Palakuzhiyil Shruti V, Christopher Rita, Chandra Sadanandavalli Retnaswami
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru 560029, India.
Department of Neurology, Sri Ramakrishna Ashram Charitable Hospital, Trivandrum 695010, India.
World J Biol Chem. 2020 Nov 27;11(3):99-111. doi: 10.4331/wjbc.v11.i3.99.
X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisomal β-oxidation, is caused by defects in the ATP Binding Cassette Subfamily D Member 1 () gene. X-ALD patients may be asymptomatic or present with several clinical phenotypes varying from severe to mild, severe cerebral adrenoleuko-dystrophy to mild adrenomyeloneuropathy (AMN). Although most female heterozygotes present with AMN-like symptoms after 60 years of age, occasional cases of females with the cerebral form have been reported. Phenotypic variability has been described within the same kindreds and even among monozygotic twins. There is no association between the nature of 1 mutation and the clinical phenotypes, and the molecular basis of phenotypic variability in X-ALD is yet to be resolved. Various genetic, epigenetic, and environmental influences are speculated to modify the disease onset and severity. In this review, we summarize the observations made in various studies investigating the potential modifying factors regulating the clinical manifestation of X-ALD, which could help understand the pathogenesis of the disease and develop suitable therapeutic strategies.
X连锁肾上腺脑白质营养不良（X-ALD）是一种过氧化物酶体β氧化的先天性代谢缺陷病，由ATP结合盒亚家族D成员1（ABCD1）基因缺陷引起。X-ALD患者可能无症状，或表现出从严重到轻度不等的多种临床表型，从严重的脑型肾上腺脑白质营养不良到轻度的肾上腺脊髓神经病（AMN）。虽然大多数女性杂合子在60岁后会出现类似AMN的症状，但也有女性患脑型X-ALD的个别病例报道。在同一家族甚至同卵双胞胎中都观察到了表型变异性。ABCD1突变的性质与临床表型之间没有关联，X-ALD表型变异性的分子基础尚待解决。推测各种遗传、表观遗传和环境因素会影响疾病的发病和严重程度。在这篇综述中，我们总结了各项研究中关于调节X-ALD临床表现的潜在影响因素的观察结果，这有助于理解该疾病的发病机制并制定合适的治疗策略。
