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

Introduction: Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce.

Methods: 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.

Results: 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.

Conclusion: 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.