Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect 1 in 5,000 live births. LSDs typically present in infancy and childhood, although adult-onset forms also occur. Most LSDs have a progressive neurodegenerative clinical course, although symptoms in other organ systems are frequent. LSD-associated genes encode different lysosomal proteins, including lysosomal enzymes and lysosomal membrane proteins. The lysosome is the key cellular hub for macromolecule catabolism, recycling and signalling, and defects that impair any of these functions cause the accumulation of undigested or partially digested macromolecules in lysosomes (that is, 'storage') or impair the transport of molecules, which can result in cellular damage. Consequently, the cellular pathogenesis of these diseases is complex and is currently incompletely understood. Several LSDs can be treated with approved, disease-specific therapies that are mostly based on enzyme replacement. However, small-molecule therapies, including substrate reduction and chaperone therapies, have also been developed and are approved for some LSDs, whereas gene therapy and genome editing are at advanced preclinical stages and, for a few disorders, have already progressed to the clinic.

中文翻译：

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溶酶体贮积病。

溶酶体贮积病（LSD）是一组以溶酶体功能障碍为特征的70多种疾病，其中大多数是常染色体隐性遗传。这些疾病个别罕见，但总共影响5,000例活产中的1例。LSDs通常存在于婴儿期和儿童期，尽管也有成人发作的形式。尽管其他器官系统中的症状很常见，但大多数LSD都有进行性神经退行性疾病的临床过程。与LSD相关的基因编码不同的溶酶体蛋白，包括溶酶体酶和溶酶体膜蛋白。溶酶体是大分子分解代谢，循环利用和信号传导的关键细胞中心，损害任何这些功能的缺陷都会导致未消化或部分消化的大分子在溶酶体中积累（即“存储”））或损害分子的运输，这可能会导致细胞损伤。因此，这些疾病的细胞发病机理是复杂的，目前尚不完全清楚。几种LSD可以采用经批准的，特定于疾病的疗法进行治疗，这些疗法主要基于酶的替代。然而，包括底物减少和分子伴侣治疗在内的小分子疗法也已被开发出来，并被批准用于某些LSDs，而基因疗法和基因组编辑则处于临床前阶段，对于一些疾病，已经进入临床。主要基于酶替代的疾病特异性疗法。然而，包括底物减少和分子伴侣治疗在内的小分子疗法也已被开发出来，并被批准用于某些LSDs，而基因疗法和基因组编辑则处于临床前阶段，对于一些疾病，已经进入临床。主要基于酶替代的疾病特异性疗法。然而，包括底物减少和分子伴侣治疗在内的小分子疗法也已被开发出来，并被批准用于某些LSDs，而基因疗法和基因组编辑则处于临床前阶段，对于一些疾病，已经进入临床。