Management of Hypertension in Fabry Disease

Abstract

Fabry disease (FD), a rare X-linked lysosomal storage disorder that depletes alpha-galactosidase A (α-GalA), is caused by mutations in the GLA gene. Diminished α-GalA enzyme activity results in the accumulation of Gb3 and lyso-Gb3. The pathophysiology of hypertension in FD is complex and unclear. The storage of Gb3 in arterial endothelial cells and smooth muscle cells is known to produce vascular injury by increasing oxidative stress and inflammatory cytokines as a primary pathophysiological mechanism. In addition, Fabry nephropathy developed, resulting in a decrease in kidney function and contributing to hypertension. The prevalence of hypertension in patients with FD was between 28.4% and 56%, whereas hypertension in patients with chronic kidney disease ranged between 33% and 79%. A study using 24-hour ambulatory blood pressure monitoring (ABPM) to measure blood pressure (BP) indicated a high prevalence of uncontrolled hypertension in FD. Thus, 24-hour ABPM ought to be considered for FD hypertension assessments. Appropriate treatment of hypertension is believed to reduce mortality in patients with FD caused by kidney disease, cardiovascular disease, and cerebrovascular disease because hypertension significantly impacts organ damage. Up to 70% of FD patients have been reported to have kidney involvement, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prescribed for proteinuria are recommended as first-line therapy with antihypertensive drugs. In conclusion, hypertension should be controlled appropriately, given the different morbidity and mortality caused by significant organ involvement in FD patients. Copyright © 2023 Korean Society for Electrolyte and Blood Pressure Research.