Second Department of Internal Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Division of Medical Genetics, University of Versailles and AP-HP Paris-Saclay, Paris, France.
Eur J Heart Fail. 2020 Jul;22(7):1076-1096. doi: 10.1002/ejhf.1960. Epub 2020 Aug 14.
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene that leads to reduced or undetectable α-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.
法布雷病(FD)是一种 X 连锁溶酶体贮积症,由α-半乳糖苷酶 A(GLA)基因的致病性变异引起,导致α-半乳糖苷酶 A 酶活性降低或检测不到,全身性细胞内糖鞘脂和其去酰基形式神经酰胺三己糖苷(Gb3)蓄积。FD 可累及多个系统,包括神经、肾脏、皮肤和心脏,也可仅限于心脏。心脏受累表现为进行性心肌肥厚、纤维化、心律失常、心力衰竭和心脏性猝死。FD 的心脏管理需要特定的措施,包括在携带可治疗的致病性 GLA 基因突变的患者中进行酶替代治疗或小分子药物伴侣,以及更一般的心脏症状和并发症的管理。本文总结了 FD 相关心脏病的现有知识和管理的专家共识建议。