Hearing improvement in patients with Fabry disease treated with agalsidase alfa.
OBJECTIVE
To describe the nature and prevalence of hearing loss in Fabry disease, and its response to enzyme replacement therapy (ERT) with agalsidase alfa.


METHODS
Fifteen male patients with Fabry disease were enrolled in a randomized, double-blind study and received placebo (n = 8) or ERT (n = 7) with agalsidase alfa for 6 months. This was followed by an open-label extension of 36 months thus far. Alongside this trial, an additional eight men and two women have so far received open-label ERT for between 6 and 30 months. Pure-tone audiometry, impedance audiometry and otoacoustic emission testing were performed at 0 (baseline), 6, 18, 30 and 42 months.


RESULTS
Nine patients (36%) had bilateral and ten (40%) had unilateral high-frequency sensorineural hearing loss (SNHL). Three (12%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only five patients (20%) had normal hearing. The high-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 6.3 dB (p < 0.0001, Wilcoxon matched-pairs). This hearing loss subsequently improved above baseline by 1.5 dB at 18 months (p = 0.07), by 5.0 dB at 30 months (p = 0.006) and by 4.0 dB at 42 months (p = 0.01).


CONCLUSIONS
Significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. Alpha-galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement, however, is gradual, suggesting the need for long-term ERT.
Department of Otolaryngology, Royal Free Hospital, London, UK. danielhajioff@pobox.com
D
D
Hajioff
S
S
Goodwin
R
R
Quiney
J
J
Zuckerman
K D
KD
MacDermot
A
A
Mehta
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy*; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010034:Otitis Media with Effusion / Q000209:etiology; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase