Association of Fabry Disease with Hearing Loss, Tinnitus, and Sudden Hearing Loss: A Nationwide Population-Based Study

Abstract

Hearing loss and the related otologic manifestations are receiving increased scrutiny as significant causes of morbidity in Fabry disease. However, the relative risks of auditory deficits among patients with Fabry disease relative to the general population without a diagnosis of Fabry disease have not been studied. This study aims to explore the associations between Fabry disease and hearing-related manifestations using a nationwide population-based dataset. We identified study patients for this cross-sectional study from the 2015–2017 claims databases of the Taiwan Longitudinal Health Insurance Database 2005. We first identified 2312 patients aged over 20 years with a diagnosis of Fabry disease. We used propensity score matching to select five comparison patients per patient with Fabry disease and 11,560 comparison patients without Fabry disease. We used multivariable logistic regressions to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for tinnitus, hearing loss, and sudden deafness among Fabry disease patients vs. comparison patients. Chi-square tests showed statistically significant differences between patients with and without Fabry disease in the prevalence rates of tinnitus (16.7% vs. 11.7%, p < 0.001), hearing loss (7.5% vs. 6.2%, p = 0.014) and sudden deafness (1.7% vs. 1.0%, p = 0.005). Multiple logistic regression revealed that patients with Fabry disease were more likely to suffer from tinnitus, hearing loss and sudden deafness, with adjusted odds ratios of 1.513 (95% CI = 1.336–1.713), 1.246 (95% CI = 1.047–1.483), and 1.681 (95% CI = 1.166–2.423), respectively. We found that Fabry disease is significantly associated with certain auditory manifestations, including hearing loss, sudden deafness, and tinnitus.

Increased prevalence of peripheral vestibular disorder among patients with Fabry disease

“…The anatomic site of vestibulo-cochlear damage in Fabry disease is not known. Although otological symptoms are quite common in patients with Fabry disease [2], there is only one documented report on human temporal bone pathology in the world [21]. In their first patient, the utricles and vestibules revealed no morphological abnormalities, but in the non-ampullated end of the superior semicircular canal, new bone filled the perilymphatic space in the first patient.…”

“…Fabry disease, also known as Anderson-Fabry disease, is a rare and progressive X-linked glycosphingolipidosis occurring exclusively among males, with documented prevalence rates ranging from 1:8,454 males to 1:117,000 worldwide [1]. These estimates may be on the lower side because screening in newborns show rates ranging from one in 8800 male newborns to 1:600 to 1:1250 reported in Taiwan [2]. Fabry disease is caused by mutations in the GLA gene at Xq21.3-q22, which encodes the alpha-galactosidase, an enzyme responsible for breaking down toxic alpha-galactose groups formed from glycoproteins and glycolipids.…”

“…Thus far, the relative risk of the PVD in Fabry disease patients compared to the general population without Fabry disease has not been studied. Given the high prevalence of Fabry disease in East Asia reported in the recent literature [2], and shared pathogenic pathways between Fabry disease and vasculopathy, we used a nationwide population-based dataset to compare the prevalence of PVD among patients with Fabry disease and matched comparison patients with similar vascular risk factors such as hypertension, coronary heart disease and hyperlipidemia.…”

Increased prevalence of hearing loss, tinnitus and sudden deafness among patients with Sjögren’s syndrome

“…One previous Epidemiology Epidemiology Epidemiology study has used the same ICD codes to examine the association of Fabry disease with hearing loss, tinnitus and sudden hearing loss. 11 In Taiwan, otolaryngologists play a key role in the management of patients with hearing and balance disorders. Usually, the diagnosis and quantification of hearing loss involves air-conduction and boneconduction pure tone audiometry tests in a soundproof room.…”

“…Finally, one study using the same dataset LHID2010 has also reported an association of Fabry disease with hearing loss, tinnitus and sudden hearing loss. 11…”