size were observed after glucocorticoid therapy, and were any palpable indurations or epididymal abnormalities noted?", "What were the results of serum tumor markers (hCG, AFP, LDH) for testicular cancer in each case?", "Describe the MRI characteristics of the testicular lesions (signal intensity, margins, relationship to surrounding tissue) reported in the document.", "What did the enhanced CT scan reveal regarding testicular involvement and the condition of the adrenal glands?", "Summarize the changes in semen analysis parameters (volume, concentration, motility) over the course of treatment for each patient.", "How did the size of adrenal hyperplasia and testicular adrenal rest tumors (TART) change after glucocorticoid therapy?", "What was the primary reproductive concern or diagnosis that prompted medical evaluation for each patient?"], "ground_truth_arguments": ["Bilateral testicular tumors were identified in a scrotal ultrasound echo scan", "both testes had become slightly atrophied ( right : 14 mL; left : 12 mL ) ( performed with a Prader orchidmeter ) and no induration was palpated", "serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 ( Figure 6 A ). The semen analysis showed azoospermia", "Sperm emerged ( concentration : 3.4 × 10 6 /mL; motility : 26 % )", "size reduction in the adrenal hyperplasia and TART", "infertility", "Both testes had become atrophied ( 9 mL ) ( performed with a Prader orchidmeter ) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes ( Figure 2 A ). The semen analysis revealed oligoasthenozoospermia ( volume : 2.6 mL; concentration : 7 × 10 6 /mL; motility : 14 % )", "irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image", "no finding in the testes", "Bilateral testicular atrophy", "semen analysis revealed a significant change ( concentration : 34 × 10 6 /mL; motility : 59 % ), along with normalization of the testicular size ( right : 14 mL; left : 16 mL ). The size reduction of the TART was identified by ultrasound"]}
{"id": "CaseReportBench:train-102", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine. She was born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively. As a 3-week-old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed. At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day. Physical examination revealed multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back. The spleen was of normal size and physical and intellectual development was normal. Again, moderate hemolytic anemia was also found (red blood cells: 3.68 × 10 6, hemoglobin: 10.6 g/dl, hematocrit: 33.0%, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G/DL, platelets 124 × 10 3 ml, white blood cells: 3.6 × 10 3, reticulocytes: 58 (5-15)), but did not require a blood transfusion. Further laboratory investigations were as follows: urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal. Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable. Now, aged 14 years, the severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands. Using all available measures to protect herself from the sun (hat, eyeglasses, cosmetic camouflage, and long sleeves) has not succeeded in protecting her from the mutilating effects of sun. This has caused scarring of her skin at sun-exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp. In addition, she has restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust. Moderate hypertrichosis on the back of the neck was also noted and her teeth have progressively stained brownish-red. The results of the biochemical investigations are summarized in Table 1 . Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High-pressure liquid chromatography of the urine demonstrated 85% of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617. These results confirmed a diagnosis of CEP. Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T>C (p.Cys73Arg) in exon 4 and c.683c>T (p.Thr228Met) in exon 10. These missense mutations have previously been described, where the patient had a moderate to severe phenotype.'}", "questions": ["What hematology laboratory abnormalities were observed in the patient?", "Which serum chemistry results were reported as normal?", "What imaging examinations were described as normal?", "What were the overall findings of the porphyrin investigations?", "What genetic findings were reported for the UROS gene?"], "ground_truth_arguments": ["moderate hemolytic anemia was also found ( red blood cells : 3.68 × 10 6, hemoglobin : 10.6 g / dl, hematocrit : 33.0 %, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G / DL, platelets 124 × 10 3 ml, white blood cells : 3.6 × 10 3, reticulocytes : 58 ( 5 - 15 ) ),", "urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal.", "Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable.", "Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High - pressure liquid chromatography of the urine demonstrated 85 % of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617", "Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T > C ( p. Cys73Arg ) in exon 4 and c.683c > T ( p. Thr228Met ) in exon 10"]}
{"id": "CaseReportBench:train-306", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Report': 'A 63-year-old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A-C ) was referred to our hospital due to an abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm ( Fig. 1D ). He had a history of hypertension for 5 years and a smoking habit (10 cigarettes/day). Coronary angiography revealed mild to moderate coronary atherosclerotic lesions ( Fig. 1E and F ). He was initially suspected of having FH based on his physical findings as well as the presence of AAA with a modestly elevated LDL cholesterol level (166 mg/dL). He was born to consanguineous parents (second cousins). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis. Recessive inherited disease was speculated at this point, so we investigated his genetic background using whole-exome sequencing, assuming a recessive form of inheritance. The mean depth was 99.9× per base across the whole exome. The percentage of on-target reads was 84.6%. Also, the coverage rate of target coding lesions (10×) was 99.0%. Bioinformatics analyses and segregation pattern matching followed by exome sequencing were performed for the patient to identify causative variants. The number of aligned variants in the patient that passed the standard quality control was 142,508. Of those, 15,335 were missense, nonsense, splice site, and frameshift variants. After removing “common” variants ( 10 ), 3,042 variants were detected. Subsequently, filtering against the segregation pattern assuming the recessive form of inheritance with the use of an in silico annotation prediction tool (scaled C-score >20) reduced the candidate variants to homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene (c.410G>A or p.Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ). Accordingly, an increased serum level of cholestanol was found (5.2 μg/mL, reference range 1.62-3.08). The patient did not show any neuropathy, although T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging showed periventricular white matter. Other classical phenotypes of CTX, such as juvenile cataract, chronic diarrhea, and intellectual disability, were not found. Endovascular repair (EVAR) was successfully performed for the treatment of his saccular type AAA. Atorvastatin 10 mg was used to reduce his LDL cholesterol, although chenodeoxycholic acid was not used due to the lack of neuropathy.'}", "questions": ["What are the patient’s age, sex, and the key physical findings (e.g., tendon changes, skin lesions) that prompted referral to the hospital?", "What cardiovascular and lifestyle risk factors (e.g., hypertension duration, smoking habits) are reported in the patient’s medical history?", "What details are provided about the patient’s family background, including parental consanguinity and any family history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis?"], "ground_truth_arguments": ["A 63 - year - old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A - C ) was referred to our hospital due to an abdominal pulsatile mass", "He had a history of hypertension for 5 years and a smoking habit ( 10 cigarettes / day", "He was born to consanguineous parents ( second cousins ). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis"]}
{"id": "CaseReportBench:train-364", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'CASE REPORT': 'A 20-year-old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall-out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva (xerostomia), poor formation of tear (xerophthalmia), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood. The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable. There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar-plantar hyperkeratosis without any other complaints she presented, particularly dental problems. On examination, there were symmetrical, well-demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo/hyper-pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes. On intraoral examination, it was found that patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries. Detailed physical and systemic examinations were unremarkable, except for mild to moderate pallor. Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia. Serological tests like anti-nuclear antibody, anti-cytoplasmic neutrophilic antibody, HIV-I and II, and VDRL were negative. Chest X-ray posterior-anterior view was within normal limit. Orthopantomonograph (OPG) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “floating in air” appearance. At this point, we made a clinical provisional diagnosis of Papillon-Lefevre syndrome, with a possible differential diagnosis of chronic arsenicosis. All the clinical features were in favor of Papillon-Lefevre syndrome, except for those that were similar palmo-plantar hyperkeratotic lesions of her parents and of few neighbors. Histopathology of skin lesions was not done as her parents declined a biopsy. To rule out chronic arsenicosis, we decided to send her hair and nail for estimation of arsenic level by neutron activation analysis at our own costs as she was from a poor family. Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis. She and her parents and affected neighbors were advised to change the source of drinking water. She was initiated with a standard dose of penicillamine as a chelating agent and was referred to a dermatologist for treatment of palmo-planter hyperkeratosis.'}", "questions": ["What is the earliest age at which the patient reported any symptoms related to the condition?"], "ground_truth_arguments": ["since the age of 3–4 years"]}
{"id": "CaseReportBench:train-383", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Patient': 'The patient was the second child of nonconsanguineous parents who was born after an uneventful pregnancy of 42 weeks. At birth, early findings comprised congenital hypotonia, low facial expression, and inverted feet. He was diagnosed with swallowing problems and gastroesophageal reflux. Dysmorphic features included brachyturricephaly, low-set ears, hypermetropia, facies myopathica, and hyperlaxity with arachnodactyly. Due to positive family history of minicore myopathy (his sister died with this condition at age 5 due to aspiration), an early muscle biopsy was performed. The initial histological findings suggested a possible multi/minicore disease. The patient developed chronic lactic acidemia (lactate 2.3–4 mmol/l, C: <2.1 mmol/l), 3-methylglutaconic aciduria (80 μmol/l, C: <18 μmol/mmol creatinine), and recurrent hypoglycemic episodes. Serum alanine levels (610 μmol/l, C: <450 μmol/l) and creatine kinase (CK) levels (500–800 U/l, C: 180 U/l) were moderately increased. No motor development was observed with regular physiotherapy; for further clarification of the diagnosis, a second muscle biopsy was performed at the age of 6 years. The biopsy results showed the characteristic picture of central core disease: electron microscopy detected abnormal, large mitochondria with crystalline inclusions and biochemical evidence of severe mitochondrial dysfunction (Table 1 ). Genetic studies including mitochondrial DNA sequencing, sequencing of the nuclear-coded structural complexes I and III genes, and POLG mutation analysis were all normal. A compound heterozygous RYR1 mutation in complementary DNA (cDNA) was found. The parents were heterozygous carriers (Wortmann et al. 2009 ). At age 9 years, while receiving regular physiotherapy, the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures. Further physical signs were bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees. He had no extraocular muscle anomalies and no exercise-induced myalgia. Table 1 Abnormal biochemical and genetic features Analyses performed Results Biochemistry ATP production nmol/h/mUCS (N 42–81) 4 Complex I mU/UCS (N 70–251) 58 Complex II mU/UCS (N 335–749) 312 Complex III mU/UCS (N 2200–6610) 725 Complex IV mU/UCS (N 810–3120) 483 Complex deficiencies I, II, III, IV Genetics Paternal mutation p. His581GlnfsX29 (exon 16) Maternal mutation p.Val14849Ile (exon 101) ATP adenosine triphosphate, UC unconditioned stimulus, N normal'}", "questions": ["What types of hypoglycemic episodes were noted in the patient?"], "ground_truth_arguments": ["recurrent hypoglycemic episodes."]}
{"id": "CaseReportBench:train-209", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'CASE REPORT': 'A 37-year-old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous (IV) drug abuser that required a permanent indwelling venous catheter for his repeated attacks; so, he had a port since 9 months ago and received pethidine via that port during the attacks. On admission, a chest computed tomography revealed multiple cavities in both lungs. A large mobile veg on anterior leaflet of tricuspid valve commissure (TVC) with severe TR was also demonstrated in his transthoracic echocardiography. After starting antibiotic therapy and removing the port, the patient underwent TV replacement. In the day of surgery, prior to induction, all standard monitorings were applied; radial artery line and subclavian central venous (CV) line was also indwelled after induction. Premedication was consisted of incremental doses of fentanyl and midazolam. We used propofol and atracurium for induction. Maintenance of anesthesia was done by propofol, atracurium, midazolam and fentanyl. Following sternotomy and heparinization, cardiopulmonary bypass (CPB) was initiated. The patient cooled to 32–34°C. Myocardial protection was provided by hypothermic antegrade blood cardioplegic. The TV was replaced. After 70 min of CPB, separation from CPB was achieved, and heparin was reversed by protamine. Rewarming and weaning from CPB was uneventful. Four units of packed cell were given during CPB; Hct was maintained about 30%. Postoperatively, in Intensive Care Unit (ICU), the patient was extubated in 6 h. We started parenteral carbohydrate as dextrose 50% to prevent AIP attack, and the patient was encouraged to become per oral (PO) as soon as possible. Finally, he was discharged from ICU on day 2 after surgery. AB therapy was continued for several weeks. By providing adequate IV crystalloid fluids, we had prevented any dehydration. The patient was cautiously observed for any symptoms of AIP attack. Throughout his stay in ICU, he had no symptoms such as abdominal pain, dark urine, and neurologic deficit.'}", "questions": ["What respiratory symptoms are reported in the case report?", "How are breathing difficulties described in the case report?", "What pulmonary abnormalities are identified on imaging studies?"], "ground_truth_arguments": ["dyspnea", "cough", "paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea", "multiple cavities in both lungs"]}
{"id": "CaseReportBench:train-98", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}", "questions": ["What was the patient's initial hemoglobin level on admission?", "What findings were reported on the initial CT scan regarding the aortic dissection, arch anatomy, aberrant right subclavian artery, periaortic hematoma, and pulmonary venous connection?", "What abnormalities did the subsequent CT scan reveal after the patient's pain recurred, specifically concerning the aortic dissection, false lumen size, aneurysmal dilatation, and pleural fluid collection?", "What did the postoperative CT scan show about the aortic isthmus stent graft, presence of endoleaks, and the status of the subclavian artery orifices and distal runoff?"], "ground_truth_arguments": ["Her initial hemoglobin level was 11.8 g / dL", "An initial computed tomography ( CT ) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch ( ETA ) and an aberrant right subclavian artery ( ARSA ) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection ( PAPVC ) showed that the vertical vein connected to the left upper lobe drained into the left bra - chiocephalic vein", "Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10 % of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased", "CT scan revealed a well - functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run - off reserved from collateral flow"]}
