Malonyl-CoA decarboxylase deficiency is a rare inborn error of metabolism. It has been suggested but never demonstrated that many of the clinical features arise due to inhibition of mitochondrial fatty acid oxidation by accumulated malonyl-CoA. We studied the oxidation of fatty acids in cultured skin fibroblasts from a recently described patient with malonyl-CoA decarboxylase deficiency. There was a marked reduction in the oxidation of palmitic and myristic acids both under baseline conditions and when the cells were cultured in the presence of high concentrations of acetate, a malonyl-CoA precursor. These results suggest that there is inhibition of fatty acid oxidation in malonyl-CoA decarboxylase deficiency and that this inhibition may be related to some of the clinical phenotypes.
