Tomioka Daisuke, Kato Koichi, Ozawa Tomoya, Kodama Kenji, Takahashi Hiroaki, Dochi Kenichi, Ueno Yoshiki, Nakagawa Yoshihisa
Department of Cardiology, Nagahama Red Cross Hospital, 12-7, Miyamae-cho, Nagahama-city, Shiga, 526-0053, Japan.
Department of Cardiovascular Medicine, Shiga University of Medical Science, Tsukinowa, Seta-Cho, Otsu-city, Shiga 520-2192, Japan.
Eur Heart J Case Rep. 2021 Jan 12;5(2):ytaa538. doi: 10.1093/ehjcr/ytaa538. eCollection 2021 Feb.
Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from a mutation of alpha-galactosidase A gene (), causing deficiency in alpha-galactosidase activity. The enzyme deficit can lead to storage of globotriaosylceramide in various organs including heart. Studies suggest that vasospastic angina (VSA) is associated with AFD.
This clinical case series aimed to present two female patients with AFD, including progressive cardiac involvement: a 50-year-old woman (patient number 1) and a 39-year-old woman (patient number 2) who are siblings with a male AFD patient harbouring p. Arg342Glu missense variant in alpha-galactosidase A gene (), who suffered VSA and subsequent ventricular fibrillation. Enzymatic tests and genetic analysis confirmed AFD in both female patients and histological tests revealed globotriaosylceramide deposits in their hearts. In patient number 1, a 12-lead electrocardiography and transthoracic echocardiography revealed cardiac hypertrophy. Coronary angiography revealed no organic coronary artery stenosis and vasospasms was induced by spasm provocation test. In patient number 2, no signs of cardiac hypertrophy were found, and coronary arteries had no organic stenosis with negative spasm provocation test. Both patients received enalapril therapy and enzyme replacement therapy (ERT).
Different phenotype of AFD was occurred even with the same genetic variant in female heterozygote patients. The duration of exposing accumulation of Gb3 might affect cardiac hypertrophy and vasospasms. Coronary angiography with acetylcholine provocation test should be considered in female AFD patient, especially in case with cardiac hypertrophy.
安德森-法布里病（AFD）是一种X连锁溶酶体贮积症，由α-半乳糖苷酶A基因（）突变引起，导致α-半乳糖苷酶活性缺乏。该酶缺乏可导致球三糖神经酰胺在包括心脏在内的各种器官中蓄积。研究表明，变异性心绞痛（VSA）与AFD有关。
本临床病例系列旨在介绍两名患有AFD的女性患者，包括进行性心脏受累情况：一名50岁女性（患者1号）和一名39岁女性（患者2号），她们是一名男性AFD患者的姐妹，该男性患者的α-半乳糖苷酶A基因（）存在p.Arg342Glu错义变异，曾发生VSA及随后的心室颤动。酶学检测和基因分析证实两名女性患者均患有AFD，组织学检测显示她们的心脏中有球三糖神经酰胺沉积。患者1号的12导联心电图和经胸超声心动图显示心脏肥大。冠状动脉造影显示无器质性冠状动脉狭窄，痉挛激发试验诱发了血管痉挛。患者2号未发现心脏肥大迹象，冠状动脉无器质性狭窄，痉挛激发试验结果为阴性。两名患者均接受了依那普利治疗和酶替代疗法（ERT）。
女性杂合子患者即使具有相同的基因变异，也会出现不同的AFD表型。暴露于Gb3蓄积的持续时间可能会影响心脏肥大和血管痉挛。对于女性AFD患者，尤其是伴有心脏肥大的患者，应考虑进行乙酰胆碱激发试验的冠状动脉造影。