{"id": "CaseReportBench:train-557", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case Report': 'A 38-year-old female presented to the out-patient department with a 6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week. The patient gave no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits. On cutaneous examination, prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin-colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin-colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face. Fundus examination of both eyes showed dark brownish-red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks. 2D-echo and electrocardiogram were investigated to check for cardiac involvement but were normal. A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid-dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material (mucin). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition. Based on the clinical and histopathological findings, a diagnosis of PXE was made. The patient was started on oral and topical sunscreens, advised rigid eye protection to prevent accidental blunt trauma, and regular follow-up.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.'}", "questions": ["What cardiac assessments were performed to evaluate potential involvement?", "What were the principal histopathological observations from the skin biopsy?"], "ground_truth_arguments": ["2D - echo and electrocardiogram were investigated to check for cardiac involvement but were normal", "A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid - dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material ( mucin ). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition"]}
{"id": "CaseReportBench:train-412", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case presentation': \"This is a 20-year-old female with a 6-month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days. Her vital signs on admission showed uncontrolled hypertension (BP = 148/118 mm Hg) and tachycardia (HR = 120 bpm). She was unable to eat during the last few days. On the second day of her admission, she had two generalized tonic–clonic seizures. She received lorazepam and levetiracetam, and her clinical seizures resolved; however, she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region. The patient was transferred to the ICU for blood pressure control and was started on treatment with acyclovir, antihypertensive medications, and antibiotics. She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid (CSF) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus . The brain MRI showed PRES ( Fig. 1 ). Because the stat EEG showed LPDs + F, a highly epileptogenic pattern, cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording. Therefore, clinical and electrographic seizures completely subsided with treatment. Acyclovir was discontinued, and high dose steroids were started, considering the possibility of immunological and inflammatory etiologies. The patient showed clinical improvement, but her abdominal pain persisted, and the diagnosis of an acute porphyria was suspected. Urine, then serum and fecal porphyrins were requested. The results were as follows: urine PBG level was 177.4 μmol/L (reference: 0 to 0.88 μmol/L), serum porphyrin level was 58 nmol/L (reference: 0 to 15 nmol/L), fecal coproporphyrin was 18 nmol/g (reference: 0 to 45 nmol/g), and fecal protoporphyrin was 10 nmol/g (reference: 0–100 nmol/g). Taken together, the highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels, were suggestive of AIP. The patient's abdominal pain resolved in less than 24 h with carbohydrate (glucose) loading and highly caloric diet. Therefore, intravenous hemin was not necessary at that time. She was discharged home in stable conditions and offered to follow up at a porphyria center of her choice for further confirmatory genetic testing, management, and counseling. The patient was seen in our epilepsy outpatient clinic one month later. She was not taking any medications. She was asymptomatic, and her neurological exam was normal. A follow-up brain MRI showed remarkable improvement.\"}", "questions": ["What are the patient's age, gender, and the approximate length of her recurrent abdominal pain before admission?", "What type of previous abdominal surgery did the patient have, and approximately how long before admission was it performed?", "Did the prior surgery relieve her abdominal pain?", "What were the primary diagnoses and presenting symptoms at admission, and how long had these symptoms been present?"], "ground_truth_arguments": ["This is a 20 - year - old female with a 6 - month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days"]}
{"id": "CaseReportBench:train-175", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}", "questions": ["What types of clinical signs could suggest adrenal insufficiency in a neonate?"], "ground_truth_arguments": ["Hyperpigmentation suggestive of adrenal insufficiency was noted"]}
{"id": "CaseReportBench:train-599", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case presentation': \"We present the case of an unsplenectomized man suffering from heterozygous GD1 with mutations of c.1226A>G (N370S) and RecNci I (L444P, A456P, and V460V) in the GBA1 gene, who developed recurrent pulmonary aspergillosis caused by Aspergillus fumigatus and a mycobacterial infection caused by Mycobacterium avium. Despite long-lasting therapy of both aspergillosis (including antifungal drugs and surgery), and the mycobacterial infection (triple therapy with rifampicin, ethambutol, and clarithromycin), recurrent positivity for M. avium and A. fumigatus was detected. A 65-year-old man, originating from northern Greece but living in Sweden for over 30 years, had been referred to the Hematology Center Karolinska for a consultation concerning suspected Gaucher disease. His past medical history was significant for several co-morbidities ( Table I ). Because of splenomegaly (18 cm) and mild thrombocytopenia, a bone marrow (BM) examination was performed at the age of 51, disclosing the presence of foamy macrophages classified as Gaucher cells (GCs). However, further investigations aimed at the confirmation of GD diagnosis were not performed at that time. At the age of 54 years, he developed malaise and a chronic cough. He was a smoker for 25 years but quit at the age of 50. Radiological examination disclosed mild pulmonary fibrosis and aspergillosis in the right lung. The microbiological examination of secretions from a bronchoalveolar lavage (BAL) showed growth of Aspergillus fumigatus and mycobacteria other than tuberculosis (MOTT). Antifungal therapy with itraconazole (100 mg 2 × 2 p.o.) was administered for 6 weeks, but the MOTT infection was not treated. Of note, several weeks after therapy onset, the patient's clinical course was complicated by pulmonary bleeding (the coagulation work-up was normal apart from moderate thrombocytopenia). The fungal infection did not fully respond to therapy, and 2 years after diagnosis the patient underwent a partial resection of the right lung due to an aspergilloma ( Figure 1 ). After surgery, his general status improved rapidly. At age of 59, the patient developed shortness of breath and cough. Echocardiography showed septal left ventricular hypertrophy, normal systolic function of the left ventricle (EF of 50%–60%), signs of diastolic dysfunction, mild insufficiency of both aortic and pulmonary valves, and a slightly elevated pressure in the pulmonary artery (PA) of 42 mmHg. Repeated microbiological examination of the BAL secretions revealed a growth of Aspergillus fumigatus and Aspergillus nidulans, but was negative for MOTT. HIV serology was negative, excluding acquired immunodeficiency syndrome (AIDS). Voriconazole was administered for aspergillosis periodically for 2 years (at the age 61–62 years). Afterwards, the patient's symptoms regressed, and control spirometry showed only moderately decreased results (VC 3.72 L, 82%; FEV 1 3.04 L, 84%; FEV 1 /SVC 82%; FVC 3.72 L, 82%). Chest X-ray did not show any active pathological lesions. However, computed tomography imaging (CT) revealed pronounced fibrosis of lung parenchyma. At the time of hematologic consultation (at the age of 65), thrombocytopenia and hyperferritinemia were noted. The final diagnosis of GD1 was confirmed by the absence of glucocerebrosidase activity in peripheral blood leukocytes and an increased activity of plasma chitotriosidase. Further direct DNA sequencing of the GBA1 gene revealed heterozygous mutations in the GBA1 gene ( Table I ). The patient's status consisting of splenomegaly, thrombocytopenia, and an increased susceptibility to pulmonary infections, which was probably due to lung involvement in the course of GD, was assessed as an indication for commencing treatment of GD. The patient was started on miglustat, which was considered the first line of GD1 treatment at that time due to the worldwide supply shortage of Cerezyme® during 2009–2010 ( 9 ). He received the commercially available miglustat capsules at a dose of 100 mg three times a day orally. Interestingly, the patient experienced an unusually rapid improvement of the whole blood platelet count (PLT), which normalized already after 2 months of miglustat therapy. Unfortunately, the patient developed malaise, diarrhea, poor appetite, weight loss (10 kg, 16% of his baseline body weight), and mild tremor for which miglustat was deemed accountable. During this time, the patient also developed cough, and a microbiological examination of the BAL secretions revealed growth of Aspergillus fumigatus (sensitive to voriconazole) and Mycobacterium avium . Inflammatory activation was observed at that time as presented in Table I . The patient discontinued miglustat after 4 months of treatment due to the adverse events and the above-mentioned pulmonary infections. Voriconazole was administered, and after 10 days his cough decreased but, after some days, returned, alongside malaise and night sweats. CT of the chest disclosed a new infiltrate in the lower lobe of the right lung, despite antifungal therapy ( Figure 2 ). Treatment with rifampicin, ethambutol, and clarithromycin for Mycobacterium avium was initiated. After 4 months of therapy, the patient was stronger, his cough and night sweats were clearly reduced, and he had regained 10 kg of body weight. After the Cerezyme® supply shortage had ceased, the patient was offered to start ERT. Unfortunately, he strongly refused administration of ERT despite our recommendations. Now, almost 2.5 years after the initiation of the triple therapy, and with intermittent periods of negativity, the patient is recurrently positive for Mycobacterium avium in his sputum, despite 8 months of triple therapy administered during the preceding year. During the periods of deterioration in his general condition, he was also positive for Aspergillus fumigatus in sputum.\"}", "questions": ["What is the confirmed diagnosis of the patient’s lysosomal storage disorder?", "What subtype of the identified lysosomal storage disorder was reported?", "Which genetic disorder was diagnosed in the patient?"], "ground_truth_arguments": ["GD1", "Gaucher disease"]}
{"id": "CaseReportBench:train-385", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case Presentation': \"We present a case of cardiac paraganglioma with left coronary artery involvement. The patient was a 22-year-old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension. Results of transthoracic echocardiography and renal Doppler imaging were normal, and plasma and urine metanephrine levels were within normal limits. Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation. New transthoracic echocardiography showed high velocities in the pulmonary artery and a mass with intermediate echogenicity located at the base of the heart in close relation to the aorta and the pulmonary artery, extending into the left atrioventricular groove ( Figure 1, Videos 1 and 2 ). Free metanephrines in plasma (noradrenaline 4,886.67 pg/mL) and urine (noradrenaline 1,426.9 μg/24 h) were high. Figure 1 Transthoracic echocardiography. Shown is a mass ( white arrow ) with intermediate echogenicity in relation to the great vessels. To obtain better characterization, cardiac magnetic resonance was performed and showed a middle mediastinal mass located in the left atrioventricular groove, extending posteriorly to the left atrial roof and almost surrounding the pulmonary artery anteriorly. The mass was closely associated with the aortic root, but the emergence and path of the left coronary artery and its branches were not adequately visualized ( Figure 2 ). Tissue characterization sequences showed a mass with a heterogeneous appearance on T2-weighted sequences and slightly hyperintense on T1-weighted and T2 with fat saturation sequences ( Figure 2 ). Important mass vascularization was demonstrated with the perfusion sequence, which showed rapid uptake of contrast shortly after its administration. We also found focal late gadolinium enhancement at the periphery of the mass, with no enhancement at its center, a finding that was considered highly suggestive of a paraganglioma ( Figure 3 ). Fluorine-18 fluorodeoxyglucose positron emission tomography was also performed, demonstrating a highly metabolic mass ( Figure 4 ). Figure 2 Cardiac magnetic resonance. (1) Coronal: isointense mass in relation to the left atrial roof. (2) Two-chamber longitudinal: isointense mass in the left atrioventricular groove. (3,4) Axial: mass in relation to the aortic root and the pulmonary artery. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 3 Cardiac magnetic resonance. Delayed enhancement. Focal deposit of gadolinium in the periphery of the mass. Images reproduced with permission from Clínica Shaio-Bogotá-Colombia. Figure 4 Positron emission tomography with 18F-fluorodeoxyglucose (10 mCi). Hypermetabolic mass in the middle mediastinum. Images reproduced with permission from Clínica del Country-Bogotá-Colombia. The case was discussed with the heart team and other departments, such as endocrinology and oncology, concluding that the patient had a clear indication for surgery, with α- and β-blockade, high sodium intake, and adequate hydration before the procedure. However, given that there were doubts regarding the emergence of the left coronary artery and its pathway, coronary angiotomography was performed. The mass was found to surround the left main coronary artery, the proximal segment of the left anterior descending coronary artery, the circumflex coronary artery, and two septal arteries, as well as the great cardiac vein ( Figure 5, Figure 6, Figure 7 ). At that time, and because of these findings, the intervention was considered to be a high-risk procedure. Isotopic radiation with 131 I meta-iodine benzyl guanidine (MIBG) was considered as a palliative intervention, but this approach was rejected because of the risk for hypertensive crises of unpredictable severity. Another approach that was considered was the use of octeotride, but this alternative was not accepted by the multidisciplinary group, because there was a risk for irradiation of adjacent tissue, including the coronary arteries, with an unknown benefit. The risk/benefit assessment of this therapy did not favor the patient either, and surgery was thought to be the only option. Coronary angiography was done looking for a main feeding artery that could be embolized preoperatively to reduce the tumor size and intraoperative blood loss. However, embolization could not be done, because there were many small feeding arteries coming from the left main coronary artery ( Figure 8 ). The patient underwent mass resection, requiring a complete transverse arteriotomy of the ascending aorta, pulmonary trunk, and section of the superior vena cava. The mass was exposed using caudal traction and was found to be closely associated with the posterior wall of the ascending aorta, the pulmonary artery, and the left atrial roof, without infiltration of these structures. Involvement of the left coronary artery trunk was documented, which required ligation and revascularization of the anterior descending coronary artery and the circumflex coronary artery. The mass could be completely resected ( Figure 9 ). Figure 5 Coronary computed tomography. Mass surrounding the left main coronary artery and the proximal segment of the anterior descending and the circumflex coronary arteries. Figure 6 Coronary computed tomography. Mass surrounding the pulmonary artery. Figure 7 Coronary computed tomography. Mass located in the left atrioventricular groove. Figure 8 Coronary arteriography. Mass irrigated by multiple small vessels arising from the anterior descending coronary artery. Figure 9 Surgical specimen. Resected mass. The patient progressed well and was able to be extubated and have her vasopressor support discontinued. Follow-up echocardiography showed that systolic function was moderately affected, with an ejection fraction of 35% and diffuse hypokinesia, which was more pronounced in the anterior descending coronary artery territory. Because of these findings, new coronary angiography was performed, ruling out saphenous bridge compromise ( Figure 10 ). Further follow-up echocardiography showed improvement in systolic function, with an ejection fraction of 55% and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure ( Figure 11, Videos 3 and 4 ). Figure 10 Coronary angiography. Saphenous bridge patent to the anterior descending artery, without lesions. Figure 11 Transthoracic echocardiography. (1) Parasternal view in diastole: pericardial effusion. (2) Parasternal view in systole: akinesia of the basal anteroseptal segment. The pathology report of the surgical specimen described round and oval cells in an organoid pattern with fine chromatin nuclei and degenerative focal atypia ( Figure 12 ). These findings and the immunohistochemical studies were compatible with a paraganglioma. The genetic study showed a succinate dehydrogenase subunit B mutation. The patient progressed satisfactorily and was discharged. One month later, it was found that one of her father's cousins had a para-aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain. Figure 12 Round and oval cells, arranged in an organoid pattern, with degenerative focal atypia.\"}", "questions": ["What are the patient's demographic details and the general categories of symptoms she reports, as well as her blood pressure findings?", "Which family members have a history of pheochromocytoma or related tumors, and where in the body were these tumors located?"], "ground_truth_arguments": ["The patient was a 22 - year - old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure", "one of her father 's cousins had a para - aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain"]}
