B₁₂‐unresponsive methylmalonic aciduria in a female infant

Abstract

The first child (D.M.) of healthy, unrelated parents had birthweight 2700 g and Apgar score 9. She did well while exclusively breast-fed but began to vomit without apparent precipitating cause during her sixth month of life. She was then hospitalized in life-threatening condition and treated with intravenous fluids and sodium bicarbonate. Recovery was slow.After 40 days of apparent clinical well-being, the infant was referred to the Department of Pediatrics of the University of Bari because of fever, dehydration and persistent vomiting. Physical examination revealed a small, drowsy infant with Kussmaul-type respirations and marked muscular hypotonia. Her weight, length and head circumference were below the third percentile. The liver was moderately enlarged. No abnormal odour was noted apart from the smell of acetone in her breath. Acid-base parameters showed severe metabolic acidosis (blood pH 7.00; Pcoz t4mmHg: olasma bicarbonate 4 mmol/l; base excess -24 mmol/1) and a strong ketoaciduria was present. Blood ammonia, glucose, lactate and serum immunoglobulins were within normal limits. Blood. count was normal; no neutropenia or thrombocytopenia were noted. By thin-layer chromatography, the blood and urine amino acids, including glycine and methionine, were normal. Homocystine was not detectable. A colorimetric screening test for urinary methylmalonate (Giorgio and Luhby, 1969) was strongly positive. Radiograms of skull, chest and long bones showed no abnormalities initially.Despite vigorous therapy (5% glucose infusion with sodium bicarbonate and i.m. cobalamin) the child fell into a coma. Then peritoneal dialysis was performed for 48 h. Following these measures progressive clinical improvement was noted, while metabolic acidosis and ketonuria disappeared. Muscular hypotonia, failure to thrive, poor feeding with recurrent vomiting and acidosis were prominent findings during the subsequent period of hospitalization. Methylmalonic aciduria was constantly present, but no sign of serious neurological impairment was observed. A protein-restricted diet (0.5 g kg-~ day-t) was started and i.m. cobalamin (I000 ~tg/day) was given for 10 days: acidosis regressed somewhat, but urinary methylmalonate excretion persisted unmodified. The failure to gain weight and the prompt onset of oedema resulting from protein malnutrition obliged us to stabilize the infant at a higher protein level ( l-1.5 g kg-~ day-t). After 2 months of hospitalization she was discharged weighing 5700 g. Vitamin B~_~ (hydroxycobalamin twice a week i.m.) at a dose of 1000 lag and a low-protein diet were given at home. In addition, the parents were advised to monitor ketonuria daily with Acetest tablets, a strongly positive reaction indicating the need for readmission. Two weeks later the child was readmitted with acidosis and lethargy, respiratory infection having precipitated a recurrence of symptoms. Treatment with intravenous fluids, sodium bicarbonate and antibiotics was started and daily intramuscular injections of 5'-deoxyadenosyl cobalamin (2000 la...