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 ().
On January 27, 2014, a 4-year-old boy was admitted owing to a second episode of pancreatitis at a general hospital and experienced abdominal pain and vomiting for 3 days. The first episode of acute pancreatitis occurred 1 year before. He was referred to our children's hospital for further work-up and treatment. At arrival, he was fully conscious, and his symptoms were much improved. Laboratory tests revealed a hemoglobin level of 13.2 g/dL, white blood cell count of 8,720/µL, and platelet count of 334,000/µL. Amylase and lipase levels were 175 and 465 U/L (normal range, 22–80 and 0–60 U/L) respectively, which were improved from 773 and 1,969 U/L at a regional hospital 2 days prior. Coagulation tests revealed normal. He had metabolic acidosis with HCO3− level of 8 mmol/L, and a base deficit of 16 mEq. Urinalysis revealed severe ketonuria. Fasting blood glucose level was 65 mg/dL, and ammonia level was 59 μmol/L. Magnetic resonance cholangiography revealed a diffusely swollen pancreas without parenchymal necrosis and duct anomaly (). The patient received TPN consisting of all macronutrients, including amino acids. However, metabolic acidosis, intermittent vomiting, and decreased activity persisted. On the seventh day of hospitalization, he was transferred to the intensive care unit because of a sudden metabolic crisis with generalized tonic convulsion lasting for 2 minutes, with prolonged postictal drowsiness. His blood pressure decreased to 81/42 mmHg. Ammonia increased to 175 μmol/L. Amylase and lipase levels were 168 and 413 U/L, respectively. Platelet count was 86,000/μL, and PT and aPTT were not measurable (). Fibrinogen and antithrombin levels decreased to 114.5 mg/dL and 68.4%, respectively. D-dimer level increased to 1.6 mg/L, and disseminated intravascular coagulation was evident. Azotemia was not observed, and calcium decreased to 5.7 mg/dL.\nThe CT scan of brain was unremarkable. The chest X-ray showed signs of pulmonary edema, and the patient's oxygen saturation decreased to < 90%. The electrocardiogram showed tachycardia at a rate of 150 beats/min, and the QTc interval prolonged to 0.527 seconds. The echocardiogram revealed decreased left ventricular contractility, with an ejection fraction of 41.0% and fractional shortening of 19.8%, and digoxin was administered to treat toxic myocarditis. Intensive care was applied for myocarditis, hyperammonemia and disseminated intravascular coagulation caused by metabolic crisis. All-in-one TPN fluid was changed to TPN fluid without amino acid. In the metabolic disease work-up, tandem mass spectrometry showed an increase in C3 carnitine, indicating the possibility of PA and methylmalonic acidemia. Increased glycine level in plasma amino acid testing and increased 3-hydroxypropionic acid, methylcitric acid, and propyl glycine levels in urine organic acid testing suggest PA. Molecular genetic analysis revealed compound novel heterozygous mutations of PCCB gene: c.1316A>G (p.Tyr439Cys) and exon 8 deletion. Both mutations were predicted to be deleterious by in silico analysis database, SIFT, PolyPhen-2 and Mutation Taster. The patient's condition and all laboratory test results improved to reach the normal values after protein administration was stopped and replaced with supportive care, including methylmalonic propionic acidemia (MPA) formula, metronidazole, and antioxidant cocktail including biotin, vitamin E, L-carnitine. Five years of follow-up until now, the patient experienced several additional episodes of recurrent pancreatitis even after the administration of MPA formula and restriction of protein supplementation. After regular prophylactic use of metronidazole (weekly dose every month), no incidence of pancreatitis has occurred. Growth and development of the patient occurred normally.\nThe patient's legal guardians provided written informed consent.