{"id": "CaseReportBench:train-332", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case Report': 'Our case was a 1-year 5-month-old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath-holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium. The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby’s parents were consanguineous cousins. The father’s thalassemia status could not be elicited. On examination, the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm and the baby was conscious and alert. There was no jaundice or dehydration or abnormal odor. Arterial oxygen saturation (SpO 2 ) was 94%. The capillary refill time was between 3 s and 4 s. The heart rate was 146/min. The respiratory rate was 26/min. Non-invasive blood pressure was 73/44 (54) mm Hg. Respiratory system examination revealed normal chest movements with equal air entry on both sides. Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt. Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs. Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal. The eyes, musculoskeletal system, skin, and cardiovascular systems were normal. The baby was admitted for observation and investigations, and the initial differential diagnosis included alkaptonuria, myoglobinuria, hemoglobinuria, porphyria, and hemochromatosis. He had an under-current viral illness, which was managed symptomatically. The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g/dl (normal 10.5-14 g/dl), packed cell volume, mean corpuscular volume (MCV) and mean corpuscular hemoglobin were low at 31.9% (normal 32-42%), 68 fl (normal 72-88 fl), and 21.8 pg (normal 24-30 pg), respectively. MCV concentration was 32% (normal 31.5-34.5%) and red cell distribution width 17.1% (normal 11-16%). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high-pressure liquid chromatography (HPLC) revealed Hb A0 to be 80.4% and Hb A2 to be 6.1% (normal 2.40-3.60). The HPLC picture on correlation with the complete hemogram suggested β-thalassemia trait. DNA studies confirmed the beta globin gene defect of β-thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ-amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine. No abnormalities were detected on the electroencephalogram, leading us to believe that the breath holding spells were due to anemia. Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict’s reagent, strong alkali (filter paper impregnated with 10% sodium hydroxide turned black within 5 min when dipped into the urine) and ferric chloride (addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color). The urine of an alkaptonuric individual usually appears normal when passed. However, it starts to darken upon standing, and this is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Benedict’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test (with multistix) was negative excluding the role of glucose as reducing substance. For the qualitative assay of HA, to 0.5 ml of sample, a few drops of 10% ammonia was added followed by the addition of 3% silver nitrate solution. A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg/dl (normally HA is not present in urine). Parents’ urine was negative for HA. Due to the financial constraints, confirmatory diagnosis by DNA mutation analysis could not be carried out. The child was treated symptomatically, and he was given vitamin C (50 mg once a day for 3 months), low phenylalanine and tyrosine diet, and advised to monitor counts, get liver and renal function tests carried out every 2 weeks. On the request of his parents, the child was discharged after 3 days and advised to follow-up in the outpatient department (OPD). After 3 months post-therapy, his HA levels had not reduced. Currently, the baby is under follow-up every 6 months in the OPD.'}", "questions": ["What specific dietary restrictions were recommended as part of the child's treatment?"], "ground_truth_arguments": ["low phenylalanine and tyrosine diet ,"]}
{"id": "CaseReportBench:train-593", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'CASE REPORT': \"A two-month-old female infant was transferred to Seoul National University Children's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg (<3rd percentile). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion. The initial laboratory findings after birth showed the following increased values on the liver function test: aspartate aminotransferase (AST), 176 U/L; alanine aminotransferase (ALT), 106 U/L; total bilirubin, 1.76 mg/dL; and direct bilirubin, 1.2 mg/dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non-diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract. The patient was fed with preterm formula milk without feeding intolerance. No definitive sepsis event occurred during her hospitalization. When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg/dL and a direct bilirubin level of 9.61 mg/dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum-ascites-albumin gradient level was elevated, and portal hypertension was suspected. By the age of 70 days, the infant was transferred to our hospital for further evaluation of persistent ascites suggesting portal hypertension and hyperbilirubinemia. On the day of admission to our unit, the infant's height was 42 cm (<3rd percentile), her weight was 2.9 kg (<3rd percentile), and her head circumference was 33.5 cm (<3rd percentile). A physical examination indicated whole-body jaundice, a markedly distended abdomen with ascites and an umbilical hernia. The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g/dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg/dL, a direct bilirubin level of 6.4 mg/dL, an AST level of 225 U/L and an ALT level of 114 U/L. The albumin level was 2.4 g/dL, and the ammonia level was increased to 149 µg/dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng/mL (normal values are 14.0-647.2 ng/mL), and the transferrin saturation was 97.2%. The serum alpha-fetoprotein level was in the high normal range (19,737.27 ng/mL; normal values are 40-19,953 ng/mL). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging (MRI) verified a diffuse heterogeneous low signal intensity in the liver on T2-weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra-hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non-diagnostic findings. The infant received supportive medical treatment, including fat-soluble vitamins, ursodeoxycholic acid, fresh frozen plasma, lactulose, diuretics, and sodium benzoate. Her general condition and coagulopathy were aggravated, and her vital signs were unstable. She was transferred to the intensive care unit on day 18 of hospitalization for further management. Her mother began the donor evaluation process. Active gastrointestinal bleeding was observed on day 21 of the infant's hospitalization, and an emergency living donor liver transplantation was performed. The infant was 3 months old, and her weight was 3 kg on the day of transplantation. The graft was tailored by reducing its left lateral section. The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining. The infant fully recovered from hepatic failure after liver transplantation. The infant was discharged one month after the operation. She exhibited normal renal function after transplantation. She received medical treatment for hyperkalemia, which occurred after the administration of tacrolimus. Following her discharge, the patient's neurological development was delayed, and she entered rehabilitation with outpatient clinic follow-up in the hospital's neurology department. Assessments by brain MRI and chromosomal study produced normal findings.\"}", "questions": ["What is the earliest age reported in the document at which the disease manifested or was first noted?"], "ground_truth_arguments": ["birth"]}
{"id": "CaseReportBench:train-496", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Patient’s report': 'The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age. On physical examination she had remarkable pigmentation and normal female external genitalia with no ambiguity. Her body weight had decreased (3,045 g). The laboratory and endocrinological data are summarized in the Table 1 Table 1. Biochemical findings of the patient with CLAH . The electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone (ACTH) level (3,341 pg/ml). The serum 17-hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged (right 1.4 × 1.9 cm, left 1.6 × 1.2 cm) ( Fig. 1A Fig. 1. A: Ultrasonography of adrenal glands. B: Sequence analysis of the patient 1. (B-1) The patient had a one base insertion (246insG) as a heterozygous state. Note overlapping signals after the insertion site. (B-2) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient’s karyotype was 46, XX. She was diagnosed as having adrenal insufficiency caused by CLAH. She was treated successfully with hydrocortisone and fludrocortisones and has grown well.', 'Genetic analyses': 'Informed consent for DNA analysis was obtained from the patient’s parents. The ethical committee of our university permitted this study. To analyze the StAR gene, genomic DNA was obtained from white blood cells by standard procedures. The exons and exon-intron boundaries of the StAR gene were amplified by polymerase chain reaction (PCR) using oligonucleotide primers as described in a previous report ( 3 ). These PCR products were purified and directly sequenced using an automated DNA sequencer (Applied Biosystems, Inc., Foster City CA).'}", "questions": ["What electrolyte findings and endocrine hormone levels (ACTH and 17‑hydroxyprogesterone) were reported for the patient?", "What were the dimensions of the right and left adrenal glands on ultrasonography?", "What StAR gene mutations were detected in the patient?", "What is the patient’s chromosomal karyotype?"], "ground_truth_arguments": ["electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone ( ACTH ) level ( 3,341 pg / ml ). The serum 17 - hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged ( right 1.4 × 1.9 cm, left 1.6 × 1.2 cm )", "The patient had a one base insertion ( 246insG ) as a heterozygous state. Note overlapping signals after the insertion site. ( B-2 ) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient ’s karyotype was 46, XX"]}
{"id": "CaseReportBench:train-610", "dataset": "CaseReportBench", "role": "Dermatology", "document": "{'Case Report': 'A 32-year-old female (gravida 4 para 3) presented to her obstetrician with her next pregnancy following the birth of a previous female child with classical congenital adrenal hyperplasia (CAH). The estimated fetal age was 15 weeks and 4 days at the time of presentation based on initial sonographic assessments. At 19.42 gestational weeks (GWs), ultrasound revealed genitalia that were female-appearing but ambiguous or atypical. A karyotype indicated the fetus was 46,XX with no chromosomal abnormalities. CYP21A2 gene testing of DNA from amniotic fluid showed compound heterozygosity for an R356W mutation on one allele and a 30-kb deletion on the other allele, confirming a prenatal diagnosis of CAH due to 21-hydroxylase deficiency. Parental genetic testing confirmed the fetal genotype. The mother subsequently underwent multiple consultative and care appointments on a bi-weekly/monthly basis with endocrinology, genetic counseling, psychology, urology, and perinatology until delivery at the Fetal Maternal Center, and followed at our CAH Comprehensive Care Center. 1 This next pregnancy led to the surfacing of psychological issues for the proband sibling with regards to her external genitalia, and the related challenges the family experienced during her first year of life, prior to the establishment of our center. It was imperative to immediately address and resolve these issues for both the proband sibling and the family, prior to the arrival of the next affected female child, so that the experience for all family members would be much improved via therapy, education, and a supported effort by the care provider team for CAH. At 29.14 GW, high-resolution prenatal ultrasound (General Electric, 5-9 MHz transducer) was performed and three serial 2D measurements of the biparietal diameter (71.1 mm; 20th percentile) of the fetus and two serial 2D measurements of the head circumference (258.1 mm; 3rd percentile) were averaged and compared with standard references using the Hadlock growth curves. 2 At 30.57 GW, fetal magnetic resonance imaging (MRI; Philips 1.5T) was performed to better evaluate clinically for other abnormalities as MRI can provide information regarding certain conditions like white matter abnormalities and temporal lobe atrophy that cannot be obtained by ultrasound alone. 3 2-D and 3-D MRI measurements of fetal brain structures were computed ( Figure 1 ) and shown in Table 1 . 2-D measurements of brain biparietal diameter, occipitofrontal diameter, skull biparietal diameter, and occipitofrontal diameter, and calculated head circumference were recorded. 4 Significant deficits were noted for skull biparietal diameter and occipitofrontal diameter versus age-matched controls ( Figure 2 ). 5, 6 Absolute biparietal diameter measurements were similar for ultrasound and MRI. 3-D measurements were obtained of the extra-axial cerebrospinal fluid (CSF) volume, supratentorial volume, cerebellar volume, cortical plate volume, and total lateral ventricles volume ( Figure 3 ). 4 Total intracranial volume and deep gray matter volume, but not developing white matter, showed deficits versus controls ( Table 1 ). 5 - 7 A postnatal follow-up MRI of the patient on day 10 of life showed a total brain volume (300.82 cm 3 ) that was below the 5th percentile for age-matched, healthy infants. 8 The neonate was born at 39.14 GW, via uncomplicated vaginal delivery, and seen in the CAH clinic 3 days after birth. On physical examination, she was Prader stage 3, with clitoral width 1 cm, stretched clitoral length 1 cm, and noticeable hyperpigmentation and rugation of the labioscrotal folds. Her examination was otherwise unremarkable. She was a well-appearing neonate with no concerns for adrenal crisis. Hormone analytes were measured at the visit, prior to initiation of treatment, and included: 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone (LC-MS/MS for all; Quest Nichols Diagnostic Laboratory, San Juan Capistrano, CA). The neonate had an elevated serum 17-OHP of 11,500 ng/dL (normal range for term newborns within 12 h of birth: ≤460 ng/dL), androstenedione 4917 ng/dL (normal range not established for newborns; normal range for infants: 6–78 ng/dL), and testosterone 279 ng/dL (normal range of females 1–10 days old: ≤24 ng/dL).'}", "questions": ["What skin changes were noted on the newborn's genital area during the physical examination?"], "ground_truth_arguments": ["hyperpigmentation and rugation of the labioscrotal folds."]}
{"id": "CaseReportBench:train-238", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': 'Phenotypic female twins (A, B) were born at 36+2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g (<10 percentile) in A and 2,040 g (10 to 25 percentile) in B, height was 43 cm (10 to 25 percentile) in A and 44 cm (10 to 25 percentile) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit (NICU). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17-OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17-OHP, elevated ACTH (A, 4,379.2 pg/mL at 23 days of life; B, 11,616.1 pg/mL at 29 days of life), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng/mL/hr). However, the level of plasma cortisol before treatment were normal (8.71 µg/dL initially, 7.11 µg/dL in 2nd sample) in patient A, but low (1.5 µg/dL) in patient B. The results of endocrinologic investigation are shown in Table 1 . The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography (CT) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level (132 to 139 mmol/L) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia (129 to 133 mmo/L) and further evaluation for skin hyperpigmentation. She was treated with oral supplementation of sodium (0.8 to 0.9 mmol/kg) at 11 to 35 days of age, and she discharged from the hospital with normal sodium level after tapering off sodium supplementation at 37 days of age. Patient A was admitted at 38 days of age with adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration. Clinical findings of patient A were suggestive of CLAH and prompted us to order a gene analysis in both twins. Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C>T (p.R182C) in exon 5 and c.722C>T (p.Q258X) in exon 7 ( Fig. 1 ). Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms, except hyponatremia, but she was also diagnosed with CLAH with the same StAR gene mutation with patient A. The results of gene analysis of parents showed heterozygous for the mutations in the StAR gene; the heterozygous gene mutations; c.772C>T in the mother, and c.544C>T in the father, were documented. They showed suboptimal levels of hormone despite of administration of 20 mg/m 2 /24-hr of hydrocortisone, dose of hydrocortisone was increased up to 30 mg/m 2 /24-hr. Both patients have been under steroid supplementation (fludrocortisones 0.2 mg daily in 2 divided doses, and hydrocortisone 12 mg daily in 3 divided doses) at 14 months of age. They showed normal development except retarded physical growth, and hormones and electrolyte levels on follow up are shown as Table 1 . Body weight was 8.8 kg (3 to 10 percentile) in patient A, 9.4 kg (10 to 25 percentile) in patient B, body length was 73.7 cm (3 to 10 percentile) in patient A, 75.4 cm (10 to 25 percentile) in patient B at 14 months of age. They had been regularly followed.'}", "questions": ["What is the age of the patients at the time of the reported follow‑up assessment?"], "ground_truth_arguments": ["14 months of age ."]}
{"id": "CaseReportBench:train-146", "dataset": "CaseReportBench", "role": "Endocrinology", "document": "{'Case 5': 'A 62-year-old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5-year history of an asymptomatic eruption on the neck. Physical examination revealed numerous soft, oval-to-round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area. Echocardiography was unremarkable. The ophthalmologic examination was normal. Moreover, no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption.', 'Histopathology of cases (1–3)': 'A skin punch biopsy was performed, and the hematoxylin and eosin (H and E) sections revealed a normal-appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.', 'Histopathology of case 4 and 5': 'H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident.', 'Case 3': \"A 68-year-old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years. Physical examination revealed numerous tan to yellowish soft papules over the lateral side of the patient's neck, measuring 2–3 mm. The patient had no systemic symptoms and was otherwise healthy.\", 'Case 4': \"A 61-year-old female patient presented to the clinic with a 2-year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis. On physical examination, there were multiple symmetrically distributed, skin-colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient's neck, upper chest, and the antecubital fossa of both forearms. There was no history of sun exposure or family history of similar cutaneous manifestation.\", 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Case 2': \"A 77-year-old female presented with a 4-year history of gradual appearance of small skin-colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension. However, other systemic examinations were unremarkable, especially for eye, cardiac, or gastrointestinal systems.\", 'Case 1': 'A 71-year-old female presented with a 1–2-year history of asymptomatic skin-colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints. Given the clinical resemblance to PXE, an ophthalmology consult was performed to rule out the presence of angioid streaks. The eye examination was normal.'}", "questions": ["What endocrine or metabolic disorders are mentioned for any of the patients?"], "ground_truth_arguments": ["diabetes mellitus Type 2,"]}
{"id": "CaseReportBench:train-259", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case': \"A 27-year-old female was admitted to the hospital because of left hemiplegia and aphasia. She was 162 centimeters tall and 30 kilograms in weight. She was born after a normal pregnancy and delivery. There was no family history of neurological diseases. Motor and intellectual development was normally attained during infancy. She was hospitalized for general muscle weakness and gait disturbance when she was 6 years old. A neurologic exam showed decreased muscle tone and strength, and atrophic muscle mass. She had consistent muscle weakness, so a muscle biopsy was performed from the calf muscle when she was 8 years old. The biopsy showed mitochondrial myopathy of the pleoconial type. Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems. Follow-up procedures were performed in an outpatient clinic once or twice a year. When she was 24 years old she had sudden syncope. An magnetic resonance imaging (MRI) revealed acute infarction of the left basal ganglia and the left frontal lobe. Two years later, when the patient was 26, she had another stroke and presented with general weakness, aphagia, and dysarthria. An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia. These clinical and radiological findings suggested brain involvement of MELAS syndrome. Thus, further evaluation was done for MELAS syndrome including blood lactate and genetic analysis. The plasma lactate level was 21.8 mg/dL (normal range 4.5-19.8 mg/dL). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng/dL (normal range 0.89-1.76 ng/dL) and TSH was 0.04 µIU/mL. Levels of complement component 3 and 4 were 13 mg/dL (normal range 75-145 mg/dL) and 18 mg/dL (normal range 12-72 mg/dL) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti-double stranded DNA was 1.6 (normal range 0-6). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation: m.3303C>T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome. She was treated with supportive care and rehabilitation for a month and was then discharged. Warfarin was used during the hospital stay, but was stopped when she was discharged, because MELAS syndrome causes nonvascular infarct and there is no report about the related risk of thromboembolism. One year later, she presented with another stroke with associated left sided weakness, and was subsequently admitted to the hospital. Her vital signs were stable and there were no specific findings in chest X-rays or electrocardiography. Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25%. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 ). The patient's mental status and general condition improved after she was treated with mannitol and anticoagulation therapy. Rehabilitation and supportive care, including warfarin, were followed and maintained. The patient was discharged after a month.\"}", "questions": ["What does the patient's family history reveal about neurological diseases?", "How were the patient's motor and intellectual development described during infancy?", "At what age was the patient first hospitalized, and what general symptoms prompted the admission?", "What acute event did the patient experience when she was 24 years old?", "What stroke-related event occurred when the patient was 26 years old?"], "ground_truth_arguments": ["no family history of neurological diseases", "Motor and intellectual development was normally attained during infancy.", "hospitalized for general muscle weakness and gait disturbance when she was 6 years old.", "24 years old she had sudden syncope", "when the patient was 26, she had another stroke"]}
{"id": "CaseReportBench:train-405", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': 'A 13-year-old boy born out of a consanguineous marriage presented to the outpatient department with hyperpigmentation and hypertrichosis of lower extremities and trunk for last 4 years. The patient also had hearing loss for more than 5 years which was progressive and was using hearing aid for the same. There was no family history of similar skin changes. On mucocutaneous examination well defined, bilaterally symmetrical hyperpigmented, indurated plaques with marked hypertrichosis were present over medial aspect of thighs and legs. Knees and feet were spared. Similar lesions were present over sacral area and lower back bilaterally. General physical examinations showed mild hepatomegaly and pallor. He had short stature for his age (131 vs. 154 cm). Hallux valgus was also present. Routine laboratory investigations revealed haemoglobin to be 6.7 g/dl. Liver function tests, thyroid profile, serum cortisol (15.25 μg/dL), and blood sugar were normal. Chest X-ray was normal. Antinuclear antibody was negative. Growth hormone level was reduced to 0.77 ng/ml (normal range 1–14.4 ng/ml). Serum Vitamin D3 level (51.88 vs. 81–250 nmol/L) was found to be low. No “M” spike was seen in serum protein electrophoresis. Ultrasonography (USG) abdomen revealed mild hepatomegaly. USG of scrotum was normal. Contrast enhanced computed tomography head, and orbit revealed bilateral mild axial proptosis. Skin biopsy was taken from the hyperpigmented plaque on the thigh and revealed mild irregular acanthosis, and increased melanin deposition in basal keratinocytes. Significant thickening of collagen bundles in upper and mid-dermis was seen along with perivascular infiltrate of histiocytes. Immunohistochemistry was positive for CD68 and CD45 in dermal perivascular histiocytic infiltrate and for CD34+ in vessel endothelium. The final diagnosis of H syndrome was made based on the characteristic clinical and histopathological findings.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient had given his consent for his images and other clinical information to be reported in the journal. The patient understood that his name and initial would not be published and due efforts would be given to conceal his identity, but anonymity could not be guaranteed.'}", "questions": ["What finding indicating liver enlargement was reported in the clinical examination or imaging?"], "ground_truth_arguments": ["mild hepatomegaly"]}
{"id": "CaseReportBench:train-65", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case Report': \"An eleven month old female child, born of a primigravida mother of non-consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal. There was no similar illness in the family. Her pulse rate was 102/min, blood pressure was 84/58 mm of Hg. and respiratory rate was 25/min. Her weight was 7.9 kg, length was 70 cm and head circumference was 45 cm. There was some pallor. Blisters were present on scalp, face, upper and lower limbs with atrophic scars on scalp and upper limbs along with alopecia. Copper-red discoloration of the two erupted teeth was noted. There was no hepatosplenomegaly. Neurological examination was normal. On the basis of infancy-onset blistering over sun-exposed areas, atrophic scars, red colored urine and teeth without neurological involvement and evidence of arthritis, we reached the provisional diagnosis of CEP. Complete blood count showed mild anemia; Hb-9.2 mg/dl, total leucocyte count-8,200 and platelet count of 1.4 lac/cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2% of circulating erythrocytes (normal upto 2%). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol/mmol of creatinine (normal < 35 nmol/mmol). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method (normal value < 40 mcg/100 ml). Bright red fluorescence was also noted in the urine, teeth and blood under wood's lamp. So, a final diagnosis of congenital erythropoietic porphyria was made. Demonstration of deficiency of UROS activity and genetic study could not be performed due to lack of laboratory facilities.\"}", "questions": ["What findings were reported regarding the presence or absence of hepatosplenomegaly in the patient?"], "ground_truth_arguments": ["no hepatosplenomegaly"]}
{"id": "CaseReportBench:train-465", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumor was made; biopsy was deferred and hormonal treatment was modified. A 9-year-old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour. The cortisol level was low, and levels of 17 alpha-hydroxyprogesterone, plasma corticotrophin (ACTH), and testosterone were high. Scrotal ultrasound revealed well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses with posterior acoustic shadowing in both testes, in the medial aspects near the mediastinum testis. The right testicular mass measured 1.3×1.1 cm, and the left testicular mass measured 1.5×1.2cm ( Figures 1, 2 ). On colour Doppler, the masses had minimal internal vascularity ( Figure 3 ). The rest of the testes showed normal flow. The epididymis and cord structures were normal. There was no evidence of hydrocoele on both sides. Testicular tumor markers were negative. Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement ( Figure 4 ). In a patient with CAH and bilateral testicular masses that had a typical sonographic appearance, a diagnosis of testicular adrenal rest tumor was made, and biopsy was deferred. Hormonal treatment was intensified, and the testicular masses are followed up. The patient improved clinically, which was associated with a decrease in testosterone and 17 alpha-hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months. Currently, the patient is advised to undergo follow-up ultrasound examinations every 3 months.'}", "questions": ["At what age was the patient diagnosed with congenital adrenal hyperplasia?"], "ground_truth_arguments": ["age of 1 year"]}
{"id": "CaseReportBench:train-616", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case 2': \"A 13-year-old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks. On examination, there were severe atrophic scars on the face and exposed parts of the extremities, which had resulted in mutilating deformities of the fingers. Hypertrichosis, pigmentation, and milia formation were also present on the face. Though erythrodontia was not spotted with the naked eyes, the teeth revealed a pink-red fluorescence under Wood's lamp. Histopathological examination of an intact bulla revealed the subepidermal location of the blister. A clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity, blistering, and hypertrichosis. The early onset and the mutilation of the fingers were highly suggestive of CEP. The patient was investigated. Routine investigations, including liver and renal function tests, were within normal limits except for mild anemia (Hb 8.0 g/dl, reticulocyte count 7% of circulating erythrocytes). ELISA for HIV was negative. PBG was normal in urine. On screening with a spectrophotometer, urinary total porphyrin was 1187 nmol/mmol of creatinine (normal <35 nmol/mmol). Twenty-four-hour urinary levels of uroporphyrin and coproporphyrin were raised. The erythrocytic porphyrins showed a level of 124.3 μg/100 ml (reference value less than 40 μg/100 ml using the hematofluorometric method). A diagnosis of CEP was made.\", 'Case 1': \"A 3-year-old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks. On examination, the child's face was badly scarred. There was hypertrichosis on the shoulders, arms, and face. The teeth were of coppery-red color. There were a few intact blisters and crusted lesions on the hands and feet. Atrophic scars were also present on the extremities. On the basis of the history of blistering on the exposed areas since early infancy, healing with atrophic scarring, erythrodontia, and red-colored urine, we made a clinical diagnosis of CEP. Routine investigations were within normal limits except for mild anemia. The urine did not show increased level of porphobilinogen (PBG). Further investigations were not carried out. The child was treated symptomatically.\"}", "questions": ["What diagnosis was reported in the case?"], "ground_truth_arguments": ["A diagnosis of CEP was made ."]}
