Clinical benefit in Fabry patients given enzyme replacement therapy--a case series.

Fabry disease is a rare lysosomal storage disorder resulting from deficient activity of alpha-galactosidase A and subsequent pathological accumulation of glycosphingolipids throughout the body. Traditionally, Fabry disease was managed symptomatically, but the introduction of enzyme replacement therapies (ERTs) (agalsidase beta (Fabrazyme); agalsidase alfa (Replagal)) has transformed treatment of this disorder. Clinical studies of both compounds have demonstrated clearance of glycosphingolipds from key tissues. To explore whether substrate clearance translates into clinical benefit, a retrospective survey of 17 patients (mean age 34.7 years) treated with agalsidase beta (1 mg/kg every 2 weeks) was undertaken, using an eight-item retrospective questionnaire developed specifically to assess the effect of ERT on the symptoms of Fabry disease. Pain severity, heat tolerance, physical activity, fatigue and psychological status were scored using a 10-point visual analogue scale (e.g. for pain severity: 1=none, 10=strong). Answers to all other questions were quantitative. Changes in mean scores were 4.69 to 2.25 (p =0.012) for pain severity; 4.38 to 2.21 (p =0.019) for number of pain crises per month; 8.69 to 2.98 (p =0.097) for duration of pain crises in hours; 2.76 to 5.76 (p =0.002) for heat tolerance; 3.28 to 2.51 (p =0.058) for bowel movements per day; 2.47 to 4.47 (p =0.007) for frequency of physical activity; 5.53 to 3.71 (p =0.046) for fatigue, and 5.82 to 8.12 (p =0.005) for psychological status. All patients improved in at least one aspect, although the degree of improvement across patients and aspects varied widely; reasons for this remain unclear. Despite the inherent bias involved in retrospective questionnaires, we believe that the findings are encouraging. A prospective version of the questionnaire is currently under validation.