Defective ABCD1 causes ALD

The 70-kDa peroxisomal membrane protein (PMP70) and the adrenoleukodystrophy protein (ALDP aka ABCD1) are half ATP binding cassette (ABC) transporters in the peroxisome membrane. They are involved in metabolic transport of long and very long chain fatty acids into peroxisomes. Mutations in the ALD gene result in the X-linked neurodegenerative disorder adrenoleukodystrophy (ALD; MIM:300100). ABCD1 deficiency impairs the peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA) and facilitates their further chain elongation by ELOVL1 resulting in accumulation of VLCFA in plasma and tissues. While all patients with ALD have mutations in the ABCD1 gene, there is no general genotype-phenotype correlation. In addition to ABCD1, other genes and environmental factors determine clinical features of ALD (Kemp et al. 2012, Berger et al. 2014).

70kDa的过氧化物酶体膜蛋白（PMP70）和肾上腺脑白质营养不良蛋白（ALDP，又称ABCD1）是过氧化物酶体膜中的半ATP结合盒（ABC）转运蛋白。它们参与长链和超长链脂肪酸的代谢转运进入过氧化物酶体。ALD基因的突变导致X连锁神经退行性疾病肾上腺脑白质营养不良（ALD；MIM：300100）。ABCD1的缺乏损害了过氧化物酶体中非常长链脂肪酸（VLCFA）的β-氧化，并促进由ELOVL1引起的VLCFA链的进一步延长，导致血浆和组织中VLCFA的积累。尽管所有ALD患者都存在ABCD1基因的突变，但并未发现普遍的基因型-表型相关性。除了ABCD1之外，其他基因和环境因素也决定了ALD的临床特征（Kemp等，2012年，Berger等，2014年）。