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Original Contribution
June 6, 2001

Enzyme Replacement Therapy in Fabry Disease: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke (Drs Schiffmann, Moore, Weibel, and Brady), and Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases (Drs Kopp, Austin, and Balow), National Institutes of Health, Bethesda, Md; Division of Nephropathology, Armed Forces Institute of Pathology, Washington, DC (Dr Sabnis).

JAMA. 2001;285(21):2743-2749. doi:10.1001/jama.285.21.2743

Context Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease.

Objective To evaluate the safety and efficacy of intravenous α-gal A for Fabry disease.

Design and Setting Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health.

Patients Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by α-gal A assay.

Intervention A dosage of 0.2 mg/kg of α-gal A, administered intravenously every other week (12 doses total).

Main Outcome Measure Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI).

Results Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with α-gal A vs no significant change in the placebo group (P = .02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving α-gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P = .05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving α-gal vs a 16.5% increase for placebo (P = .01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving α-gal A vs 19.5 mL/min for placebo (P = .19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving α-gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P = .02). In patients treated with α-gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight.

Conclusion Intravenous infusions of α-gal A are safe and have widespread therapeutic efficacy in Fabry disease.