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
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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17-Hydroxysteroid Dehydrogenases*
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3-Hydroxyacyl CoA Dehydrogenases / chemistry
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3-Hydroxyacyl CoA Dehydrogenases / deficiency
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3-Hydroxyacyl CoA Dehydrogenases / metabolism
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ATP Binding Cassette Transporter, Subfamily D, Member 1
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ATP-Binding Cassette Transporters / metabolism
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Acetyl-CoA C-Acetyltransferase / deficiency
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Acetyl-CoA C-Acetyltransferase / metabolism
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Enoyl-CoA Hydratase*
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Humans
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Hydro-Lyases / chemistry
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Hydro-Lyases / deficiency
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Hydro-Lyases / metabolism
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Lipid Metabolism
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Multienzyme Complexes / chemistry
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Multienzyme Complexes / deficiency
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Multienzyme Complexes / metabolism
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Oxidation-Reduction
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Oxidoreductases / deficiency
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Oxidoreductases / metabolism
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Peroxisomal Disorders / enzymology
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Peroxisomal Disorders / genetics
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Peroxisomal Disorders / metabolism*
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Peroxisomal Multifunctional Protein-2
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Peroxisomes / enzymology
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Peroxisomes / metabolism*
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Peroxisomes / pathology
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Phenotype
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Racemases and Epimerases / deficiency
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Racemases and Epimerases / metabolism
Substances
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ABCD1 protein, human
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ATP Binding Cassette Transporter, Subfamily D, Member 1
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ATP-Binding Cassette Transporters
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Multienzyme Complexes
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Oxidoreductases
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17-Hydroxysteroid Dehydrogenases
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3-Hydroxyacyl CoA Dehydrogenases
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palmitoyl CoA oxidase
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Acetyl-CoA C-Acetyltransferase
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Hydro-Lyases
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Peroxisomal Multifunctional Protein-2
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HSD17B4 protein, human
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Enoyl-CoA Hydratase
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Racemases and Epimerases
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alpha-methylacyl-CoA racemase