Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy

Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce. This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups: classical and non-classical FD patients with or without ERT. To study effects of ERT, longitudinal data, corrected for age and gender according to ISO-1999 guidelines, were analyzed with mixed models. In the cross-sectional analysis, 107 FD patients (41 males), median age 47.6 years (18.8-80.6) were analyzed. At baseline, i.e., before start of ERT, HL was present in 18 patients (16.8 %), of whom four had bilateral sensorineural HL. HL was more often present in patients with the classical phenotype than non-classical patients (p  < 0.01). Likewise, males had more often HL than females. Compared to the general population, FD patients show a median HL of 8.2 dB at low frequencies (p  < 0.01) and 29.5 dB at ultra-high frequencies (p  < 0.01). Longitudinal analyses (n = 91) revealed that ERT treated patients show a similar rate of decline, not significantly different from healthy controls. Adult FD patients, especially classical affected males, show impaired hearing. Longitudinal analyses during ERT in these patients demonstrates a decline of HL similar to healthy controls, but HL present before initiation of therapy cannot be reversed. Whether early therapy can prevent hearing loss is unknown