Characteristic cardiac capillary pericytes in a Fabry disease patient receiving enzyme replacement therapy

Abstract

Fabry disease, a lysosomal disorder caused by deficiency in α-galactosidase A, patients report chest pain in the absence of epicardial coronary artery stenosis. Although it is conceivable that coronary microvascular dysfunction due to globotriaosylceramide (GL-3) accumulation within the vasculature causes angina, the precise histology was unknown. A 34-year-old male patient diagnosed with Fabry disease [NM_000169.3:c.1089_1090insTCGC (p.Tyr365Lysfs*11)] and treated for 6 years with enzyme replacement therapy (ERT) was referred to our cardiology department because of palpitations and precordial discomfort. He was diagnosed for paroxysmal atrial fibrillation and subsequently underwent catheter ablation therapy. The procedure resolved his palpitations, but his precordial discomfort remained. Again, coronary angiography showed no organic stenosis. A 24-hour Holter electrocardiogram detected neither arrhythmia nor ischemic changes. Echocardiography showed normal wall motion with diffuse left ventricular hypertrophy. Endomyocardial biopsy revealed severe vacuolated hypertrophied myocytes appearing transparent, like a lace curtain, which is characteristic of Fabry disease (Figure A, A’ and B). Electron microscopic examination revealed abundant lamellar bodies with a myelin-like configuration within cardiomyocytes and interstitial macrophages, indicating GL-3 deposition (Figure C, D and E). We also detected numerous interstitial microcapillaries showing abundant lamellar body deposits within the capillary pericytes but not the endothelial cells (Figure F, F’-1 and F’-2. Pericytes surrounding the endothelial cells can regulate capillary blood flow in microvascular beds. Our pathological findings suggest progressive lamellar body accumulation caused angina by disrupting microvascular circulation. This case highlights progression of microvascular Fabry disease especially in capillary pericytes and also a need for develop therapies targeting capillary circulation.