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Methylmalonic Semialdehyde Dehydrogenase Deficiency: Psychomotor Delay and Methylmalonic Aciduria without Metabolic Decompensation

https://doi.org/10.1006/mgme.1998.2737Get rights and content

Abstract

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 methylmalonyl-CoA 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 labeledS- andR-3-HIBA andS- andR-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 ofS-3-AIBA—nearly 10 times that observed in mutase deficiency. The ratio ofR-AIBA toS-AIBA of <1 also reflects this disorder.

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