{"id": "CaseReportBench:train-437", "dataset": "CaseReportBench", "role": "Cardiovascular-System", "document": "{'CASE REPORT': 'A 17-year-old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen. She initially presented to a private nursing home where she was intubated and transferred to our hospital on portable ventilator. On examination she was conscious (E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent. Her heart rate was 120/min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator. Systemic examination was insignificant. She was transferred to intensive care unit with a diagnosis of acute inflammatory demyelinating polyneuropathy. She also had features suggestive of autonomic neuropathy in the form of postural hypotension, tachycardia, and sweating. Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X-ray, electrocardiography, electroencephalography were normal. Cerebrospinal fluid analysis was normal. Urine Watson–Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia (serum sodium 126 mmol/L). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits. Nerve conduction study showed axonal motor neuropathy. She was treated as a case of AIP with high dose of carbohydrate (300–400gm/day), heme arginate (3 mg/kg/day for 4 days) and gabapentin for seizures control. Precautions were taken not to prescribe any porphyrogenic drugs. At 60 th day of her ICU stay ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium (10.8 mg/dl) and phosphorus levels (5 mg/dl) were within normal limits. Tracheal tube aspirate for acid-fast bacilli was negative for 3 days in continuation. Patient required prolonged ventilator support and was finally discharged with the advise to follow up.'}", "questions": ["What autonomic manifestations were documented in the patient?", "What were the results of the initial electrocardiography and electroencephalography performed on admission?", "What cardiac findings were later observed, including any ECG changes, cardiac enzyme results, and echocardiographic abnormalities?"], "ground_truth_arguments": ["postural hypotension, tachycardia, and sweating", "electrocardiography, electroencephalography were normal", "ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction"]}
{"id": "CaseReportBench:train-563", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Description': 'Polyhydramnios in the second and third trimester of pregnancy is defined by (semiquantative) measurements such as a maximum vertical pocket (MVP) >8 cm, or an amniotic fluid index (AFI) >24 cm. Approximately 90% of cases are idiopathic or caused by gestational diabetes (GDM) 1 . However, 10% of cases are associated with fetal structural abnormalities 2 . Most frequent causes are impaired swallowing from any cause (gastrointestinal, facial, musculoskeletal, or brain abnormalities), cardiac failure, hydrops, and renal abnormalities. Metabolic diseases, such as congenital disorders of glycogen storage, are also incidentally reported to present with polyhydramnios in pregnancy 3 . The usual diagnostic work‐up of polyhydramnios is to exclude GDM and maternal infections, and to perform an extensive structural assessment to rule out fetal anomalies. The presence of structural anomalies, involves increased risk of aneuploidy or other chromosomal and syndromic disorders. In isolated polyhydramnios, the risk of perinatal adverse outcome is, however, still increased when compared with uneventful pregnancies 4 . A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios. Aside from a spontaneously closed ventricular septal defect (VSD) in her own infancy, both parents were healthy. A maternal uncle of the mother had died postnatally of an unknown cause. First‐trimester combined test revealed a low risk for trisomies (NT 1.1 mm). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios (uterine size that outpaced gestational age) and premature contractions. She received tocolytics and corticosteroids for fetal lung maturation. Ultrasound showed polyhydramnios (MVP 9.9 cm, AFI 27.5 cm) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles (11 mm). Amniotic fluid drainage (1.8 L) was performed in an attempt to cease the premature contractions. More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna (12 mm) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm (slightly below p3, with head circumference p50, Fig. 1 A). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD. QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 (11q22.1), including exon 1 of the contactine 5 ( CNTN5 ) gene. This variant is not reported as genomic variant in the normal population, neither known to be associated with a genetic disorder or malformation. A relation with the clinical signs appears unlikely. Maternal serum infection testing (TORCHES) was also normal. Two days later (26 + 0), she spontaneously delivered a boy of 835 g (−0.5 SDS), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively. At birth, he was started on CPAP and transported to the neonatal intensive care unit. Physical examination showed a hypotonic infant with a lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus (Fig. 1 B). He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges. The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels. Testes were not palpable in the scrotum. Postnatal cardiac ultrasound confirmed the presence of a small VSD. Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy. A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome. He developed hypotension and was treated with fluid boluses and inotropic support and antibiotics. Despite stabilization of blood pressure and systemic circulation, he developed a progressive lactate acidosis with extremely high plasma lactate: 19.1 mmol/L and high pyruvate: 269 μ mol/L. The L/P (lactate/pyruvate) ratio was 71, which is strongly increased (normal <20). Organic acid analysis in urine showed a strong increase of lactate (56540 μ mol/mmol creatinine) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal. In the absence of secondary causes, these findings are consistent with primary lactic acidosis, caused by a disorder of the pyruvate metabolism or a mitochondrial respiratory chain defect. Due to the severity of the cumulative problems, the neonate died 2 days after birth. Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst (Figure S1C), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst (Figure S1D). DNA analysis of the PDHA1 ‐gene (most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency) showed no pathogenic mutations. Large deletions, point mutations, and small insertions/deletions in mitochondrial DNA (mtDNA) derived from blood were excluded by next‐generation sequencing (NGS) using the Illumina MiSeq platform and a dedicated bioinformatics pipeline (available on request). For whole exome sequencing, exome enrichment was performed by the Agilent SureSelectXT exome enrichment kit version 4, including the UTR regions. Sequencing was performed by an Illumina HiSeq2000 (San Diego, CA) using a 2 × 100 bp paired‐end recipe. Basecalling, and demultiplexing was done using bcl2fastq 1.8.4.,(Illumina, San Diego, CA) reads were aligned onto the human reference genome (hg19) using BWA 0.5.9., duplicates marked using the PICARD software suite 1.77 (GitHub Enterprise, San Francisco, CA), and variants were called using GATK 2.1‐8. Annotations were added using an in‐house build annotation database, according to UCSC RefGene track, dbSNP137, and the dbNSFP (v2.0). Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing: c.292C>T (p.(Arg98*))and c.1303C>T (p.(Arg435*)). Both are nonsense mutations resulting in a premature stop codon at position p.98 and p.435 of the FBXL4 protein, respectively. The location of these mutations on different alleles (compound heterozygosity) was confirmed by testing the parents. Missense and stop mutations in the FBXL4 gene were reported recently to be associated with severe autosomal recessively inherited mitochondrial encephalomyopathy 5, 6, 7, 8 . Our case is the first case demonstrating a premature prenatal onset of symptoms of FBXL4‐ related mitochondrial encephalomyopathy. The polyhydramnios was the primary sign, leading to the detection of brain abnormalities on more detailed fetal ultrasound examination. This early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements. The cases of FBXL4 ‐related encephalopathy reported so far are characterized by increased serum lactate level, psychomotor delay, hypotonia, failure to thrive, swallowing difficulty, and muscle wasting 6 . Onset of symptoms varied from neonatal onset after term birth, to the age of 14 months 5, 6, 8 . Other reported cases were born at term or premature due to medical intervention for intrauterine growth retardation or reduced fetal movements 5, 6 . The FBXL4 gene is situated on nuclear DNA on chromosome 6q16.1. The FBXL4 mitochondrial protein contains an F‐box in its N‐terminal half, followed by 11 leucine‐rich repeats 9, and is expressed in heart, kidney, liver, lung, pancreas, and placenta 10 . Evidence of the pathogenetic effect of FBXL4 mutations was provided by skeletal muscle biopsies and fibroblasts showing defects in mitochondrial respiratory chain enzyme activities, loss of mitochondrial membrane potential, a disturbance of the dynamic mitochondrial network, and mtDNA depletion 5 . The nonsense mutation p.Arg435* in the FBXL4 gene, present in our patient, was earlier reported in homozygous form in a child of consanguineous parents with early onset mitochondrial encephalopathy, severe hypotonia, cardiomyopathy, MRI abnormalities, increased serum lactate, and premature death 5 . The second mutation detected in our patient (p.Arg98* mutation) has not been reported previously. However, like the other mutation reported, this nonsense mutation leads to nonsense‐mediated decay (NMD, RNA degradation) or a truncated protein 5, 6 . As a result, our patient would have been unable to produce a normal FBXL4 gene product. The mother was pregnant again before exome sequencing had started. Within the prenatal timeframe, exome sequencing lead to the diagnosis of the first child, consequently enabling prenatal diagnosis for the second child. Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child. The VSD in our patient is considered to be a separate finding (familial trait), which is not related to the syndrome. Our case demonstrated a prenatal onset of mitochondrial encephalomyopathy presenting with polyhydramnios, causing premature delivery, and cerebellar atrophy. The neonate was hypotonic and in a poor condition with need for mechanical ventilation, inotropic support, and persistent lactate acidosis. Targeted exome sequencing using a mitochondrial gene panel proved its benefit by revealing compound heterozygous mutations in the FBXL4 gene. Prenatal testing was successfully carried out in the current pregnancy. Direct testing for mutations in the FBXL4 gene should be considered in patients with severe encephalomyopathy with high levels of serum lactate.'}", "questions": ["Describe the fetal ultrasound findings related to ventricular dimensions and posterior fossa structures.", "Summarize the neurological examination findings and clinical status of the newborn immediately after birth.", "Detail the postnatal cranial imaging results, including ultrasound and MRI, highlighting hemorrhagic lesions and cerebellar abnormalities.", "What observations indicated reduced fetal movements or hypotonia during the prenatal period?", "What definitive metabolic diagnosis was established for the infant?", "Which specific brain region was reported to be atrophic in this case?", "What supportive therapies were required for the newborn's respiratory and circulatory insufficiency?"], "ground_truth_arguments": ["mild dilatation of both lateral ventricles ( 11 mm ).", "showing an enlarged cisterna magna ( 12 mm ) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm ( slightly below p3, with head circumference p50, Fig. 1 A ).", "hypotonic infant", "Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy.", "Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst ( Figure S1C ), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst ( Figure S1D )", "brain abnormalities on more detailed fetal ultrasound examination", "hypotonia and diminished fetal movements", "mitochondrial encephalomyopathy", "cerebellar atrophy", "hypotonic", "poor condition with need for mechanical ventilation,"]}
{"id": "CaseReportBench:train-251", "dataset": "CaseReportBench", "role": "Respiratory-System", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["Which respiratory symptoms, such as breathlessness or chest pain, were reported by the patient during exertion?", "What were the findings of the chest auscultation examination?", "What did the chest X‑ray demonstrate about the condition of the lung fields?"], "ground_truth_arguments": ["not associated with breathlessness or chest pain", "His chest was clear on auscultation", "clear lung fields"]}
{"id": "CaseReportBench:train-91", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["What are the patient’s age, gender, and relevant past medical history?", "Which medications was the patient taking at the time of presentation?", "How many days of abdominal pain did the patient report before presenting to the hospital?", "How would you describe the severity, location, radiation, and associated symptoms of the abdominal pain?", "What recent activities or physiological states (e.g., exercise intensity, menstrual cycle phase) did the patient report?", "Did the patient seek medical attention at other facilities prior to this admission, and if so, how many times?"], "ground_truth_arguments": ["A 26 - year - old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications ( OCPS ), presented with a 5 - day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities.", "The abdominal pain was severe, generalized, non - radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle"]}
{"id": "CaseReportBench:train-347", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What dosage and route of administration were used for the arginine therapy provided to the patient?", "What dosage and route of administration were used for the citrulline therapy given to the patient after the arginine treatment?"], "ground_truth_arguments": ["high - dose intravenous arginine then oral citrulline at 0.5 mg / kg"]}
{"id": "CaseReportBench:train-269", "dataset": "CaseReportBench", "role": "Eyes-Ears-Nose-Throat", "document": "{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': \"A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.\", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}", "questions": ["What ocular signs and symptoms are described for the patients?", "What ear-related abnormalities are reported in the cases?", "What descriptions of the nose are given in the document?", "What dental findings are mentioned for the patients?", "What findings were observed on Wood’s lamp examination?", "What oral cavity features are described in the cases?"], "ground_truth_arguments": ["having had photophobia and diminished vision in the right eye", "partial absorption of both ears; and brownish - pink - colored teeth", "Ectropion and bilateral keratoconjunctivitis were apparent", "recurrent keratoconjunctivitis and complications", "microstomia ( Fig 3 ), erythrodontia", "Wood 's lamp examination revealed pink - red fluorescence of the urine and teeth", "redness and matting of both eyes", "deformities of her eyelids, making it difficult to close them fully", "reddish - brown tooth discoloration and disfiguration of the nose, ears", "Eye examination revealed severe ectropion, trichiasis, and scleral melting", "reddish - brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting"]}
