Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease

Fabry disease is an X‐linked disorder caused by a deficiency of lysosomal α‐galactosidase A resulting in accumulation of α‐D‐galatosyl conjugated glycosphingolipids. Clinical manifestations include a small‐fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3‐year open‐label extension of a previously reported 6‐month placebo‐controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.2 mg/kg of α‐galactosidase A every 2 weeks. The effect of ERT on neuropathic pain scores while off pain medications, quantitative sensory testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory sweat test (TST) is reported. In the patients who crossed‐over from placebo to ERT (n = 10), mean pain‐at‐its‐worst scores on a 0–10 scale decreased (from 6.9 to 4.5). There was a significant reduction in the threshold for cold and warm sensation in the foot. At the 3‐year time‐point, pre‐ERT sweat excretion in 17 Fabry patients was 0.24 ± 0.33 μl/mm2 vs. 1.05 ± 0.81 in concurrent controls (n = 38). Sweat function improved 24–72 h post‐enzyme infusion (0.57 ± 0.71 μl/mm2) and normalized in four anhidrotic patients. TST confirmed the QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest but significant improvement in the clinical manifestations of the small‐fiber neuropathy associated with this disorder. QSART may be useful to further optimize the dose and frequency of ERT. Muscle Nerve 28: 703–710, 2003