Anderson-Fabry disease (AFD), an X linked lysosomal storage disorder, results in glycoshingolipid deposition in multiple organ systems, including the heart. Recognised cardiac manifestations include conduction disease, valvar thickening, and left ventricular hypertrophy (LVH).¹ Recent studies have shown that enzyme replacement therapy (ERT) reduces left ventricular (LV) mass in patients with AFD.² It remains uncertain, however, whether LVH is a clinically relevant surrogate marker of disease severity.

Weidemann and colleagues² have shown that tissue Doppler derived strain rate improves during treatment with ERT, suggesting that contractile function is reversibly impaired in AFD cardiomyopathy. To determine the importance of systolic performance in the natural history of AFD we performed a retrospective analysis of an untreated cohort of patients followed for at least one year.

Seventy five patients with AFD were evaluated at the Heart Hospital, London between 1 January 1993 and 1 December 2003. Diagnosis of AFD was based on low plasma α-galactosidase A (α-Gal) concentrations and DNA mutational analysis. The mean (SD) follow up from diagnosis of AFD was 5.8 (4.8) years. Twenty four patients had been followed up for more than one year; 12 were receiving ERT at the time of evaluation. The 12 untreated patients (nine male patients, three female patients, mean age 54.5 (12.2) years, range 42–82 …