Clinical consequences of defects in peroxisomal β-oxidation

被引:32
作者
Clayton, PT [1 ]
机构
[1] UCL, Inst Child Hlth, Biochem Endocrinol & Metab Unit, London WC1N 1EH, England
关键词
bile acids; fatty acids; neurometabolic disease; peroxisomal disorders;
D O I
10.1042/BST0290298
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha -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.
引用
收藏
页码:298 / 305
页数:8
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