Kemp Stephan, Berger Johannes, Aubourg Patrick
Department of Clinical Chemistry, University of Amsterdam, The Netherlands.
Biochim Biophys Acta. 2012 Sep;1822(9):1465-74. doi: 10.1016/j.bbadis.2012.03.012. Epub 2012 Mar 28.
X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. The two main clinical phenotypes of X-ALD are adrenomyeloneuropathy (AMN) and inflammatory cerebral ALD that manifests either in children or more rarely in adults. About 65% of heterozygote females develop symptoms by the age of 60years. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane protein. ALDP 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 have mutations in the ABCD1 gene, there is no general genotype-phenotype correlation. Environmental factors and a multitude of modifying genes appear to determine the clinical manifestation in this monogenetic but multifactorial disease. This review focuses on the clinical, biochemical, genetic and pathophysiological aspects of X-ALD.
X连锁肾上腺脑白质营养不良（X-ALD）是最常见的过氧化物酶体病。X-ALD的两种主要临床表型是肾上腺脊髓神经病（AMN）和炎症性脑型ALD，后者在儿童期发病，在成人中发病更为罕见。约65%的杂合子女性在60岁时出现症状。ABCD1基因突变会影响编码蛋白ALDP（一种位于过氧化物酶体膜蛋白中的ATP结合盒转运体）的功能。ALDP缺乏会损害极长链脂肪酸（VLCFA）的过氧化物酶体β氧化，并通过ELOVL1促进其进一步链延长，导致VLCFA在血浆和组织中蓄积。虽然所有患者都有ABCD1基因突变，但不存在普遍的基因型-表型相关性。环境因素和众多修饰基因似乎决定了这种单基因但多因素疾病的临床表现。本综述重点关注X-ALD的临床、生化、遗传和病理生理方面。
