Pierre-Louis Bredy, Kumar Anil, Frishman William H
Department of Medicine, Division of Cardiology, New York Medical College/Westchester Medical Center, Valhalla, NY 10595, USA.
Cardiol Rev. 2009 Jan-Feb;17(1):31-5. doi: 10.1097/CRD.0b013e31818adc50.
Fabry disease is a rare inherited lysosomal storage disorder caused by the partial or complete deficiency of the lysosomal enzyme alpha galactosidase A (alpha-Gal A), resulting in excess cellular glycosphingolipid deposition. Accumulation of the neutral glycosphingolipid globotriaosyl-ceramide predominates and involves small blood vessels, nerves, dorsal root ganglia, renal glomerular, and tubular epithelial cells and cardiomyocytes. Disease transmission is X-linked, therefore it predominantly affects males and females as asymptomatic carriers. However, females may also develop symptomatic disease of varying severity. Glycosphingolipid deposition in various tissues leads to episodic pain crises and acroparesthesias, gastrointestinal disturbances, angiokeratomas, corneal, and lenticular opacities, and eventually in the third to fifth decades of life, the kidney, heart and central nervous system are involved. Cardiac involvement is usually part of the multisystem disorder and presents in the fourth decade with other organ manifestations; however, a variant of Fabry disease with predominant cardiac manifestations has also been recognized. Patients may present with angina pectoris, dyspnea, palpitations, or syncope, and these symptoms are due to vascular, endothelial, myocardial (with increase in left ventricular mass), and conduction system involvement. Advanced cardiac disease may require a permanent pacemaker and cardiac transplant. Substrate inhibition with enzyme replacement therapy and gene therapy instituted early in the disease course might slow progression of the cardiac manifestations.
法布里病是一种罕见的遗传性溶酶体贮积症，由溶酶体酶α-半乳糖苷酶A（α-Gal A）部分或完全缺乏引起，导致细胞内糖鞘脂沉积过多。中性糖鞘脂Globotriaosyl-神经酰胺的积累占主导地位，累及小血管、神经、背根神经节、肾小球、肾小管上皮细胞和心肌细胞。疾病传播为X连锁，因此主要影响男性，女性为无症状携带者。然而，女性也可能出现不同严重程度的症状性疾病。各种组织中的糖鞘脂沉积会导致发作性疼痛危机和肢端感觉异常、胃肠道紊乱、血管角质瘤、角膜和晶状体混浊，最终在生命的第三个到第五个十年，肾脏、心脏和中枢神经系统会受到影响。心脏受累通常是多系统疾病的一部分，在第四个十年出现其他器官表现；然而，也已经认识到一种以心脏表现为主的法布里病变体。患者可能出现心绞痛、呼吸困难、心悸或晕厥，这些症状是由于血管、内皮、心肌（左心室质量增加）和传导系统受累所致。晚期心脏病可能需要永久起搏器和心脏移植。在疾病过程早期采用酶替代疗法和基因疗法进行底物抑制可能会减缓心脏表现的进展。
