Progressive hearing (pHL) and vestibular (pVL) loss are frequent deficits in Fabry disease (FD). Recently, enzyme replacement therapy (ERT) with human alpha-galactosidase A has become available. Here, we investigate the association between pHL and pVL in FD and their ERT responses. Pure tone audiometry (PTA) and head impulse testing (HIT) were administered at baseline in 47 patients (25 male, 18-60 y; 22 female, 17-74 y), of whom 24 also received caloric irrigation (CI). Of the 47 patients, 38 (24 male) were tested both before and during ERT (follow- up < or = 60 months). ERT consisted of agalsidase alfa infusions. At baseline, pHL was present in 88% of males and 86% of females. Over all tested frequencies (range: 0.5-6 kHz), pHL was significantly (two-way ANOVA: p < 0.05) greater at higher age and in males,with largest deficits at high frequencies. When assessed with HIT, 80% of males and 77% of females had pVL. pVL was significantly greater at higher age and in males. Tested with CI, 21% of males and 0% of females had pVL. No associations among individual semicircular canal (SCC) deficits, as tested by HIT, and hearing was observed in individual ears. After > or = 18 months of ERT, pVL was significantly smaller than at baseline (ANOVA for HIT: p < 0.01). In contrast, pHL remained unchanged by ERT over 60 months (p > 0.05). We conclude that pHL and pVL prevalences are similar in FD. To detect pVL, HIT is more sensitive than CI. We speculate that pHL and pVL emerge from lesions within the vestibulocochlear labyrinth, because no specific patterns of vestibulo-cochlear deficits were observed, as expected if lesions were more proximal along the inferior or superior branch of the vestibulo-cochlear nerve or labyrinthine artery. Finally, ERT stabilizes auditory and even improves vestibular function.