In the past few years, many patients have been described who have a defect of unknown origin in the peroxisomal β-oxidation pathway. Complementation analysis has been done by various groups to establish the extent of the genetic heterogeneity among the patients. These studies were based on the use 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 deficiency. In a collaborative effort, we have now found that the true 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 been 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 basis of complementation analysis and found clear-cut mutations in the D-BP cDNA from all patients.
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