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 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 ).