title: Peroxisomal bifunctional enzyme deficiency.
abstract: Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.
authors.affiliation: Kennedy Institute of Handicapped Children, Baltimore, Maryland 21205.
authors.forename: P A
authors.initials: PA
authors.lastname: Watkins
authors.forename: W W
authors.initials: WW
authors.lastname: Chen
authors.forename: C J
authors.initials: CJ
authors.lastname: Harris
authors.forename: G
authors.initials: G
authors.lastname: Hoefler
authors.forename: S
authors.initials: S
authors.lastname: Hoefler
authors.forename: D C
authors.initials: DC
authors.lastname: Blake
authors.forename: A
authors.initials: A
authors.lastname: Balfe
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.forename: M E
authors.initials: ME
authors.lastname: Beard
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000326:Adrenoleukodystrophy; D001921:Brain / Q000473:pathology; D002458:Cell Fractionation; D002478:Cells, Cultured; D002793:Cholic Acids / Q000378:metabolism; D003937:Diagnosis, Differential; D004746:Enoyl-CoA Hydratase / Q000172:deficiency* / Q000235:genetics; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005347:Fibroblasts / Q000032:analysis / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency*; D015151:Immunoblotting; D007231:Infant, Newborn; D007535:Isomerases; D008099:Liver / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000201:enzymology* / Q000473:pathology; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D002793:Cholic Acids; D005227:Fatty Acids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; C003681:3,7,12-trihydroxycoprostanic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D006836:Hydro-Lyases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases