An 8-year-old male patient admitted to our pediatric emergency clinic due to acute abdominal pain, nausea and non-bilious vomiting. The pain was severe, intermittent and localized in the umbilical region. There was no history of trauma and chronic drug use.\nHe had been investigated due to hypotonia in the neonatal period but no etiological factor had been determined. At the age of six years, he was performed cranial magnetic resonance imaging due to mild mental retardation and speech impairment and reported to be normal. Additionally; he had been hospitalized and treated for AP attack in our pediatric gastroenterology clinic two years previously. No causative factor was determined for the AP attack. Thereafter; he had admitted two times to another medical center due to recurrent vomiting and abdominal pain attacks. No aggravating factor was determined by the physicians for the abdominal pain attacks.\nThird-degree parental consanguinity was present in family history. Our patient was the mother's third pregnancy (gravidity 6, parity 5, alive 4, and miscarriage 1). Two siblings had idiopathic epilepsy.\nAt physical examination, his appearance was lethargic. His body weight was 22 kg (10-25 percentile) and height was 132 cm (50-75 percentile). At laboratory analysis; complete blood count, electrolyte, liver-kidney function tests, lipid levels, lactate were within the normal levels. The initial ammonia level was 69 µmol/L (normal range, 16-53 µmol/L). The mild hyperammonemia improved spontaneously on second day. The blood gas analysis was normal (pH, 7.41; PCO2, 38 mmHg; PO2, 93 mmHg; HCO3, 21 mmol/L; SPO2, 98; BE, 1.2 mmol/L). Serum amylase and amylase clearance were 1,442 U/L (normal range, 25-90 U/L) and 6% (normal interval, <5%), respectively. Abdominal ultrasonography revealed increased pancreatic tail echogenecity and size with perisplenic and pelvic free fluid. The patient was hospitalized for the second time with a diagnosis of AP on the basis of clinical, laboratory and radiological findings. Oral nutrition was discontinued and the patient was started on somatostatin, intravenous fluid and antibiotics. The clinical and laboratory findings of the patients improved on the sixth day.\nMagnetic resonance cholangiography performed due to recurrent AP attacks and revealed minimal dilation of 3 mm at the widest point in the main pancreatic duct (normal interval, 2-3 mm). There was no pancreatic stone, congenital malformation or other anomaly.\nMetabolic tests including tandem mass spectrometry and urinary organic acids performed due to mental retardation, family history, consanguinity and recurrent attacks (abdominal pain and vomiting). There were an increase in isovaleric acid and its derivatives in urinary organic acids (isovaleryl-glycine >20×normal upper limit), an increase in C5 isovaleryl-carnitine (3.38 µM; normal upper limit, 0.47) and a decrease in C0 free carnitine (5.43 µM; normal lower limit, 7.5) and C3 propionyl-carnitine (0.48 µM; normal lower limit, 0.55) at tandem mass spectrometry which analyzed in serum data. A diagnosis of IVA was made based on metabolic test results. Molecular genetic analysis revealed a homozygous mutation of (p.E117K [c.349G>A]). The patient was started on protein and leucine-restricted diet (1.5 g/kg), glycine (200 mg/day) and carnitine (100 mg/kg). We have been monitoring the patient for 8 months and no AP attacks have occurred following therapy.\nMolecular genetic analysis of parents and a healthy sibling were studied because of parental consanguinity history and revealed a heterozygous mutation of (p.E117K [c.349G>A]). The other siblings with epilepsy could not studied ().
Case 5 was a 15-year-old boy with cerebral palsy. He was born via NSVD at full term. He showed normal growth and development until 40 months of age, which was when he had seizures followed by fever of unknown origin. He underwent a day-long fasting for sonogram, which resulted in acute liver enlargement and elevated liver enzyme levels. The sonogram showed fatty liver and hepatomegaly. Following the fasting, he had cerebral palsy with spasticity. The acylcarnitine profile showed elevated free carnitine levels, no ketones in urine, and generalized aminoaciduria. Urine acylglycine analysis revealed a propionyl glycine level of 3.81 (reference: < 1.93), and urine organic acid analysis revealed hypoketotic hypoglycemia and 3-methylglutaconic aciduria during a metabolic crisis. He experienced periodic pseudo gut paralysis, requiring metronidazole treatment. Muscle biopsy showed normal mitochondria, although the number of mitochondria was low. At 10 years of age, he entered an unresponsive semi-comatose state following poor oral food intake for over 6 days, which was accompanied by marked hepatomegaly, severe dehydration, and pancreatitis. His liver enzymes were elevated as follows: AST, 4428 U/L; ALT, 2532 U/L; however, his bilirubin level was normal (0.2–0.3 mg/dL). At the same time, his renal function was considerably impaired (BUN level, 120 mg/dL (reference: 18 mg/dL); Cr level, 2.6 mg/dL; lactic acid level, 2.9 mmol/L; NH3 level, 200–300 mmol/L). Other laboratory findings showed the following: sodium level, 140; chloride level, 107 mmol/L; phenylalanine level, 720 (normal range: 39–76); free carnitine level, 80.2 (reference: ≤ 50); LDH level, 456 U/L (normal range: 100–190 U/L); CPK level, 446 mg/dL (normal range: 21–232 mg/dL); lipase level, 493–13,978 U/dL (normal range: 10–140 U/dL); amylase level, 122.0–808 U/dL (normal range: 25–125 U/dL) (Table ). Abdominal CT scan showed edematous changes and enlarged pancreas. Pancreatitis was alleviated in 2 weeks by supportive treatment involving the administration of 10% dextrose electrolyte solution. His extra-pancreatic manifestations were pleural effusion, pneumonia, and scoliosis of the T-L spine. At 11 years of age, he had status epilepticus after prolonged inadequate oral food intake because of parental refusal to undergo gastrostomy tube placement. He again experienced liver dysfunction and progressive hepatomegaly. Brain MRI revealed severe brain atrophy with dilatation of ventricles and prominent sulci. After recurrent aspiration pneumonia, pseudo gut paralysis, and liver dysfunction, he died of a cardiac arrest at the age of 15 years.