A patient presenting with developmental delay but no episodes of metabolic acidosis was found to excrete significant amounts of methylmalonate (MMA) without any associated increased excretion of malonate, ethylmalonate, 3-hydroxypropionate, or β-alanine. In contrast to patients with methylmalonic aciduria due to deficient mutase or impaired cobalamin metabolism, there was no increase of propionylcarnitine in blood or urine. The activity of methylmalonylCoA mutase and the pathway for cobalamin metabolism were also intact. The quantitative levels of the various labeled enantiomers of 3-hydroxyisobutyric (3-HIBA), 3-aminoisobutyric (3-AIBA), MMA, and propionylcarnitine were compared following separate intravenous infusions of equimolar doses of [2H8]valine or [2H4]thymine in this patient and another with methylmalonyl-CoA mutase deficiency. Levels of labeled S- and R- 3-HIBA and S- and R-3-AIBA indicated an isolated defect in methylmalonic semialdehyde dehydrogenase in this patient. This condition can be recognized by plasma MMA levels of ~8.5 μM (cf. 400 μM in mutase deficiency), urine MMA of 20-55 μmol/kg/24 h (cf. 1150 μmol/kg/24 h), no increase in propionylcarnitine following an oral carnitine load, and increased excretion of S-3-AIBA-nearly 10 times that observed in mutase deficiency. The ratio of RAIBA to S-AIBA of < 1 also reflects this disorder.
- 3- aminoisobutyric
- Methylmalonic acid
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism