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 alpha-galactosidase A resulting in accumulation of alpha-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 alpha-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 microl/mm(2) vs. 1.05 +/- 0.81 in concurrent controls (n = 38). Sweat function improved 24-72 h post-enzyme infusion (0.57 +/- 0.71 microl/mm(2)) 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.
Schiffmann
Raphael
R
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke/National Institutes of Health, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892-1260, USA. rs4e@nih.gov
Floeter
Mary Kay
MK
Dambrosia
James M
JM
Gupta
Surya
S
Moore
David F
DF
Sharabi
Yehonatan
Y
Khurana
Ramesh K
RK
Brady
Roscoe O
RO
D000328:Adult; D001369:Axons / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology; D004311:Double-Blind Method; D000795:Fabry Disease / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D009460:Neurologic Examination; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000503:physiopathology*; D012018:Reflex / Q000502:physiology; D012677:Sensation; D013546:Sweating / Q000502:physiology*; D014732:Vibration; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D000519:alpha-Galactosidase