Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy.
OBJECTIVE
We aimed to study the prevalence of Fabry disease (FD) in patients with hypertrophic cardiomyopathy (HCM).


BACKGROUND
There are limited and controversial data about the prevalence of FD in patients with HCM.


METHODS
We screened the plasma alpha-galactosidase A activity from 508 unrelated patients with HCM (328 men, 180 women, ages 58 +/- 16 years). Patients with low activity (0% to 30% of the normal control in men, and 0% to 50% in women) underwent genetic study of the GLA gene.


RESULTS
We found low plasma activity in 15 patients (3%). Three men had GLA mutations (0.9%): S238N (novel) in 2 and E358del (described) in 1. Two women had described mutations (1.1%): L89P and A143T. Three unrelated men had the D313Y variant previously associated with enzyme pseudo-deficiency. Two women had polymorphisms that did not segregate with the disease in their families. Five women (activity 39% to 47%) had no sequence variants. The familial studies allowed the diagnosis of 14 carriers: 6 women without Fabry manifestations, 3 women with cardiomyopathy, 2 men with renal and cardiac disease, 1 man with microhematuria, 1 woman with first-degree atrioventricular block, and a 32-year-old woman with only renal disease.


CONCLUSIONS
By means of a screening based on genotyping of patients with low plasma enzymatic activity, the prevalence of FD in our population of HCM is 1% (0.9% in men and 1.1% in women). This diagnosis is relevant, because it allows the identification of disease carriers that might benefit from enzyme replacement therapy.
D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D000519:alpha-Galactosidase / Q000235:genetics
D000519:alpha-Galactosidase