LAUSR

Introduction: The genetic mutation IVS4+919G>A commonly found among Chinese is associated with later-onset cardiac variant of Fabry disease (FD). Patients with left ventricular hypertrophy (LVH) may be screened for FD by measuring plasma α-galactosidase activity. Objective: The aim of our study is to determine the prevalence of FD among Chinese LVH patients and to define demographic and echocardiographic predictors of FD. Methods: We measured plasma α-galactosidase activity using dried blood spot test in 500 Hong Kong Chinese patients with LVH (defined as maximal left ventricular septal or posterior wall thickness ≥13 mm on transthoracic echocardiography). LVH and deficiency in α-galactosidase activity prompted genetic analysis of galactosidase alpha gene. Demographic and echocardiographic predictors of FD were analysed. Results: There are 9 (1.8%) of 500 LVH patients (all men, age 53–74 years) had low α-galactosidase activity (0.64±0.32 μmol/L wb/hr) and all were confirmed to have the FD genotype IVS4+919G>A. Among these 9 FD patients, 6 (66.7%) could be traced to the ancestral home Chaozhou (southern part of China), 4 had hypertension, but none exhibited extracardiac manifestations of FD. The left ventricular mass of FD patients ranged from 64.91–811.81 g. Ancestral home Chaozhou (odds ratio, 10.28; 95% confidence Interval, 2.52–41.94; p=0.001) and LVM ≥290 g (odds ratio, 7.39; 95% confidence Interval, 1.94–28.20; p=0.003) were predictors of FD. On receiver operating characteristic curve analysis, sensitivity and specificity of LVM ≥290 g to diagnose FD vs non-FD LVH are 67% and 86.4% respectively (area under curve, 0.8; p=0.002). Conclusion: There is a high prevalence of later-onset cardiac variant FD among Hong Kong Chinese LVH patients that is associated with IVS4+919G>A genotype. Male patients with ancestral home Chaozhou and LVM ≥290 g are at an increased risk of FD among Chinese LVH patients and should be screened with dried blood spot test.