Peroxisomal bifunctional protein deficiency revisited: Resolution of its true enzymatic and molecular basis

In the past few years, many patients have been described who have a defect of unknown origin in the peroxisomal beta-oxidation pathway. Complementatio n analysis has been done by various groups to establish the extent of the g enetic heterogeneity among the patients. These studies were based on the us e of two established cell lines, one with a deficiency of acyl-CoA oxidase and one with a deficiency of L-bifunctional protein (L-BP), and they showed that most patients belong to the L-BP-deficient group. However, molecular analysis of the cDNA encoding L-BP in patients failed to show any mutations . The recent identification of a new D-specific bifunctional protein (D-BP) prompted us to reinvestigate the original patient with presumed L-BP defic iency. In a collaborative effort, we have now found that the hue defect in this patient is at the level of the D-BP and not at the Level of the L-BP. Our results suggest that most, if not all, patients whose condition has bee n diagnosed as L-BP are, in fact, D-BP deficient. We tested this hypothesis in nine patients whose condition was diagnosed as L-BP deficiency on the b asis of complementation analysis and found clear-cut mutations in the D-BP cDNA from all patients.