Adrenoleukodystrophy (ALD) is a rare X-linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell- and tissue-specific role of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials, and the advent of newborn screening in the United States. In ALD, very long chain fatty acid (VLCFA) chain-length-dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety-specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.

中文翻译：

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X连锁肾上腺脑白质营养不良：病理学、病理生理学、诊断测试、新生儿筛查和治疗


肾上腺脑白质营养不良 (ALD) 是一种罕见的 X 连锁疾病，由过氧化物酶体 ABCD1 基因突变引起。这篇综述总结了我们目前对实验治疗策略背景下脂质种类的致病细胞和组织特异性作用的理解，并概述了美国的重要历史发展、治疗试验和新生儿筛查的出现。在 ALD 中，内质网应激和线粒体自由基生成系统的极长链脂肪酸 (VLCFA) 链长度依赖性失调已被证明可诱导细胞死亡途径，这为治疗部分特异性 VLCFA 减少和抗氧化策略提供了理论基础。新生儿筛查项目的持续增加以及正在进行和最近的治疗研究的可喜结果为 ALD 带来了希望。