Enzyme replacement therapy and intraepidermal innervation density in Fabry disease.
We prospectively evaluated the effect of enzyme replacement therapy (ERT) on the intraepidermal nerve fiber density (IENFD) and thermal threshold in patients with Fabry disease, an X-linked disorder associated with a painful small-fiber neuropathy and decreased linear IENFD in a length-dependent pattern. Twenty-five hemizygous male patients with Fabry disease were enrolled in a 6-month, randomized, placebo-controlled ERT trial of 0.2 mg/kg of alpha-galactosidase A (agalsidase-alfa) every 2 weeks followed by an additional 12 months of open-label ERT for both populations. IENFD and thermal threshold were measured in the distal thigh at baseline, 6 months, and 18 months from initiation of the trial. We found no significant difference in IENFD between the treatment groups at 6 months. After an additional year of ERT, there was a significant reduction in IENFD in the patient group as a whole, attributable to the declining glomerular filtration rate. Thermal thresholds remained unchanged. We conclude that epidermal nerve fiber regeneration, as measured in the distal thigh, does not occur in this patient population after 12-18 months of ERT.
Developmental and Metabolic Neurology Branch, NINDS, National Institutes of Health, Bldg. 10, Room 3D03, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. RS4e@nih.gov
Raphael
R
Schiffmann
Peter
P
Hauer
Barbara
B
Freeman
Markus
M
Ries
Leland J C
LJ
Scott
Michael
M
Polydefkis
Roscoe O
RO
Brady
Justin C
JC
McArthur
Kathryn
K
Wagner
D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004817:Epidermis / Q000294:innervation*; D005069:Evaluation Studies as Topic; D000795:Fabry Disease / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers; D011446:Prospective Studies; D012684:Sensory Thresholds / Q000528:radiation effects; D013697:Thermosensing / Q000187:drug effects; D013997:Time Factors; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D000519:alpha-Galactosidase