Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Nature. 2014 Jun 5;510(7503):68-75. doi: 10.1038/nature13476.
Lysosomal storage diseases are inborn errors of metabolism, the hallmark of which is the accumulation, or storage, of macromolecules in the late endocytic system. They are monogenic disorders that occur at a collective frequency of 1 in 5,000 live births and are caused by inherited defects in genes that mainly encode lysosomal proteins, most commonly lysosomal enzymes. A subgroup of these diseases involves the lysosomal storage of glycosphingolipids. Through our understanding of the genetics, biochemistry and, more recently, cellular aspects of sphingolipid storage disorders, we have gained insights into fundamental aspects of cell biology that would otherwise have remained opaque. In addition, study of these disorders has led to significant progress in the development of therapies, several of which are now in routine clinical use. Emerging mechanistic links with more common diseases suggest we need to rethink our current concept of disease boundaries.
溶酶体贮积症是先天性代谢缺陷，其特征是大分子在晚期内吞系统中积累或储存。它们是单基因疾病，在活产儿中的发生率为 1/5000，由编码溶酶体蛋白（主要是溶酶体酶）的基因遗传缺陷引起。这些疾病的一个亚组涉及糖脂的溶酶体储存。通过了解鞘脂贮积症的遗传学、生物化学，以及最近的细胞方面，我们深入了解了细胞生物学的基本方面，否则这些方面仍将难以理解。此外，对这些疾病的研究导致治疗方法的显著进展，其中几种已常规用于临床。与更常见疾病的新兴机制联系表明，我们需要重新思考当前的疾病边界概念。
