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.
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.