Impaired mitochondrial fatty acid oxidative flux in fibroblasts from a patient with malonyl-CoA decarboxylase deficiency

Malonyl-CoA decarboxylase deficiency is a rare inborn error of metabolism. It has been suggested but never demonstrated that many of the clinical feat ures arise due to inhibition of mitochondrial fatty acid oxidation by accum ulated malonyl-CoA. We studied the oxidation of fatty acids in cultured ski n fibroblasts from a recently described patient with malonyl-CoA decarboxyl ase deficiency. There was a marked reduction in the oxidation of palmitic a nd myristic acids both under baseline conditions and when the cells were cu ltured in the presence of high concentrations of acetate, a malonyl-CoA pre cursor. These results suggest that there is inhibition of fatty acid oxidat ion in malonyl-CoA decarboxylase deficiency and that this inhibition may be related to some of the clinical phenotypes. (C) 2001 Academic Press.