Yogasundaram Haran, Kim Daniel, Oudit Omar, Thompson Richard B, Weidemann Frank, Oudit Gavin Y
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Chemistry and Biochemistry, City College, City University of New York, New York, NY.
Can J Cardiol. 2017 Jul;33(7):883-897. doi: 10.1016/j.cjca.2017.04.015. Epub 2017 May 4.
Anderson-Fabry disease (AFD) is an X-linked recessive, multisystem disease of lysosomal storage. A mutation in the gene encoding the hydrolase enzyme α-galactosidase A results in its deficiency, or complete absence of activity. Subsequent progressive intracellular accumulation of glycosphingolipids, predominantly globotriaosylceramide, in various tissues, results in progressive organ dysfunction and failure, most commonly affecting the kidneys, nervous system, skin, eyes, vascular endothelium, and the heart. Cardiac involvement in AFD represents a leading cause of morbidity and mortality. Globotriaosylceramide accumulation affects cardiomyocytes, smooth muscle cells, vascular endothelial cells, and fibroblasts leading to various pathologies including valvular regurgitation, conduction disease and arrhythmias, coronary microvascular dysfunction, and right and left ventricular hypertrophy (LVH) leading to early diastolic dysfunction and late-stage systolic impairment. Diagnosis is on the basis of decreased plasma α-galactosidase activity in men and positive genetic testing in women. Contemporary large-scale screening studies have revealed a prevalence of 1%-5% in patients with unexplained LVH in multiple cohorts. Cardiac magnetic resonance imaging, with its unique tissue characterization capabilities, is the most important imaging modality to assess for cardiomyopathy in patients with AFD. Enzyme replacement therapy is indicated in AFD patients with significant organ involvement, and has been shown to clear sphingolipids from endothelial cells in other organs, as well as to reduce left ventricular mass as early as 6 months after starting treatment. There is increasing evidence that enzyme replacement therapy might be more effective if given at earlier stages of disease, before the development of LVH and myocardial fibrosis.
安德森-法布里病（AFD）是一种X连锁隐性溶酶体贮积症，多系统受累。编码水解酶α-半乳糖苷酶A的基因突变导致该酶缺乏或完全丧失活性。随后，糖鞘脂（主要是球三糖神经酰胺）在各种组织中进行性细胞内蓄积，导致进行性器官功能障碍和衰竭，最常累及肾脏、神经系统、皮肤、眼睛、血管内皮和心脏。AFD的心脏受累是发病和死亡的主要原因。球三糖神经酰胺蓄积影响心肌细胞、平滑肌细胞、血管内皮细胞和成纤维细胞，导致各种病理改变，包括瓣膜反流、传导疾病和心律失常、冠状动脉微血管功能障碍以及左右心室肥厚（LVH），进而导致早期舒张功能障碍和晚期收缩功能损害。诊断依据男性血浆α-半乳糖苷酶活性降低以及女性基因检测阳性。当代大规模筛查研究显示，在多个队列中，不明原因LVH患者的患病率为1%-5%。心脏磁共振成像凭借其独特的组织特征识别能力，是评估AFD患者心肌病的最重要影像学检查方法。酶替代疗法适用于有明显器官受累的AFD患者，已证明该疗法可清除其他器官内皮细胞中的鞘脂，并且在开始治疗后6个月即可减轻左心室质量。越来越多的证据表明，如果在疾病早期、LVH和心肌纤维化出现之前给予酶替代疗法，可能会更有效。
