Case 1 was a 20-year-old man with MMA. He was born via cesarean section because of placenta previa at gestational age of 37 weeks with birth weight of 2.7 kg. Due to positive family history (his brother had MMA), he underwent metabolic investigation. His metabolic evaluation revealed blood ammonia level of 400–500 mg/dL and elevated C3 carnitine level (48.8; reference range, < 4.1). The methylmalonic acid level in urine was 1617 µg/mg Cr, and elevation in plasma glycine (415 µmol/L) and alanine (978 µmol/L) levels were noted. Cobalamin (Cbl) incorporation study of 14C-propionate showed lack of response to Cbl (i.e. mut0) and slightly low response to adocobalamin (AdoCbl). Molecular investigations revealed a compound heterozygous c.1105C > T(p.R369C), p.G94Q mutation. He was fed with special formula (Propiomex), regular infant formula, low-protein food, and L-carnitine supplement (100 mg/kg/d). His developmental evaluation at 20 months of age showed a mild delay. Prior to 5 years of age, blood urea nitrogen (BUN) and creatinine were in the normal range (BUN 6.6–12.3 mg/dL /creatinine 0.7–0.8 mg/dL). However, after 5.5 years of age, his renal function slowly deteriorated, showing a BUN level of 16.2–29.2 and creatinine level of 0.81–1.02. He was hospitalized multiple times due to metabolic decompensations (acidosis, dehydration, and hyperammonemia) after trivial infections or skipping of the special formula. At 6 years of age, his eye sight deteriorated progressively and he became legally blind due to optic atrophy by 10 years of age. He received growth hormone treatment for metabolic induction to anabolism and improvement of his short stature. At 15 years of age, he experienced vomiting and abdominal pain due to pancreatitis. His metabolic status became unstable; he was hospitalized more than 7 times with pancreatitis (Table ). At this time, he began to experience hand tremors due to his metabolic condition. After recurrent pancreatitis at 19 years of age, he showed glucose intolerance. By the age of 20 years, he developed DM, requiring insulin injection. His most recent metabolic crisis was accompanied by severe metabolic acidosis (pH 6.8), liver dysfunction (aspartate aminotransferase (AST) 245 IU/L, alanine aminotransferase (ALT) 316 IU/L), hyperventilation, hemorrhagic gastritis, and left pleural effusion. His pancreatic amylase and lipase levels were > 4000 U/L. He was put on continuous renal replacement therapy for 3 days. During the metabolic crisis, he experienced seizures and hand tremors, although the results of brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were normal. The abdominal computed tomography (CT) showed necrotizing pancreatitis and follow-up ultrasound after 1 month of pancreatitis showed a pancreatic pseudocyst. His renal function progressively deteriorated, showing a BUN level of 40.1–60 mg/dL, Cr level of 2.04–2.81 mg/dL, and estimated glomerular filtration rate (eGFR) level of 43.7 mL/min/1.73 m2. His metabolic parameters were as follows: pH, 7.30–7.31; HCO3 level, 11.2–20.6; methylmalonic acid level, 1768–3861 µg/mg Cr; glycine level, 625–1187 µmol/L (normal range: 158–302 µmol/L); alanine level, 508–825 µmol/L (normal range: 185–537 µmol/L). His ferritin levels were 280–581.53 ng/mL (normal range: 50–200 ng/mL). His current weight is 46.1 kg and height is 164 cm. He has recovered completely from pancreatitis, and his glucose levels are being controlled using insulin (Table ).
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.