鞘脂糖病是一组关于鞘糖脂代谢的遗传性罕见疾病,分类为溶酶体贮积症(LSD)。这里,我们关注八种遗传性疾病,包括GM1神经节苷脂,GM2神经节苷脂增多症,法布里病,戈谢病,异色性脑白质营养不良,Krabbe病,尼曼-皮克病A和B,和法伯病。大多数情况下,关键酶的致病突变是功能丧失,导致底物积累和产品不足。因此,底物的细胞超负荷导致脂毒性,对细胞和器官功能有害。在鞘脂症的临床表现方面,多个系统和器官,尤其是中枢神经系统(CNS)通常受到影响。至于诊断策略,酶活性测定和基因测序是有帮助的。直到现在,有限的治疗方法已被批准用于治疗鞘脂症,有一些潜在的进一步评估策略。总的来说,酶替代疗法(ERT),底物减少疗法(SRT),分子伴侣是酶缺乏症的可行选择,但由于预防血脑屏障,这些疗法仅限于缓解CNS病变和症状。其他可能的治疗方法,如基因疗法,骨髓移植(BMT),造血干细胞移植(HSCT)需要进一步评估。
Sphingolipidoses is a cluster of genetic rare disorders regarding glycosphingolipid metabolism, classified as lysosomal storage disorders (LSD). Here, we focus on eight inheritable diseases, including GM1 gangliosidosis, GM2 gangliosidosis, Fabry disease, Gaucher\'s disease, metachromatic leukodystrophy, Krabbe disease, Niemann-Pick disease A and B, and Farber disease. Mostly, pathogenic mutations in the key enzyme are loss-function, resulting in accumulation of substrates and deficiency of products. Thus, cellular overload of substrates causes lipotoxicity, which is deleterious to cellular and organ function. In the terms of clinical manifestations in sphingolipidoses, multiple systems and organs, especially central nervous system (CNS) are usually affected. As for diagnosis strategy, enzymatic activity assay and genetic sequencing are helpful. Up till now, limited treatment approaches have approved for treating sphingolipidoses, with some potential strategies for further evaluation. In general, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and molecular chaperones are feasible choices for enzyme deficiency disorders, but these therapies are limited to relieve CNS lesions and symptoms due to prevention from blood-brain barrier. Other possible treatments such as gene therapy, bone marrow transplantation (BMT), and hematopoietic stem cell transplantation (HSCT) need further evaluation.