Enzyme replacement therapy improves function of C-, Aδ-, and Aβ-nerve fibers in Fabry neuropathy

Abstract

Background: Peripheral neuropathy in Fabry disease predominantly involves small nerve fibers. Recently, enzyme replacement therapy (ERT) with recombinant human α-galactosidase A has become available.

Objective: To evaluate whether ERT improves Fabry neuropathy.

Methods: In 22 Fabry patients (age 27.9 ± 8.0 years) undergoing ERT with recombinant human α-galactosidase A (agalsidase beta) for 18 (n = 11) or 23 (n = 11) months and in 25 control subjects (age 29.0 ± 10.4 years), the authors performed quantitative sensory testing using the 4, 2, and 1 stepping algorithm (CASE IV™). Detection thresholds of vibration (VDT) on the first toe were assessed; cold detection thresholds (CDT), heat-pain onset (HP 0.5), and intermediate heat-pain (HP 5.0) assessments were made on the dorsum of the feet. Patient values above mean + 2.5 SD of control values were considered abnormal.

Results: Before ERT, VDT, CDT, HP 0.5, and HP 5.0 were higher in patients than control subjects (p < 0.05). Following ERT, patients developed lower thresholds than prior to ERT for VDT (15.5 ± 3.5 vs 14.3 ± 4.1; p < 0.05), HP 0.5 (22.3 ± 6.7 vs 19.4 ± 1.3; p < 0.01), and HP 5.0 (27.3 ± 5.6 vs 22.5 ± 2.3; p < 0.01). Moreover, fewer patients had abnormal results of VDT (2 vs 4), CDT (7 vs 12), HP 0.5 (0 vs 9), and HP 5.0 (4 vs 20) after than before ERT.

Conclusions: ERT therapy with agalsidase beta significantly improves function of C-, Aδ-, and Aβ-nerve fibers and intradermal vibration receptors in Fabry neuropathy. Lack of recovery in some patients with abnormal cold or heat-pain perception suggests the need for early ERT, prior to irreversible nerve fiber loss.