{"id": "CaseReportBench:train-6", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': 'A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to house soiling and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. The environment consisted of two young adult humans with no children. They lived in a flat of 85 m 2, with two terraces of 5 m 2 each. There were three separated litter boxes at home, all of which were non-covered with low sides. The owners had used clumping, non-clumping, silica-based and soil-based litter during the months between the adoption (when the cat was 4 months old) and the first visit. One of the latrines always had clumping substrate. There were three food and three water troughs, all of them far from the latrines. The impression of the owners was that the cat eliminated where it was at any given moment. It eliminated many more times in front of the owner (90%) than when it was alone (10%). The cat never tried to cover its faeces or urine after depositions. Occasionally, the owners punished the cat verbally and physically, but only when it eliminated in front of them. The substrates used by the cat were ceramic tiles, the sofa and beds. It always adopted an emptying-body posture. Spots were always located on horizontal surfaces. The owners used bleach-based products in order to clean the spots, and just water in the case of the sofa and beds. Regarding the play-related problem, the owners said that the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘tried to bite, catch and scratch the air’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat’s behavioural history was unremarkable. The differential diagnoses of the house-soiling problem included problems with the litter trays, including insufficient number, incorrect type, competition with other cats for the latrines, incorrect location, acquired aversion, or inappropriate substrate; a preference for another location or substrate; a problem with preference acquisition (ie, because of a cognitive impairment, or a sensory impairment or an unavailability of appropriate latrines or substrate during the first few weeks of life); and marking behaviours. Finally, a medical illness can contribute to all of these problems or to be the main cause. 1, 2 We could rule out most of these problems after interviewing the owners. Firstly, it was unlikely that there was a problem with the litter tray because the number, type and location were correct. The locations were correct because the animal eliminated near the litter tray if it was there. Many different substrates had been used. Secondly, it was not a problem of preference because the cat eliminated in different locations and surfaces. The age of the animal, the distribution of the spots and the body posture during elimination ruled out marking behaviours. Alterations in play behaviours described by the owners could have been due to a cognitive impairment, and/or a sensory impairment (ie, blindness). Play behaviours depend on learning capability and sensory systems. 3 Additionally, an enriched environment is necessary to learn and display play behaviours in a proper manner. 4 In that case, the social and instrumental environment was good. Regarding elimination, a problem of substrate preferences acquisition was diagnosed. A cognitive impairment, a medical condition or both could have been the cause of the problem during the elimination habits acquisition. Moreover, cognitive impairment and some medical conditions also could explain the play-related behavioural problems. During the consultation, the physical examination was unremarkable; however, the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. A complete ophthalmological examination was performed by the ophthalmological service in order to rule out ocular diseases. No ophthalmological abnormalities were detected. Additionally, based on the behaviours at home described by the owners (the inability to find some toys, and the behaviour of ‘scratching and biting the air’), some degree of visual impairment was suspected but not confirmed with the neurological examination. The cat did not crash with objects either at home or at the consultation room. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits. The feline immunodeficiency virus/feline leukaemia virus test was negative. A thorax radiograph, abdominal ultrasound, brain magnetic resonance imaging (MRI; 0.2 T) and cerebrospinal fluid analysis showed no abnormalities. Although some small lesions could be missed with low-field MRI, we had to assume the absence of lesions obtained in the work-up. Thus, a degenerative condition such as a lysosomal storage disease, organic aciduria or mitochondrial encephalopathy was suspected. Samples of blood and urine were sent to the University of Pennsylvania School of Veterinary Medicine for metabolic screen tests. Amino acids, organic acids, carbohydrates, nitroprusside, ketone and mucopolysaccharide concentrations were analysed, as was α-mannosidase, β-mannosidase, fucosidase and hexosaminidase A and B activity. All of these were within normal limits. No treatment was prescribed for the neurological problem. The owners were given advice on correcting the soiling problem in the house using reward-based training with a clicker. During the first week, the clicker was conditioned by a food reward, and the entire floor was covered with newspaper. Each time that the cat eliminated, it was rewarded with a clicker and food. Newspaper was removed progressively. Three months later, the cat used a small newspaper-covered area to eliminate. This partial improvement suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability. After 3 months, the cat was referred to the neurology service again, in status epilepticus. Neurological findings, after the postictal phase, included a lack of bilateral menace response and cerebellar ataxic gait. A bilateral carpal valgus that had already been found in the first visit and a visible suture line in the posterior capsule of both crystalline lenses were also detected. The owners reported progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status (probably seizure activity). A symptomatic treatment with diazepam (1 mg/kg intrarectally only if seizures) and phenobarbital (2 mg/kg PO q24h) was started, with a very poor response. After 15 days of treatment, levetiracetam was added (10 mg/kg PO q8h) owing to an increase in seizure activity, with an initially good response. However, seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting <2 mins. After 2 years of treatment and a progressive worsening, the cat was euthanased. A complete necropsy was immediately performed. No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS. In order to rule out prion aetiology, a PrPsc inmunohistochemistry assay was performed, and the results were negative. Thus, congenital spongiform polioencephalomyelopathy (CSP) was diagnosed postmortem. Spongy vacuolation seen by light microscopy in the neural tissue is defined as spongy degeneration, and may take the form of vacuoles within processes of the neuropil, vesiculation of myelin sheaths, or swelling of astrocyte or oligodendrocyte cytoplasm. 5 A congenital problem, retrovirus infection and prion disease have been suggested as possible aetiologies. 6 – 10 Congenital spongiform degeneration of the grey matter has been previously described in a few cases of cats; 6 – 8 however, the cause remains still unknown. Common clinical signs include gait alteration, seizures, blindness, bilateral cataracts, behavioural changes and cranial nerve alterations. These signs appear during very early stages of development (just after birth), with a progressive fatal outcome in a few days or months. Behavioural signs are poorly described in animal science literature. 6 – 8 Although the degeneration usually affects diffusely all the grey matter, the behavioural alterations and the evolution of the clinical signs depend on the affected area of the brain in each case. Nevertheless, the clinical signs do not always correlate with the degree of the histological lesions. A spongy degenerative problem of grey matter has also been described in humans, and occurs in isolated cases and in sibs. 11 – 13 In all of human cases reported, the problem appears early in infancy and the outcome is always fatal. All the affected children show learning disabilities (ie, retarded speech development) during the early periods of infancy. Additionally, they rapidly develop neurological signs, especially seizures. The clinical findings and neuropathological changes are very similar in humans and the present case. There are no studies regarding degeneration of grey matter and its effect on learning ability in animals. However, other neurodegenerative problems (ie, lysosomal storage diseases) and problems that lead to structural abnormalities of the forebrain (ie, hydrocephaly) may be correlated with learning disabilities in animals and humans. 14 – 17 The acquisition of the elimination habits occurs during the first weeks of a kitten’s life. Most kittens naturally seek out sand-like materials for elimination purposes. However, the preference for a substrate needs to be learnt during those first weeks of age. Learning disabilities and/or sensory impairments could modify the acquisition of these habits.'}", "questions": ["What was the age of the cat at the time of presentation to the behavioural service?"], "ground_truth_arguments": ["7 - month - old"]}
{"id": "CaseReportBench:train-620", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'2. Case presentation': 'A 26-year-old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications (OCPS), presented with a 5-day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities. Multiple pelvic examinations and 3 computerized tomography (CT) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen. The abdominal pain was severe, generalized, non-radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle. On prior hospitalizations, her recurrent abdominal was assumed to be secondary to a ruptured ovarian cyst. On presentation, initial laboratory studies showed hypokalemia (potassium 3.4 mmol/L, reference range 3.5–5.1 mmol/L), and an elevated creatinine 1.14 mg/dl (baseline around 0.80 mg/dl). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit, which was managed conservatively ( Fig. 1 ). Patient also reported tingling sensation in her hands and red discoloration of urine. On hospital day 2, serum sodium decreased abruptly from 136 mmol/L to 127 mmol/L (range: 135–145 mmol/L). Serum osmolality was low at 271 mOsm/kg (range: 280–300mOsm/kg), urine sodium was markedly elevated at 168 mmol/L and urinalysis was remarkable for increased urine specific gravity (>1.042). A diagnosis of Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) was made, and water restriction and salt tablet intake were initiated. Early hospital course was complicated by significant hypertension (systolic blood pressure 180 mm Hg), acute visual disturbances followed by seizure and postictal confusion. Magnetic Resonance (MR) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES and Levetiracetam was initiated ( Fig. 2 ). Given suspicion of acute porphyria, urine porphobilinogen was measured and was found to be elevated at 188.4 mg/L (range: 0.0–2.0 mg/L). 24-hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr (range: 0.0–1.5mg/24hr). Delta-Aminolevulinic Acid (ALA) and PBGD urine tests were ordered. Since Hemin treatment was unavailable at our facility, patient was transferred to a tertiary center. Patient was treated with Hematin, and symptomatic improvement ensued ( Table 1 ).'}", "questions": ["How would you characterize the patient's abdominal pain in terms of its evolution, intensity, location, radiation, and any accompanying symptoms?"], "ground_truth_arguments": ["worsening abdominal pain", "abdominal pain was severe, generalized, non - radiating and associated with constipation"]}
{"id": "CaseReportBench:train-51", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case': \"A 27-year-old female was admitted to the hospital because of left hemiplegia and aphasia. She was 162 centimeters tall and 30 kilograms in weight. She was born after a normal pregnancy and delivery. There was no family history of neurological diseases. Motor and intellectual development was normally attained during infancy. She was hospitalized for general muscle weakness and gait disturbance when she was 6 years old. A neurologic exam showed decreased muscle tone and strength, and atrophic muscle mass. She had consistent muscle weakness, so a muscle biopsy was performed from the calf muscle when she was 8 years old. The biopsy showed mitochondrial myopathy of the pleoconial type. Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems. Follow-up procedures were performed in an outpatient clinic once or twice a year. When she was 24 years old she had sudden syncope. An magnetic resonance imaging (MRI) revealed acute infarction of the left basal ganglia and the left frontal lobe. Two years later, when the patient was 26, she had another stroke and presented with general weakness, aphagia, and dysarthria. An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia. These clinical and radiological findings suggested brain involvement of MELAS syndrome. Thus, further evaluation was done for MELAS syndrome including blood lactate and genetic analysis. The plasma lactate level was 21.8 mg/dL (normal range 4.5-19.8 mg/dL). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng/dL (normal range 0.89-1.76 ng/dL) and TSH was 0.04 µIU/mL. Levels of complement component 3 and 4 were 13 mg/dL (normal range 75-145 mg/dL) and 18 mg/dL (normal range 12-72 mg/dL) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti-double stranded DNA was 1.6 (normal range 0-6). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation: m.3303C>T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome. She was treated with supportive care and rehabilitation for a month and was then discharged. Warfarin was used during the hospital stay, but was stopped when she was discharged, because MELAS syndrome causes nonvascular infarct and there is no report about the related risk of thromboembolism. One year later, she presented with another stroke with associated left sided weakness, and was subsequently admitted to the hospital. Her vital signs were stable and there were no specific findings in chest X-rays or electrocardiography. Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25%. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 ). The patient's mental status and general condition improved after she was treated with mannitol and anticoagulation therapy. Rehabilitation and supportive care, including warfarin, were followed and maintained. The patient was discharged after a month.\"}", "questions": ["What histopathologic findings were reported from the calf muscle biopsy?", "What abnormalities were noted on the first echocardiography regarding ventricular size and wall motion?", "What acute cerebral lesions were identified on MRI when the patient was 24 years old?", "What chronic cerebral lesions and metabolic abnormalities were observed on MRI and MR spectroscopy later in the disease course?", "What laboratory results were documented, including plasma lactate, renal and electrolyte panels, thyroid function, complement levels, autoantibodies, and genetic testing?", "What findings were reported on the chest X‑ray performed during the most recent admission?", "What imaging findings were described during the latest stroke episode, including MRI, magnetic resonance angiography, and echocardiography?"], "ground_truth_arguments": ["The biopsy showed mitochondrial myopathy of the pleoconial type", "Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems.", "An magnetic resonance imaging ( MRI ) revealed acute infarction of the left basal ganglia and the left frontal lobe", "An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia", "The plasma lactate level was 21.8 mg / dL ( normal range 4.5 - 19.8 mg / dL ). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng / dL ( normal range 0.89 - 1.76 ng / dL ) and TSH was 0.04 µIU / mL. Levels of complement component 3 and 4 were 13 mg / dL ( normal range 75 - 145 mg / dL ) and 18 mg / dL ( normal range 12 - 72 mg / dL ) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti - double stranded DNA was 1.6 ( normal range 0 - 6 ). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation : m.3303C > T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome.", "no specific findings in chest X - rays", "Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25 %. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 )."]}
{"id": "CaseReportBench:train-564", "dataset": "CaseReportBench", "role": "Neurology", "document": "{'Case Report': 'The patient was a 41-year-old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age. He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure. His family history was not remarkable. He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age. Three months later, he was admitted to our hospital due to impaired consciousness and vomiting. A neurological examination showed gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities. However, no ophthalmoplegia, hearing loss, or muscle weakness were detected. His mini-mental status examination score was 15/30, and his frontal assessment battery score was 5/18. The findings from routine blood tests including blood sugar and autoimmune antibodies were normal. A laboratory examination showed slightly increased serum pyruvic acid levels (1.2 mg/dL), but his serum lactate levels were normal (14.2 mg/dL). The cerebrospinal fluid lactate (34.8 mg/dL) and pyruvic acid (1.6 mg/dL) levels were elevated. Electrocardiogram and echocardiogram were normal. Brain magnetic resonance imaging (MRI) showed bilateral cortical and subcortical high-intensity lesions on T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion-weighted imaging (DWI) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient (ADC) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H-MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ). 99m Tc-Ethylcysteinate dimer single photon emission computed tomography (SPECT) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions ( Fig. 1E ). We suspected mitochondrial encephalopathy, such as MELAS. A histopathological study of the biopsied right biceps branchii muscle revealed mild variation in the fiber size, measuring from 30 to 90 microns in diameter, which was thought to be a non-specific change. No necrotic or regenerating fibers were seen. On modified Gomori-trichrome stain, ragged red fibers (RRFs) were not observed. Succinate dehydrogenase (SDH) stain revealed no strongly SDH-reactive blood vessels. Cytochrome c oxidase staining revealed no abnormalities ( Fig. 1F ). However, the complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T>C mutation, with a level of mutant heteroplasmy of 69.5%, in the mitochondrial complex I subunit gene, MT-ND3 ( Fig. 1G ). Because his family had no clinical symptoms suggestive of mitochondrial diseases, we could not conduct a complete mtDNA sequence analysis of his family. Over a two-month period, he experienced two stroke-like episodes with simple partial seizure and vomiting. Each time the stroke-like episodes ended within four days with drip infusion of edaravone and supportive care. To control epileptic seizure, we added levetiracetam (1,000 mg/day) to zonisamide (400 mg/day) and carbamazepine (400 mg/day). Because he had not yet been diagnosed with MELAS-like encephalopathy at that time, we did not administer L-arginine. His higher brain dysfunction and myoclonus worsened with each stroke-like episode.'}", "questions": ["What neurological and psychiatric symptoms did the patient first develop in early adulthood?", "What cerebrovascular and seizure disorders were documented in the patient's past medical history?", "What motor and speech abnormalities were reported during the disease course?", "What acute neurological signs were observed on admission, specifically regarding eye movements, coordination, and myoclonus?", "Which common neurological deficits were explicitly noted as absent on examination?", "Which cognitive screening instruments were used, and what general level of performance did they reveal?", "What metabolic markers were measured in the cerebrospinal fluid, and were they reported as elevated?", "What key findings were described on brain MRI and on proton MR spectroscopy?", "What perfusion abnormalities were identified on brain SPECT imaging?", "What symptoms characterized the stroke‑like episodes experienced by the patient?", "How long did each stroke‑like episode typically last?", "What was the patient’s level of consciousness during acute events such as admission or stroke‑like episodes?", "How did higher brain dysfunction and myoclonus change over the course of the illness?"], "ground_truth_arguments": ["generalized convulsions, insomnia, and depression", "ischemic stroke at 33 years of age", "epileptic seizure with epileptic encephalopathy at 37 years of age.", "myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age.", "impaired consciousness", "gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities", "no ophthalmoplegia, hearing loss, or muscle weakness", "His mini - mental status examination score was 15/30, and his frontal assessment battery score was 5/18", "The cerebrospinal fluid lactate ( 34.8 mg / dL ) and pyruvic acid ( 1.6 mg / dL ) levels were elevated.", "Brain magnetic resonance imaging ( MRI ) showed bilateral cortical and subcortical high - intensity lesions on T2 - weighted imaging ( T2WI ) and fluid attenuated inversion recovery ( FLAIR ), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion - weighted imaging ( DWI ) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient ( ADC ) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H - MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ).", "99 m Tc - Ethylcysteinate dimer single photon emission computed tomography ( SPECT ) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions", "two stroke - like episodes with simple partial seizure and vomiting", "Each time the stroke - like episodes ended within four days", "epileptic seizure", "His higher brain dysfunction and myoclonus worsened with each stroke - like episode"]}
{"id": "CaseReportBench:train-96", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case 2': 'This patient too showed considerable hyperkeratosis of palms and soles. Intraoral examination showed more teeth present. Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds. All teeth had deep periodontal pockets and grade II mobility. Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits. On the basis of history, clinical and radiographical features a diagnosis of Papillon-Lefevre syndrome was made.', 'CASE REPORT': 'An 18-year-old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi-Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16-year-old brother also complained of similar problems. Systemic history-both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2-3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.', 'Case 1': 'Patient showed bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees. Intraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility. Orthopantomograph showed severe horizontal bone loss..'}", "questions": ["What demographic information and dental concerns are described in the case?", "What aspects of the family history are mentioned in the report?", "How is the patient’s behavior and responsiveness described during the clinical examination?", "What skin findings are described, including lesion types, associated symptoms, and distribution?", "When did the skin condition first appear, and how did its manifestations progress?"], "ground_truth_arguments": ["An 18 - year - old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi - Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16 - year - old brother also complained of similar problems. Systemic history - both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2 - 3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows."]}
{"id": "CaseReportBench:train-381", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'CASE REPORT': 'A 4-year-male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy. His birth was at full-term from an uneventful pregnancy. On detailed history the child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation. Neurological examination revealed mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child. Skeletal, dental, eye/ fundus examination and eye or limb movements were normal. Child had a normal head circumference for his age. Skin examination showed scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face. Chest radiograph and all routine hematological investigations were normal. Electroencephalogram (EEG) was normal. Patient was sent for the MRI of brain. MRI was done on 0.2 tesla Signa (GE systems, USA) MRI with T2W, T1W, FLAIR sequences in all three planes. The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All these clinical and radiological findings were diagnostic of Sjogren-Larsson syndrome.'}", "questions": ["What were the findings of the chest radiograph and the routine hematological investigations?", "Can you detail the MRI brain findings, including the signal abnormalities in the white matter and which brain structures were reported as normal?"], "ground_truth_arguments": ["Chest radiograph and all routine hematological investigations were normal.", "The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal."]}
{"id": "CaseReportBench:train-154", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case 2': 'Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady. At the dermatological examination grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region ( Figure 4 ). The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers, confirming the diagnosis of pseudoxanthoma elasticum ( Figure 5 ). Right ophthalmoscopy, retinography and angiography revealed angioid streaks ( Figure 6 ). Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal.', 'Case 1': 'Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family. At the dermatological examination, coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae ( Figure 1 ) were observed. The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis, compatible with the diagnosis of pseudoxanthoma elasticum ( Figure 2 ). Cardiological evaluation did not show changes (normal electrocardiogram and echocardiogram). Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography ( Figure 3 ).'}", "questions": ["What is the diagnosed condition responsible for the yellowish papules and the calcified, fragmented elastic fibers observed in the patients?"], "ground_truth_arguments": ["pseudoxanthoma elasticum", "pseudoxanthoma elasticum"]}
{"id": "CaseReportBench:train-34", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case Report': \"A 13-year-old male child born off a consanguineous marriage presented with complaints of red colored urine since birth, reddish brown-pigmented teeth, and excessive facial hair since 6 months of age. He also had a burning sensation and recurrent blistering over the sun-exposed areas, which healed with scarring and disfigurement of nails since 1-year of age. His birth and mental developmental history were normal. He had an asymptomatic female sibling 8 years of age, and there was no family history of similar complaints. Examination revealed a short statured male child of height 133 cm (< −3 standard deviations). Abdominal examination revealed a protuberant abdomen with hepatosplenomegaly and undescended testis on the left side. He had obvious hypertrichosis over face involving the cheek and forehead, the forearms and multiple bullae over the dorsum of hands, fingers, forearms, and feet with postinflammatory hyperpigmentation and scars over affected skin. Teeth showed brownish-red pigmentation, fluorescent under Wood's lamp. Nails were discolored. Investigations revealed anemia an Hb of 8.3 g/dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis. Urine was port wine color, which fluoresced in Wood's lamp. Porphobilinogen was not detected on Watson–Schwartz test in the urine. Ultrasonography of abdomen confirmed the hepatomegaly, splenomegaly, and the undescended testes with hydrocele on the right side. Mutation analysis was carried out for the affected child and his parents. The affected child exhibited a missense mutation in the UROS gene identified as a transversion of A to G at nucleotide 56, resulting in a substitution of tyrosine by cysteine. The patient showed a homozygous mutant profile, and the parents were heterozygous carriers for the mutation. Based on the clinical presentation with onset in early childhood of a photosensitive disorder with erythrodontia, hypertrichosis, fluorescent red urine, absence of porphobilinogen in urine, and a demonstrated mutation of the UROS gene the child was diagnosed as a case of CEP. He was managed with sun avoidance and liberal use of sunscreen administration. He was referred to the surgical center for definitive management of undescended testis. He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens (HLA) matched donor.\"}", "questions": ["What is the age of the patient at the time of presentation?"], "ground_truth_arguments": ["13 - year - old"]}
{"id": "CaseReportBench:train-197", "dataset": "CaseReportBench", "role": "Gastrointestinal-System", "document": "{'Case details': \"A 14-year-old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina ( Fig. 1 ). He was also noticed to have a low heart rate. Hence KSS was suspected. His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities. However this was not associated with breathlessness or chest pain. There were no episodes of syncope, pre-syncope or night terrors. His developmental history was normal. He had previously been evaluated at 3 years of age for recurrent episodes of vomiting. His clinical examination at that age was reported to be normal. Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non-diagnostic. Hence no metabolic diagnosis was made and he was kept on follow up. Fig. 1 Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina. Fig. 1 On examination he weighed 38 kg and his height was 148 cm. There were no dysmorphic features or congenital anomalies. His peripheral perfusion was good and all peripheral pulses were felt equally. His pulse rate was 47/minute with regular pulses and a normal volume. There was no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space. His chest was clear on auscultation and his liver was not enlarged. Clinical evaluation of the neurological system was normal. His chest x-ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits. His electrocardiogram revealed complete atrio-ventricular disassociation with an atrial rate of 100/min and a broad complex ventricular escape rhythm with a rate of 43/minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds. Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature (a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence). Fig. 2 Electrocardiogram showing evidence of complete heart block with an atrial rate of 100/minute and a broad complex escape rhythm with a ventricular rate of 43/minute. Fig. 2 As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra-Hisian rhythm he was implanted with a dual chamber transvenous pacing system (St Jude's Accent MRI system with 52 cm (atrial) and 58 cm (ventricular) St Jude Tendril MRI leads). The pacemaker was set in DDD mode with a lower rate of 50/min, a maximum sensor rate of 110/minute and an upper tracking rate of 130/minute. The procedure was uneventful. His device was interrogated regularly with no significant concerns. On follow up, his parents reported an improvement in his effort levels as well as appetite. Two years after his pacemaker implantation and two weeks after his last pacemaker clinic visit, his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive and started cardio-pulmonary resuscitation. An ambulance arrived twenty minutes later and continued resuscitation en route to the nearest hospital where he could not be revived and declared dead on arrival. An autopsy was not performed in honor of his parents' wishes.\"}", "questions": ["What episodes of vomiting were reported in the patient's early medical history?", "What observations were made about the liver size during the physical examination?"], "ground_truth_arguments": ["recurrent episodes of vomiting", "liver was not enlarged"]}
{"id": "CaseReportBench:train-310", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}", "questions": ["What were the birth details of the proband, including gestational term, parental consanguinity, and mode of delivery?", "What was the status of the pregnancy and were any gestational complications reported?", "What metabolic abnormality was observed on the day of delivery and what were the measured blood glucose levels?"], "ground_truth_arguments": ["The proband was born full - term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL."]}
{"id": "CaseReportBench:train-290", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What age category (e.g., pediatric, adult, elderly) does the patient fall into at the time of presentation?"], "ground_truth_arguments": ["48 - year - old"]}
