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.
Case 6 was a 35-year-old woman who was confirmed to be blind and diabetic. She was born at full term via NSVD to a 21-year-old mother (G2P1 SAB) with a birth weight of 3.73 kg. She had tunnel vision, myopia, and night blindness at the age of 5 years. At the age of 7, she was diagnosed with juvenile-onset diabetes. She had menarche when she was 16 years old. She was evaluated metabolically at the age of 34 and high ornithine levels were detected in her blood and urine. Hyperornithinemia/gyrate atrophy was confirmed. She was legally blind, but had been working with constricted visual field at a daycare center. She had normal chromosomes (46, XX). The pancreatic autoimmune panel test was negative for the GAD protein and islet cell antibody; however, a high titer of anti-insulin antibodies was observed, which might be due to insulin therapy. Her vital signs, including blood pressure (110/70 mm Hg), were stable. Her weight was 57.1 kg (50th percentile), height was 156 cm (10th percentile), and HC was 54.5 cm (25–50th percentile). She looked relatively healthy and had a round face. Physical examination showed short stature and sparse light and dark hair. Her lower thoracic cage was prominent. Her lungs were clear to auscultation and heart sounds were normal without murmurs. Regarding the extremities, she had short limbs, thick and short fingers, missing knuckles of the 4th fingers, abnormally long 2nd and 4th toes, pitting edema, and mildly short Achilles tendons. She had subcutaneous nodules on both legs, lipodystrophy on the injection sites of the abdomen, and brisk DTR. In addition, her visual field was extremely constricted and her fundi showed abnormal pigmentation, sparing a small proportion of the retina. Ophthalmologic examination revealed isocoric pupils, clear corneas, pale fundi, and thin retinal vessels; she also had limitations of extraocular muscle movements in all directions, with nystagmus. Plasma amino acid analysis showed ornithine levels of 756–900 µmol/L (reference: 106 µmol/L). After the diagnosis of gyrate atrophy of the choroid and retina associated with hyperornithinemia, she was fed a low-protein diet (Table ). During the follow-up, she did not have pancreatitis (Table ).