Linhart Aleš, Paleček Tomáš
2nd Department of Internal Cardiovascular Medicine, General University Hospital, Prague, Czech Republic.
First Faculty of Medicine, Charles University, U Nemocnice 2, 128 08 Praha 2, Czech Republic.
Cardiovasc Diagn Ther. 2021 Apr;11(2):650-660. doi: 10.21037/cdt-20-593.
Fabry disease (FD) is an X-linked lysosomal storage disorder due to reduced or undetectable α-galactosidase A (AGAL-A) enzyme activity caused by pathogenic variants in the AGAL-A gene (). Tissue and organ changes are caused by widespread progressive accumulation of globotriaosylceramide (Gb) and globotriaosylsphingosine (lysoGb). The classical form of FD is multisystemic with cutaneous (angiokeratomas), neurological (peripheral neuropathy, premature stroke), renal (proteinuria and renal insufficiency), and cardiac involvement. Later onset variants may be limited to the heart. The objective of this review is to summarize the current knowledge on cardiac manifestations of FD and effects of targeted therapy. Cardiac involvement is characterized by progressive hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death (SCD). Targeted therapy is based on enzyme replacement therapy (ERT). Recently, small molecular chaperone, migalastat, became available for patients carrying amenable pathogenic GLA variants. The management of cardiac complications requires a complex approach. Several measures differ from standard clinical guidelines. Betablockers should be used with caution due to bradycardia risk, amiodarone avoided if possible, and anticoagulation used from the first appearance of atrial fibrillation. In Fabry cardiomyopathy SCD calculators are inappropriate. The awareness of FD manifestations is essential for early identification of patients and timely treatment initiation.
法布里病（FD）是一种X连锁溶酶体贮积症，由于α-半乳糖苷酶A（AGAL-A）基因的致病变异导致该酶活性降低或无法检测到。组织和器官的变化是由球三糖基神经酰胺（Gb）和球三糖基鞘氨醇（lysoGb）广泛的进行性蓄积引起的。FD的经典形式累及多系统，包括皮肤（血管角质瘤）、神经（周围神经病变、过早中风）、肾脏（蛋白尿和肾功能不全）以及心脏。晚发型变异型可能仅累及心脏。本综述的目的是总结目前关于FD心脏表现及靶向治疗效果的知识。心脏受累的特征为进行性心肌肥厚、纤维化、心律失常、心力衰竭和心源性猝死（SCD）。靶向治疗基于酶替代疗法（ERT）。最近，小分子伴侣药物米加司他已可用于携带合适的致病性GLA变异的患者。心脏并发症的管理需要综合方法。一些措施不同于标准临床指南。由于存在心动过缓风险，应谨慎使用β受体阻滞剂，尽可能避免使用胺碘酮，房颤首次出现时即应开始抗凝治疗。在法布里心肌病中，SCD计算器并不适用。了解FD的表现对于早期识别患者和及时开始治疗至关重要。
