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 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 ).