BACKGROUND: Fabry disease (FD) is a rare genetic disorder of metabolism due to a deficiency of a lysosomal enzyme (alpha-galactosidase A) and the resultant accumulation of globotriasylceramide in the cerebrovascular and cardiovascular systems, kidney, and liver. Symptoms become manifest during childhood or adolescence and progress to include episodes of extremity pains, renal failure, cardiomyopathy, and/or strokes. OBJECTIVES: To better understand quality of life (QOL) in FD patients relative to disease progression, and normatively, compared to other chronic diseases. METHODS: Data were collected prospectively from a sample of 85 FD patients contacted through the Fabry Support and Information Group. Subjects responded to a survey that included the SF-36, a symptoms checklist, and extensive demographic questions. Information about SF-36 performance for other populations was collected from the literature. Data on 53 males are reported here. RESULTS: Patients with FD have substantially lower QOL across all domains compared to the 25th percentile of the general male population, as well as that observed for patients with Gaucher disease, renal disease, and stroke. There is also a very substantial decrease in QOL from early adulthood through middle age (data not shown here). SF-36 Scores