Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Int J Mol Sci. 2020 Apr 14;21(8):2704. doi: 10.3390/ijms21082704.
Lysosomal storage disorders (LSDs) are characterized by an accumulation of various substances, such as sphingolipids, mucopolysaccharides, and oligosaccharides. The LSD enzymes responsible for the catabolism are active at acidic pH in the lysosomal compartment. In addition to the classically established lysosomal degradation biochemistry, recent data have suggested that lysosome plays a key role in the autophagy where the fusion of autophagosome and lysosome facilitates the degradation of amino acids. A failure in the lysosomal function leads to a variety of manifestations, including neurovisceral disorders. While affected individuals appear to be normal at birth, they gradually become symptomatic in childhood. Biomarkers for each condition have been well-documented and their proper selection helps to perform accurate clinical diagnoses. Based on the natural history of disorders, it is now evident that the existing treatment becomes most effective when initiated during presymptomatic period. Neonatal screening provides such a platform for inborn error of metabolism in general and is now expanding to LSDs as well. These are implemented in some areas and countries, including Taiwan and the U.S. In this short review, we will discuss several issues on some selected biomarkers for LSDs involving Fabry, Niemann-Pick disease type C, mucopolysaccharidosis, and oligosaccharidosis, with a focus on mass spectrometry application to biomarker discovery and detection.
溶酶体贮积症（LSD）的特征是各种物质（如鞘脂、黏多糖和寡糖）的积累。负责分解代谢的 LSD 酶在溶酶体隔室中在酸性 pH 下具有活性。除了经典的溶酶体降解生物化学之外，最近的数据表明溶酶体在自噬中起着关键作用，其中自噬体和溶酶体的融合有助于氨基酸的降解。溶酶体功能的失败会导致多种表现，包括神经内脏疾病。虽然受影响的个体在出生时似乎正常，但他们会在儿童期逐渐出现症状。每种病症的生物标志物都有详细的记录，适当的选择有助于进行准确的临床诊断。根据疾病的自然史，现在显然是在出现症状前开始治疗时，现有的治疗方法最有效。新生儿筛查为一般代谢性遗传病提供了这样一个平台，现在也在扩展到 LSD。包括台湾和美国在内的一些地区和国家已经实施了这些筛查。在这篇简短的综述中，我们将讨论几种 LSD 的选定生物标志物的问题，涉及法布里病、尼曼-皮克病 C 型、黏多糖贮积症和寡糖贮积症，重点是质谱法在生物标志物发现和检测中的应用。
