Mitochondrial methylmalonate semialdehyde dehydrogenase (ALDH6A1) catalyzes the reaction of methylmalonate semialdehyde, NAD+, and CoA to form propionyl-CoA, CO2, and NADH + H+. A human ALDH6A1 gene has been cloned. Its sequence is closely homologous to that of the better-characterized rat enzyme (Kedishvili et al. 1992) and a missense mutation in a normally well-conserved codon has been found in the allele of the gene from a patient with a defect in methylmalonic semialdehyde dehydrogenase activity (Chambliss et al. 2000).