COMPLEMENTATION ANALYSIS OF FIBROBLASTS FROM PEROXISOMAL FATTY-ACID OXIDATION DEFICIENT PATIENTS SHOWS HIGH-FREQUENCY OF BIFUNCTIONAL ENZYME DEFICIENCY PLUS INTRAGENIC COMPLEMENTATION - UNEQUIVOCAL EVIDENCE FOR DIFFERENTIAL DEFECTS IN THE SAME ENZYME PROTEIN

In the last few years many patients have been reported with a defect i n peroxisomal fatty acid beta-oxidation of unknown origin. Using a com bined approach based on direct activity measurements of straight-chain acyl-CoA oxidase and complementation analysis after somatic cell fusi on of fibroblasts, we have now classified 13 patients into 4 distinct groups representing different gene defects. Remarkably, we found intra genic complementation in group 2 so that group 2 is in fact made up of 3 distinct subgroups. The underlying basis for this peculiar phenomen on probably has to do with the fact that bifunctional protein harbors two catalytic activities including enoyl-CoA hydratase and 3-hydroxyac yl-CoA dehydrogenase. In group 2A enoyl-CoA hydratase and 3-hydroxyacy l-CoA dehydrogenase are defective whereas in group 2B and 2C either th e hydratase or 3-hydroxyacyl-CoA dehydrogenase component of the bifunc tional protein is deficient. (C) 1997 Academic Press.