Background-Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population. Methods and Results-Plasma ␣-galactosidase A (␣-Gal) was measured in 79 men with HCM who were diagnosed at Ն40 years of age (52.9Ϯ7.7 years; range, 40 -71 years) and in 74 men who were diagnosed at Ͻ40 years (25.9Ϯ9.2 years; range, 8 -39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at Ͻ40 years had low ␣-Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low ␣-Gal activity had ␣-Gal gene mutations. Conclusion-Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.

These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.