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 ).
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.