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

Am J Hum Genet. 1999 Jan;64(1):99-107. doi: 10.1086/302180.


In the past few years, many patients have been described who have a defect of unknown origin in the peroxisomal beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases*
  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism*
  • Cells, Cultured
  • DNA Mutational Analysis
  • Enoyl-CoA Hydratase*
  • Fatty Acids / metabolism
  • Fibroblasts / enzymology
  • Fluorescent Antibody Technique
  • Humans
  • Hydro-Lyases / deficiency
  • Hydro-Lyases / genetics*
  • Isomerism
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics*
  • Oxidation-Reduction
  • Peroxisomal Multifunctional Protein-2


  • Fatty Acids
  • Multienzyme Complexes
  • pristanic acid
  • 17-Hydroxysteroid Dehydrogenases
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Hydro-Lyases
  • Peroxisomal Multifunctional Protein-2
  • HSD17B4 protein, human
  • Enoyl-CoA Hydratase