Fabry disease is a rare X-linked deficiency of α-galactosidase A (αgal), which causes glycosphingolipid accumulation. This study analysed the cardiovascular manifestations of a cohort of Fabry patients, and sought to define relationships between disease severity, αgal activity, and cardiac abnormalities.
Methods and results
We prospectively analysed Fabry patients (139 subjects: 92 males and 47 females) undergoing screening for potential enzyme replacement therapy. Baseline echocardiograms, electrocardiograms, and exams were obtained as part of two multinational clinical trials. Cardiovascular symptoms were present in 60.4%. By echocardiography, the mean left ventricular mass index (LVMI) was increased at 165.5 ± 66.9 g/m2, and 84.8% of patients displayed concentric left ventricular hypertrophy (LVH). Electrocardiographic LVH was present in >50% of adult subjects. In females, log-corrected plasma αgal activity was inversely associated with LVMI (r = −0.45, P < 0.040). Males with extremely low αgal activity and renal disease displayed the most LVH and cardiac symptoms, but LVH was prevalent even in females <20 years old.
Concentric LVH was the predominant cardiac pathology seen in patients with Fabry disease, and was prevalent in both genders by the third decade of life. Left ventricular mass index was inversely correlated with αgal activity, but was prevalent even in younger females.
Keywords: Cardiomyopathy, Echocardiography, Genetics, Hypertrophy, Fabry, α-Galactosidase