Molecular basis of mitochondrial fatty acid oxidation defects.

A dozen separate inherited disorders of mitochondrial fatty acid beta-oxidation have been described in humans. This represents about half of the potential sites for genetic error that can affect this important pathway of energy metabolism. As the characterization of these disorders at the clinical and biochemical levels has progressed rapidly, so has the delineation of the molecular defects that underlie them. The most commonly recognized disorder of beta-oxidation is medium-chain acyl-CoA dehydrogenase deficiency; a striking feature of this disorder is that there is a single point mutation that accounts for 90% of the variant alleles among patients with medium-chain acyl-CoA dehydrogenase deficiency. Molecular defects of other enzymes in the pathway have been identified, and it seems likely that a complete description of these defects at the molecular level is a realistic goal. In basic biological terms, such studies will lead to a better understanding of the genetic control exerted on this pathway. In clinical terms, they will lead to improved understanding of the molecular pathophysiology of these diseases and may well provide the necessary techniques to proceed with the screening of these disorders.