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 3 was a 14-year-old boy. He was born via normal spontaneous vaginal delivery (NSVD) without complication at the gestational age of 36 weeks, with birth weight of 3.2 kg. C3 carnitine level elevation (37, reference: < 4.1) was detected in the expanded newborn screening program. His urine organic acid analysis confirmed PPA. His blood gas and blood ammonia levels were normal. The fibroblast carboxylase assay revealed reduced propionyl-CoA carboxylase (PCC) activity [9 pmol/min/mg protein (reference: > 91 pmol/min/mg)], normal methylcrotonyl-CoA carboxylase (MCC) activity [55 pmol/min/mg protein (reference: > 31 pmol/min/mg)], and normal pyruvate carboxylase (PC) activity [124 pmol/min/mg protein (reference: > 71)]. Propionyl carboxylase assay using biotin-supplemented culture medium showed that he was non-responsive to biotin. He was fed breast milk exclusively and an unrestricted normal regular diet. However, at 23 months of age, he was hospitalized for metabolic decompensation and hyperammonemia following rotavirus gastroenteritis. Special formula for PPA was introduced after that. The patient was not compliant with the PPA formula because of its taste. He was admitted to the hospital 12 times due to metabolic decompensation (i.e. metabolic acidosis and hyperammonemia) at 23 months of age. The unusual clinical presentation was recurrent headache, which was relieved by intravenous glucose/electrolyte infusion. At 13 years, he was diagnosed with Osgood-Schlatter disease. At 14 years of age, ophthalmologic evaluation revealed Avellino corneal dystrophy. He experienced diabetic ketoacidosis, which was associated with weight loss. His blood glucose level was 2018 mg/dL and C-peptide level was 0.87 ng/mL (reference: 0.81–3.86 ng/mL). His autoantibody profile was as follows: islet cell antibody (Ab)-negative, insulin Ab-negative, and anti-GAD Ab level < 0.11 (reference: ≤ 1.00 U/mL). Insulin was administered to the patient, after which he became compliant with the PPA special formula for diet control (Table ). His long-term metabolic profile revealed glycine level of 261–314 µmol/L (normal range: 158–302 µmol/L), significantly elevated glutamine level of 1169–1545 µmol/L (normal range: 360–740 µmol/L), and small amounts of 3-hydroxypropionic acid, propionyl glycine, and methyl citrate. His amylase level had always been normal at 81–90 U/L (reference: 28–100 U/L) during our long-term follow-up.