Abstract
Summary: Fabry disease is a rare lysosomal storage disorder resulting from deficient activity of α-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.
Similar content being viewed by others
REFERENCES
Colombi A, Kostyal A, Bracher R, et al (1967) Angiokeratoma corposis diffusum—Fabry's disease. Helv Med Acta 34: 67–83.
Desnick RJ, Ioannou YA, Eng CM (2001) a-Galactosidase A deficiency: Fabry disease. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3733–3774.
Eng CM, Guffon N, Wilcox WR, et al (2001) Safety and efficacy of recombinant human a-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 345: 9–16.
Grewal RP (1993) Psychiatric disorders in patients with Fabry's disease. Int J Psychiatry Med 23: 307–312.
Meikle P, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281: 249–254.
Schiffmann R, Kopp JB, Austin III HA, et al (2001) Enzyme replacement therapy in Fabry disease. A randomized controlled trial. JAMA 285: 2743–2749.
Thurberg BL, Rennke H, Colvin RB, et al (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney 62: 1933–1946.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guffon, N., Fouilhoux, A. Clinical benefit in Fabry patients given enzyme replacement therapy—A case series. J Inherit Metab Dis 27, 221–227 (2004). https://doi.org/10.1023/B:BOLI.0000028726.11177.8b
Issue Date:
DOI: https://doi.org/10.1023/B:BOLI.0000028726.11177.8b