{"id": "CaseReportBench:train-29", "dataset": "CaseReportBench", "role": "IEM-Treatment", "document": "{'Patient Consent': 'Patient consent was obtained.', 'Case Presentation': 'A 24-year-old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease (CKD) was referred for preconception counseling. Cystinosis was confirmed by an elevated leucocyte cystine level in infancy. Early diagnosis, made possible by cystinosis in an older sibling, and good treatment adherence contributed to delayed kidney disease progression. Electrolyte abnormalities secondary to Fanconi syndrome were treated with daily supplemental dosages of potassium 96 mmol, phosphate 25.2 mmol, and sodium bicarbonate 53.6 mmol. There were no overt extra-renal complications apart from mild photophobia. Her average prepregnancy urine protein-to-creatinine ratio was 132 mg/mmol, α1-microglobulin-to-creatinine ratio was 30.7 mg/mmol, and estimated glomerular filtration rate (eGFR) was 89 ml per minute per 1.73 m 2 . On confirmation of pregnancy, losartan and cysteamine were discontinued. Low-dose aspirin was initiated for the prevention of pre-eclampsia. As expected, proteinuria and eGFR increased during pregnancy. 8 Blood pressure remained normal with no evidence of gestational hypertension or pre-eclampsia. Daily electrolyte supplementation increased to potassium 128 mmol and phosphate 33.6 mmol, with no increase in the dose of sodium bicarbonate. Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein. The pregnancy was complicated by recurrent urinary tract infections (UTIs) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia. After treatment of the complicated UTI, prophylactic oral antibiotics were administered for the remainder of pregnancy without UTI recurrence. She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes. The infant was admitted to the neonatal intensive care unit for 23 days. Cysteamine was reinitiated immediately after delivery and enalapril was initiated at 2 weeks postpartum. The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1-microglobulin-to-creatinine ratio and eGFR were stable ( Figure 1 ). Figure 1 Urinary proteins and eGFR at baseline, during pregnancy and postpartum. eGFR, estimated glomerular filtration rate. While breastfeeding, her delayed-release cysteamine dosage was 675 mg twice daily (0.84 mg/m 2 /d) compared with her prepregnancy dosage of 825 mg twice daily (1.06 mg/m 2 /d). The cysteamine dosage was reduced during breastfeeding as a precaution because of the lack of lactation safety data. She exclusively breastfed for 4 months and discontinued at 5 months. The cysteamine dosage subsequently stabilized at 750 mg twice daily (0.95 mg/m 2 /d). Breastmilk samples were collected and analyzed ( Table 1 and Supplementary Methods ). The calculated relative infant dose was 0.4%. The predicted infant cysteamine dose over 24 hours was 0.52 mg. Infant cysteamine levels were not measured. The infant had normal growth and development at 18 months and a normal leucocyte cystine level. Table 1 Breastmilk cysteamine concentration relative to dose of delayed-release cysteamine bitartrate at steady state Time postdose (h) Breastmilk cysteamine concentration (mg/l) 0 0.12 2 0.76 4 1.87 6 0.51'}", "questions": ["At what point after delivery was cysteamine therapy resumed?"], "ground_truth_arguments": ["Cysteamine was reinitiated immediately after delivery"]}
{"id": "CaseReportBench:train-468", "dataset": "CaseReportBench", "role": "Patient-History", "document": "{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}", "questions": ["What observations were made regarding the infant's subcutaneous tissue during early infancy?", "Were any concerns about weight gain noted during the early health examinations?"], "ground_truth_arguments": ["apparent reduction of the subcutaneous adipose tissue at 1 mo of age", "Poor weight gain was seen during a health checkup at 3 mo of age"]}
{"id": "CaseReportBench:train-337", "dataset": "CaseReportBench", "role": "Age-of-Onset", "document": "{'Case Report': 'At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine. She was born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively. As a 3-week-old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed. At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day. Physical examination revealed multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back. The spleen was of normal size and physical and intellectual development was normal. Again, moderate hemolytic anemia was also found (red blood cells: 3.68 × 10 6, hemoglobin: 10.6 g/dl, hematocrit: 33.0%, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G/DL, platelets 124 × 10 3 ml, white blood cells: 3.6 × 10 3, reticulocytes: 58 (5-15)), but did not require a blood transfusion. Further laboratory investigations were as follows: urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal. Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable. Now, aged 14 years, the severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands. Using all available measures to protect herself from the sun (hat, eyeglasses, cosmetic camouflage, and long sleeves) has not succeeded in protecting her from the mutilating effects of sun. This has caused scarring of her skin at sun-exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp. In addition, she has restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust. Moderate hypertrichosis on the back of the neck was also noted and her teeth have progressively stained brownish-red. The results of the biochemical investigations are summarized in Table 1 . Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High-pressure liquid chromatography of the urine demonstrated 85% of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617. These results confirmed a diagnosis of CEP. Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T>C (p.Cys73Arg) in exon 4 and c.683c>T (p.Thr228Met) in exon 10. These missense mutations have previously been described, where the patient had a moderate to severe phenotype.'}", "questions": ["At what age (e.g., weeks, months) did the patient first experience hemolytic anemia that required a blood transfusion?"], "ground_truth_arguments": ["3 - week - old"]}
{"id": "CaseReportBench:train-619", "dataset": "CaseReportBench", "role": "Genitourinary-System", "document": "{'Case Report': 'A 20-year-old Turner syndrome (TS) patient with Neurofibromatosis 1 (NF1) and Tuberous sclerosis complex (TSC) was apparently normal till five years of age. She later started developing small skin lesions of the size of pin head over the face which gradually increased in size and number. There was also a swelling over the left forearm, about the size of a marble, which gradually increased to attain the size as shown in Figure 1a . The developmental milestones were within normal limits and the patient had attained menarche at 12 years of age with regular menstrual cycles with no history of seizures. Table 1 presents the phenotypic observation of the patient, in comparison with standard clinical manifestation. The expression level varies for all three disease conditions. Clinical investigations revealed that the girl had typical features of TSC in the form of Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café-au-lait spots ranging in size from 1.5cm to 4cm scattered all over the body confirmed NF1. Along with NF 1 and TSC, Turner features were evident with short stature, webbing of neck, low hair line, low set ears, high arched palate and cubitus valgus deformity. About 10-20% of Turner syndrome girls had spontaneous breast development and a small percentage may have menstrual periods. Pregnancies have been reported for spontaneously menstruating patients. The patient studied had also shown menstruation regularly with normal breast development, normal uterus and ovaries in pelvic ultrasound. Chromosomal analysis of the proband was carried out on peripheral blood lymphocyte culture by using the standard protocol of Seabright. with slight modifications. G-banded metaphases were screened by using a Leica DMRA2 research microscope. A total of 100 well banded metaphase plates were analyzed and karyotyped according to the International System for Human Cytogenetic Nomenclature-2005. Chromosome analysis of the patient confirmed with 45, XO Karyotype. An informed consent was obtained from the affected family members, before their inclusion in the study. Pedigree of the proband family revealed that there was no parental consanguinity. At the conception of the proband, the ages of the mother and father were 45 and 50 years respectively. There was no history of miscarriage or birth defects but her elder brother also had similar skin lesions over the face, which appeared at the age of seven years with Adenoma Sebaceum, Shagreen patch revealed the appearance of TSC.'}", "questions": ["Can you describe the patient's overall pubertal milestones, including the onset of menstruation?", "What observations were noted regarding the patient's secondary sexual characteristics?"], "ground_truth_arguments": ["attained menarche at 12 years of age with regular menstrual cycles", "patient studied had also shown menstruation regularly with normal breast development"]}
{"id": "CaseReportBench:train-561", "dataset": "CaseReportBench", "role": "Age-at-Presentation", "document": "{'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'CASE REPORT': \"A 27-year-old male, presented to our clinic with a history of foreign body sensation in both eyes for the previous 2 years. He had a history of blistering skin lesions on the photo-exposed areas of the body for the past 12 years. At first, blisters started developing over the lower extremities and then gradually involved upper extremities and face. There was also a history of hyper-pigmentation and scarring of the photo-exposed areas of the body. He developed severe pain in the fingers of both hands 1-year prior presentation. He complained of the passage of red colored urine for the past 1 year. There was no history of acute abdominal pain and no family history of the similar phenomenon was found. Striking features on physical examination were a pinched up nose, scarring over the lips, nose, hands, and resorption of distal phalanges of all the fingers in both hands except onycholysis of the smallest digits. Onycholysis was present on all the toes. The remainder of the systemic examination was noncontributory. The patient's uncorrected visual acuity was 20/40 in both eyes. Best corrected visual acuity was 20/20 in both eyes with a correction of –0.5 × 115° in the right eye and –1.25 × 80° in the left eye. Air-puff tonometry measured intraocular pressure of 14 mm-Hg bilaterally. The fundus examination was unremarkable. Slit-lamp examination indicated scleral necrosis in the interpalpebral area of both eyes that was more pronounced temporally compared to nasally. Temporally, it was 4 mm × 3 mm in the left eye and 3 mm × 3 mm in the right eye. Nasally, minimal scleral necrosis was seen with overlying fibrosed conjunctiva in both eyes. Mild conjunctival scarring was present in the temporal necrosed part of the right eye. In the left eye, the temporal necrosed part was devoid of conjunctival tissue, a frill of conjunctival tissue was present at the margin of the necrosed area. Conjunctiva and sclera in the covered area appeared to be normal. Infiltrations were seen in the peripheral cornea of both eyes near the limbus with temporal and nasal involvement. Fluorescein staining indicated normal epithelium. Schirmer's test 1 was 8 mm in the right eye and 10 mm in the left eye. These symptoms were suggestive of porphyria. Laboratory testing based on the definite pattern of accumulation and hyperexcretion of porphyrins and porphyrin precursor is the most effective measure for diagnosis and typing of porphyrias. Exact porphyrin isomer identification requires sophisticated equipment such as high-performance liquid chromatography which is unavailable at our center and in most hospitals in the developing countries. Hematological tests reported hemoglobin, 9.8 g/dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase (423U/l) and mild increase in serum bilirubin (1.8 mg/dL). Ultrasonography of the whole abdomen showed splenomegaly (17 mm). These features are suggestive of hemolytic anemia. The treatment involved complete avoidance of sunlight and use of dark goggles. The patient was prescribed topical cyclosporine 0.5% eye drop 3 times a day and ocular lubricant was prescribed for both eyes. We planned a full-thickness scleral patch graft with amniotic membrane transplant in the necrosed region. The patient was advised to return for periodic follow-up to our cornea clinic.\"}", "questions": ["What is the patient's age at the time of presentation?"], "ground_truth_arguments": ["27 - year - old"]}
{"id": "CaseReportBench:train-393", "dataset": "CaseReportBench", "role": "Confirmed-Diagnosis-IEM", "document": "{'Case Presentation': \"Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment. A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5 th percentile), weight 3000 g (<5 th percentile), and head circumference 36.5 cm (5–10 th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance. Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative. The laboratory tests were as follows: serum sodium 102 meq/lit and serum k + level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1 . Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern. Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed. On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25 th percentile), weight 9.5 kg (10–25 th percentile) and head circumference 46 cm (25 th percentile); her neurodevelopment was appropriate for age.\"}", "questions": ["What definitive diagnosis was established for the infant based on the clinical presentation and laboratory findings?", "Which specific congenital disorder of steroidogenesis was confirmed in this patient?"], "ground_truth_arguments": ["congenital adrenal hyperplasia ."]}
{"id": "CaseReportBench:train-255", "dataset": "CaseReportBench", "role": "Laboratory-and-Imaging", "document": "{'Case report': \"A 48-year-old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word-finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness. Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years. Computed tomography (CT) revealed a hypodense lesion within the left temporal lobe (edema) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging (MRI) demonstrated left temporal lobe diffusion signal abnormality and fluid-attenuated inversion recovery (FLAIR) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient (ADC) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 ). Clinically, her symptoms initially stabilized, but in the following week, the patient's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity. Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography (PET) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol/L. Serum lactate was elevated to 4.6 mmol/L. Serum inflammatory markers (dsDNA, anti-Hu, anti-Ri, anti-Yo, SS-A, SS-B, C3, C4) were normal. On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic–clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe. Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain ( Fig. 5 ). A clinical diagnosis of MELAS syndrome was made. The patient recovered without further complications on anticonvulsants and high-dose intravenous arginine then oral citrulline at 0.5 mg/kg. At 2-month follow-up, her cognition including language and activities of daily living had greatly improved. Genetic testing of patient's serum confirmed m.3243 A→G mutation (heteroplasmy 22%) in the MT-TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome. A detailed 3-generation family history revealed no known neurologic, muscular, cardiac, or vision problems. Genetic counseling is ongoing.\"}", "questions": ["What were the initial CT and MRI findings, including lesion location, imaging characteristics, contrast enhancement, and ADC signal?", "What did the follow‑up MRI reveal about changes in the left temporal lesion and any new cortical abnormalities, what were the general findings on PET regarding metabolic activity in the affected regions, and were lactate levels elevated in cerebrospinal fluid and serum, along with the overall status of inflammatory markers?", "What did the later MRI demonstrate about the extension of the occipital lesion and what did MR spectroscopy show regarding lactate peaks throughout the brain?", "What genetic abnormalities were identified that support a diagnosis of MELAS syndrome, including the affected mitochondrial gene?"], "ground_truth_arguments": ["Computed tomography ( CT ) revealed a hypodense lesion within the left temporal lobe ( edema ) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging ( MRI ) demonstrated left temporal lobe diffusion signal abnormality and fluid - attenuated inversion recovery ( FLAIR ) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient ( ADC ) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 )", "Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography ( PET ) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol / L. Serum lactate was elevated to 4.6 mmol / L. Serum inflammatory markers ( dsDNA, anti - Hu, anti - Ri, anti - Yo, SS - A, SS - B, C3, C4 ) were normal.", "Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain", "Genetic testing of patient 's serum confirmed m.3243 A→G mutation ( heteroplasmy 22 % ) in the MT - TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome"]}