title: Clinical consequences of defects in peroxisomal beta-oxidation.
abstract: The disorders of peroxisomal beta-oxidation, which have been well characterised at the molecular level, include defects of acyl-CoA oxidase, defects of the D-bifunctional protein (D-BP) (including specific defects of its enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase components), defects of the very-long-chain fatty acid (VLCFA)-CoA importer [X-linked adrenoleukodystrophy (ALD)] and alpha-methylacyl-CoA racemase deficiency. A survey of the clinical consequences of these defects indicates that defects in the acyl-CoA oxidase and D-BP can produce neonatal hypotonia, seizures in early infancy, retinopathy and progressive neurological dysfunction with leukodystrophy on imaging. Defects in the VLCFA-CoA importer and in the racemase do not produce disease until a long time after the neonatal period. However, again the clinical picture is dominated by neurological disease: impaired cognitive function with leukodystrophy in childhood X-linked ALD and retinopathy and neuropathy in racemase deficiency. It is difficult to escape the conclusion that defective peroxisomal beta-oxidation has effects (such as impaired neuronal migration in the developing brain), which are more serious than those produced by the accumulation of substrates (VLCFAs, pristanic acid) alone.
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, U.K. p.clayton@ich.ucl.ac.uk
authors.forename: P T
authors.initials: PT
authors.lastname: Clayton
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000172:deficiency / Q000378:metabolism; D004746:Enoyl-CoA Hydratase; D006801:Humans; D006836:Hydro-Lyases / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D050356:Lipid Metabolism; D009097:Multienzyme Complexes / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000172:deficiency / Q000378:metabolism; D018901:Peroxisomal Disorders / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D019998:Racemases and Epimerases / Q000172:deficiency / Q000378:metabolism
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C028427:palmitoyl CoA oxidase; D000101:Acetyl-CoA C-Acetyltransferase; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase