Pathological capillary analysis of ischemia with non-obstructive coronary arteries in a Fabry disease patient receiving enzyme replacement therapy.

Fabry disease is a lysosomal disorder caused by an α-galactosidase A deficiency, which often causes angina in the absence of epicardial coronary artery stenosis. It is conceivable that epicardial and microvascular coronary dysfunction due to globotriaosylceramide and related glycoshingolipid accumulation within the vasculature causes ischemia with non-obstructive coronary arteries (INOCA). However, the precise histology remained unknown. We present the case of a 44-year-old male diagnosed with Fabry disease and treated with enzyme replacement therapy (ERT), who was referred to our cardiology department after complaining of exertional and rest precordial discomfort. Electrocardiography showed left ventricular hypertrophy (LVH) with strained ST segment depression. Echocardiography showed normal wall motion with diffuse LVH. Although coronary angiography showed no organic stenosis, spasms were provoked by intracoronary ergonovine injection. Invasive assessment of the microvasculature physiology showed the mean index of microcirculatory resistance to be 42 and the mean coronary flow reserve to be 1.6, which is indicative of coronary microvascular dysfunction. Endomyocardial biopsy revealed abundant accumulation of lamellar bodies within both cardiomyocytes and capillary pericytes, but not endothelial cells, suggesting microvascular flow disruption attributable to pericyte contraction and capillary constriction. This case highlights INOCA associated with a microvascular lesion related to Fabry disease in a patient receiving ERT as well as the need to develop therapies targeting the capillary circulation.