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Open Access Highly Accessed Research

Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

Saskia M Rombach1, Bouwien E Smid1, Machtelt G Bouwman3, Gabor E Linthorst1, Marcel G W Dijkgraaf2 and Carla E M Hollak1*

Author Affiliations

1 Department of Internal Medicine, Division of Endocrinology and Metabolism, Academic Medical Center, PO Box 22660, Amsterdam, DD, 1100, The Netherlands

2 Clinical Research Unit, Academic Medical Center, PO Box 22660, Amsterdam, DD, 1100, The Netherlands

3 Department of Pediatrics, Academic Medical Center, PO Box 22660, Amsterdam, DD, 1100, The Netherlands

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Orphanet Journal of Rare Diseases 2013, 8:47  doi:10.1186/1750-1172-8-47

Published: 25 March 2013

Abstract

Background

Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness is unclear.

Methods

Renal, cardiac, and cerebral outcomes were prospectively studied in males and females with Fabry disease treated with ERT. Additionally, the occurrence of major cardiac events, stroke, end-stage renal disease and death was compared to a natural history (NH) cohort meeting treatment criteria.

Results

Of 75 patients on ERT (median treatment duration 5.2 years, range 0.05-11.0), prospective follow-up was available for 57 adult patients (30 males) and 6 adolescents. Renal function declined in males (-3.4 ml/min/1.73 m2 per year, SE 0.2; p < 0.001) despite ERT, but followed the normal course in females (-0.8 ml/min/1.73 m2 per year, SE 0.3; p = 0.001). Cardiac mass increased during ERT in males (+ 1.2 gram/m2.7, SE 0.3; p < 0.001), but remained stable in females (-0.3 gram/m2.7 per year, SE 0.4; p = 0.52). ERT did not prevent the occurrence of cerebral white matter lesions. Comparison of ERT treated to untreated patients revealed that the odds to develop a first complication increased with age (OR 1.05 (95% CI: 1.0-1.1) per year, p = 0.012). For development of a first or second complication the odds declined with longer treatment duration (OR 0.81 (95% CI: 0.68-0.96) per year of ERT, p = 0.015;OR 0.52 (0.31-0.88), p = 0.014 respectively).

Conclusions

Long term ERT does not prevent disease progression, but the risk of developing a first or second complication declines with increasing treatment duration. ERT in advanced Fabry disease seems of doubtful benefit.