Cardiac abnormalities in Fabry disease: Natural history in hemizygote males suggests that cardiac pathology is universally present

The purpose of the current study is to describe the natural history of cardiac involvement in Fabry disease and assess prevalence of primary, intrinsic causes of cardiac hypertrophy versus secondary causes, as well as the frequency of acute cardiac events in a large cohort of hemizygous patients. All hemizygous male patients diagnosed and evaluated at the National Institutes of Health during the years 1983-2000, were included in this retrospective analysis. Cardiac function was evaluated by 12-lead electrocardiogram (ECG) and 2-dimensional echocardiography (2-D ECHO) every 6 months over 3-17 years. Eighty-six hemizygous patients were evaluated. Mean values on ECG for PR, QRS, and QT intervals were within normal limits; in 54/84 (64%) patients who underwent ECG at presentation there were signs of left ventricular hypertrophy (LVH). No patient younger than 10 years had an ECG abnormality, but 50% of patients aged 45 years did have some abnormality. In 25/ 86 patients (29%) there was echocardiographic evidence of LVH; 50% of patients aged 40 years had some abnormality. The current study does not support the thesis of a correlation between enzyme levels and cardiac or renal markers for Fabry disease. Therefore, one cannot posit that slightly elevated endogenous enzyme is predictive of a milder course; this is comparable to other lysosomal storage disorders. An alternative explanation may be that cardiac involvement is the sine qua non of Fabry disease, and hence will be seen in all patients in an age-related association.