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Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease


Background. Fabry disease is an X-linked genetic disorder resulting in the accumulation of glycosphingolipids in various organs, leading to exercise intolerance and early mortality. Enzyme replacement therapy (ERT) has recently been approved for use in Fabry patients. Goals of study. To assess baseline cardiopulmonary exercise characteristics in both invasive and noninvasive tests and to study the impact of ERT on exercise. Methods. A total of 15 patients with Fabry disease underwent baseline cardiopulmonary exercise tests. Six patients were randomized 2:1 to receive either ERT or placebo. We performed serial cardiopulmonary exercise tests at baseline and every 3 months over a period of at least 18 months. The baseline test was compared to the last two exercise tests for each patient. Results. Mean age was 32 years. Mean VO2 max was 1.680 ± 0.67 L/min and increased by 0.459 ± 0.64 L/min in the patients receiving ERT. Mean VO2 max was 1.462 ± 0.25 L/min and decreased by 0.116 ± 0.44 L/min in patients on placebo. Mean oxygen pulse (VO2/HR) increased by 1.71 with enzyme, but increased only 0.025 in patients taking placebo. Estimated stroke volume (SV) increased by 10 ml in patients on ERT. Conclusions. In this small cohort, exercise tolerance increased in patients receiving enzyme replacement therapy. Cardiopulmonary exercise testing is a useful test in measuring the response to therapy in Fabry disease patients.

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anaerobic threshold


cardiac output


diffusing capacity to alveolar volume ratio


average diffusing capacity


enzyme replacement therapy


forced expiratory fraction from 25% to 75% of the total exhalation


forced expiratory volume in one second


forced vital capacity


heart rate


stroke volume


dead space to tidal volume ratio


minute ventilation per CO2 production


maximum oxygen uptake measured at peak exercise


mean oxygen pulse


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Correspondence to Gregory Bierer.

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Communicating editor: Douglas Brooks

Competing interests: W. R. Wilcox is a paid consultant of Genzyme Corp. and is on the Genzyme Speakers Bureau. Neither he nor his relations own Genzyme stock. Genzyme Corp. provided a research grant for the study

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Bierer, G., Balfe, D., Wilcox, W.R. et al. Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease. J Inherit Metab Dis 29, 572–579 (2006).

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  • Enzyme Replacement Therapy
  • Fabry Disease
  • Anaerobic Threshold
  • Cardiopulmonary Exercise
  • Cardiopulmonary Exercise Test