Hearing loss in Fabry disease: The effect of agalsidase alfa replacement therapy

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.