title: Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies.
abstract: The clinical distinction between patients with a disorder of peroxisome assembly (e.g., Zellweger syndrome) and those with a defect in a peroxisomal fatty acid beta-oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complementation analysis, 24 were found to be deficient in enoylcoenzyme A hydratase/3-hydroxyacylcoenzyme A dehydrogenase bifunctional enzyme and 5 were deficient in acyl-CoA oxidase. Elevated plasma very long-chain fatty acids (VLCFA), impaired fibroblast VLCFA beta-oxidation, decreased fibroblast phytanic acid oxidation, normal plasmalogen synthesis, normal plasma L-pipecolic acid level, and normal subcellular catalase distribution were characteristic findings in both disorders. The elevation in plasma VLCFA levels and impairment in fibroblast VLCFA beta-oxidation were more severe in bifunctional-deficient than in oxidase-deficient patients. The clinical course in bifunctional deficiency (profound hypotonia, neonatal seizures, dysmorphic features, age at death approximately 9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystrophy, age at death approximately 4 yr). Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal beta-oxidation enzymes is possible.
authors.affiliation: Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Watkins
authors.forename: M C
authors.initials: MC
authors.lastname: McGuinness
authors.forename: G V
authors.initials: GV
authors.lastname: Raymond
authors.forename: B A
authors.initials: BA
authors.lastname: Hicks
authors.forename: J M
authors.initials: JM
authors.lastname: Sisk
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
mesh_terms: D042962:Acyl-CoA Oxidase; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D009097:Multienzyme Complexes / Q000172:deficiency*; D010088:Oxidoreductases / Q000172:deficiency*; D015211:Zellweger Syndrome / Q000201:enzymology*
chemical_list: D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase