Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy.
BACKGROUND
Peripheral neuropathy in Fabry disease predominantly involves small nerve fibers. Recently, enzyme replacement therapy (ERT) with recombinant human alpha-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 alpha-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-, Adelta-, and Abeta-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.
Hilz
M J
MJ
Department of Neurology, New York University School of Medicine, NY 10016, USA. max.hilz@neuro.med.uni-erlangen.de
Brys
M
M
Marthol
H
H
Stemper
B
B
Dütsch
M
M
D000328:Adult; D003080:Cold Temperature; D003943:Diagnostic Techniques, Neurological; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D009460:Neurologic Examination; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014732:Vibration; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D011994:Recombinant Proteins; D000519:alpha-Galactosidase