Clinical consequences of defects in peroxisomal beta-oxidation

Biochem Soc Trans. 2001 May;29(Pt 2):298-305. doi: 10.1042/0300-5127:0290298.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases*
  • 3-Hydroxyacyl CoA Dehydrogenases / chemistry
  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / metabolism
  • Acetyl-CoA C-Acetyltransferase / deficiency
  • Acetyl-CoA C-Acetyltransferase / metabolism
  • Enoyl-CoA Hydratase*
  • Humans
  • Hydro-Lyases / chemistry
  • Hydro-Lyases / deficiency
  • Hydro-Lyases / metabolism
  • Lipid Metabolism
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / metabolism
  • Oxidation-Reduction
  • Oxidoreductases / deficiency
  • Oxidoreductases / metabolism
  • Peroxisomal Disorders / enzymology
  • Peroxisomal Disorders / genetics
  • Peroxisomal Disorders / metabolism*
  • Peroxisomal Multifunctional Protein-2
  • Peroxisomes / enzymology
  • Peroxisomes / metabolism*
  • Peroxisomes / pathology
  • Phenotype
  • Racemases and Epimerases / deficiency
  • Racemases and Epimerases / metabolism

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Multienzyme Complexes
  • Oxidoreductases
  • 17-Hydroxysteroid Dehydrogenases
  • 3-Hydroxyacyl CoA Dehydrogenases
  • palmitoyl CoA oxidase
  • Acetyl-CoA C-Acetyltransferase
  • Hydro-Lyases
  • Peroxisomal Multifunctional Protein-2
  • HSD17B4 protein, human
  • Enoyl-CoA Hydratase
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase