Kok Ken, Zwiers Kimberley C, Boot Rolf G, Overkleeft Hermen S, Aerts Johannes M F G, Artola Marta
Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Biomolecules. 2021 Feb 12;11(2):271. doi: 10.3390/biom11020271.
Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by the deficiency of α-galactosidase A (α-GalA) and the consequent accumulation of toxic metabolites such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3). Early diagnosis and appropriate timely treatment of FD patients are crucial to prevent tissue damage and organ failure which no treatment can reverse. LSDs might profit from four main therapeutic strategies, but hitherto there is no cure. Among the therapeutic possibilities are intravenous administered enzyme replacement therapy (ERT), oral pharmacological chaperone therapy (PCT) or enzyme stabilizers, substrate reduction therapy (SRT) and the more recent gene/RNA therapy. Unfortunately, FD patients can only benefit from ERT and, since 2016, PCT, both always combined with supportive adjunctive and preventive therapies to clinically manage FD-related chronic renal, cardiac and neurological complications. Gene therapy for FD is currently studied and further strategies such as substrate reduction therapy (SRT) and novel PCTs are under investigation. In this review, we discuss the molecular basis of FD, the pathophysiology and diagnostic procedures, together with the current treatments and potential therapeutic avenues that FD patients could benefit from in the future.
法布里病（FD）是一种溶酶体贮积症（LSD），其特征在于α-半乳糖苷酶A（α-GalA）缺乏，以及由此导致的毒性代谢产物如Globotriaosylceramide（Gb3）和Globotriaosylsphingosine（lysoGb3）的积累。对FD患者进行早期诊断和及时适当治疗对于预防无法通过治疗逆转的组织损伤和器官衰竭至关重要。溶酶体贮积症可能从四种主要治疗策略中获益，但迄今为止尚无治愈方法。治疗方法包括静脉注射酶替代疗法（ERT）、口服药理伴侣疗法（PCT）或酶稳定剂、底物减少疗法（SRT）以及最新的基因/RNA疗法。不幸的是，FD患者只能从ERT中获益，自2016年以来，还能从PCT中获益，这两种疗法始终与支持性辅助和预防性疗法相结合，以临床管理与FD相关的慢性肾脏、心脏和神经并发症。目前正在研究针对FD的基因疗法，底物减少疗法（SRT）和新型PCT等其他策略也在研究中。在本综述中，我们讨论了FD的分子基础、病理生理学和诊断程序，以及FD患者目前的治疗方法和未来可能受益的潜在治疗途径。
