Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Biochim Biophys Acta Biomembr. 2020 Dec 1;1862(12):183336. doi: 10.1016/j.bbamem.2020.183336. Epub 2020 May 8.
Disorders caused by defects in lysosomal membrane transporters form a distinct subgroup of lysosomal storage disorders (LSDs). To date, defects in only 10 lysosomal membrane transporters have been associated with inherited disorders. The clinical presentations of these diseases resemble the phenotypes of other LSDs; they are heterogeneous and often present in children with neurodegenerative manifestations. However, for pathomechanistic and therapeutic studies, lysosomal membrane transport defects should be distinguished from LSDs caused by defective hydrolytic enzymes. The involved proteins differ in function, localization, and lysosomal targeting, and the diseases themselves differ in their stored material and therapeutic approaches. We provide an overview of the small group of disorders of lysosomal membrane transporters, emphasizing discovery, pathomechanism, clinical features, diagnostic methods and therapeutic aspects. We discuss common aspects of lysosomal membrane transporter defects that can provide the basis for preclinical research into these disorders.
溶酶体膜转运蛋白缺陷引起的疾病构成了溶酶体贮积症（LSDs）的一个独特亚组。迄今为止，只有 10 种溶酶体膜转运蛋白的缺陷与遗传性疾病有关。这些疾病的临床表现与其他 LSD 的表型相似；它们具有异质性，并且常发生在具有神经退行性表现的儿童中。然而，对于发病机制和治疗研究，溶酶体膜转运缺陷应与溶酶体水解酶缺陷引起的 LSD 区分开来。所涉及的蛋白质在功能、定位和溶酶体靶向方面存在差异，并且疾病本身在贮存物质和治疗方法上也存在差异。我们概述了一小群溶酶体膜转运蛋白疾病，重点介绍了这些疾病的发现、发病机制、临床特征、诊断方法和治疗方面。我们还讨论了溶酶体膜转运蛋白缺陷的常见方面，这些方面可以为这些疾病的临床前研究提供基础。
