A 3.5-year-old girl was transferred to our institution from a local hospital with abdominal pain and bilious vomiting for further investigation and management. The child was diagnosed with isovaleric acidemia in the neonatal period, because there was a positive family history of a sibling death from this inherited disorder. Hence, measurement of elevated concentrations of isovalerylglycine in urine and of isovalerylcarnitine in plasma by mass spectrometry [] was performed after birth; then, isovaleric acid CoA dehydrogenase deficiency was confirmed by assaying its enzymatic activity in cultured skin fibroblasts [].\nThe child was admitted to the local hospital two days ago because of new-onset upper abdominal pain. Although she was unable to describe the nature and character of the pain, it was not severe enough to require analgesics. One day prior to her admission to us, she developed vomiting that eventually became bilious.\nThe patient who had normal growth and development was on oral L-carnitine supplementation since infancy. Beside that, she was not receiving any other medications. Her family history was negative for pancreatitis. On admission to us, she was afebrile with normal vital signs. On physical examination, there was moderate upper abdominal tenderness without rebound, while she had normal bowel sounds and no organomegaly. Laboratory studies on admission revealed the following: leukocytes 10,110/μL, hemoglobin 14 g/dL, hematocrit 37.2%, platelets 169,000/μL, glucose 185 mg/dL (normal < 100 mg/dL), urea 26 mg/dL, creatinine 0.4 mg/dL, sodium 133 mEq/L, potassium 3.6 mEq/L, chloride 103 mEq/L, AST 34 U/L, ALT 22 U/L, LDH 426 U/L (normal < 280 U/L), albumin 4.3 g/dL, total bilirubin 0.7 mg/dL, direct bilirubin 0.2 mg/dL, γ-GT 16 U/L, triglycerides 80 mg/dL, calcium 10 mg/dL, and amylase 536 U/L (normal 40–140 U/L). Arterial blood gases showed the following: pH 7.55, pCO2 21 mmHg, pO2 133 mmHg, HCO3 23 mmol/L, and base deficit 3.8 mmol/L. The anion gap was estimated at 7. A coagulation profile and a urine analysis were normal.\nDue to the bilious nature of vomiting, an abdominal ultrasound () was obtained that showed a notably enlarged and edematous pancreas, along with the presence of peripancreatic exudates that were extending bilaterally towards the anterior paranephric spaces and towards the right colon. The wall of the duodenum was also diffusely edematous. No gallstones were seen, the bile duct was not distended, and there was no sludge in it, while the liver, spleen, and appendix were visualized without echomorphologic abnormalities.\nSince the goal of management of acute pancreatitis is to achieve analgesia, adequate rehydration, and organ rest, the child was managed with discontinuation of oral feedings, placement of a nasogastric tube, intravenous hydration with 5% dextrose with electrolytes, and administration of intravenous ranitidine and of L-carnitine, 500 mg every 8 hours, that is, approximately 100 mg/kg/day.\nThe patient's clinical course was uncomplicated. Serum amylase normalized (84 U/L) on the 4th hospital day. She was fed with a low-fat and protein diet on the 6th hospital day. On the same day, the intravenous fluids were discontinued. Two follow-up ultrasonographic examinations on the 3rd and 5th () hospital days showed progressive but rapid resolution of the pancreatic edema and of the peripancreatic exudates. Due to substantial clinical improvement, with complete disappearance of the abdominal pain, the child was discharged home without any complaints on the 8th hospital day. She continued to do well, two months after hospital discharge.
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.