title: Hearing loss in Fabry disease: the effect of agalsidase alfa replacement therapy.
abstract: The aim of this study was to describe the nature and prevalence of hearing loss in Fabry disease (McKusick 301500), a rare X-linked lysosomal storage disorder, and its response to enzyme replacement therapy with agalsidase alfa. Fifteen hemizygous male Fabry patients (aged 25-49 years) were randomized to receive placebo or enzyme replacement therapy for 6 months; all have received open-label enzyme replacement therapy for an additional 24 months thus far. Pure-tone audiometry, impedance audiometry and otoacoustic emission testing were performed at 0 (baseline), 6, 18 and 30 months. Four patients (27%) had bilateral and 7 (47%) had unilateral high-frequency sensorineural hearing loss (SNHL). Two (13%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only 3 (20%) had normal hearing. High-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 4.3 dB ( p =0.002, Wilcoxon matched pairs). This hearing loss subsequently improved above baseline by 2.1 dB at 18 months ( p =0.02) and by 4.9 dB at 30 months ( p =0.004). In conclusion, 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 is gradual, however, suggesting the need for long-term enzyme replacement therapy.
authors.affiliation: Department of Otolaryngology, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hajioff
authors.forename: Y
authors.initials: Y
authors.lastname: Enever
authors.forename: R
authors.initials: R
authors.lastname: Quiney
authors.forename: J
authors.initials: J
authors.lastname: Zuckerman
authors.forename: K
authors.initials: K
authors.lastname: Mackermot
authors.forename: A
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy*; D006314:Hearing Loss, Conductive / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase