Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease

Abstract

Background: Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.

Objective: To examine hearing loss in patients with FD depending on cardiac and renal function.

Material and methods: Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA6 (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.

Results: Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05).

Conclusions: High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.

Conflict of interest statement

Competing Interests: DO received speaker's honoraria from Sanofi-Genzyme and travel assistance from Sanofi-Genzyme and Shire. JM received travel assistance from Sanofi-Genzyme, Shire and Amicus. PN received travel assistance, speaker's/advisory board honoraria, and research support from Amicus, Sanofi-Genzyme and Shire. CW received travel assistance, speaker's/advisory board honoraria, and research support from Actelion, Protalix, Sanofi-Genzyme and Shire. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflicts of interest.

Figures

Fig 1. Mean pure tone audiometry thresholds show a high frequency sensorineural hearing loss measured for each right (R) and left (L) ear (n = 68).

Air conduction (AC, circles), bone conduction (BC, triangle). Error bars depict standard deviation.

Fig 2. Averaged pure tone thresholds PTA4 and HF-PTA of all FD patients (n = 68) compared to age specific median thresholds of healthy controls.

Normal thresholds (HF-PTA: black line, PTA4: grey line) decline with age. After adjusting for age, FD patients show highly increased thresholds in PTA4 (grey circles) and significantly increased thresholds in HF-PTA (black triangles).

Fig 3

Air conduction pure tone thresholds of the bad ear (n = 68) in relation to renal (A) and cardiac (B) function. A pronounced increase of hearing threshold at higher frequencies is shown, depending on the severity of renal function, evaluated by the GFR (ml/min/1.73 m2) and graduated in four groups (≥90, 60–89, 30–59 and ≤ 29) and cardiac function, classified by the NYHA class (0, 1, 2, 3).

Fig 4

Mean PTA6 (0.5, 1, 2, 4, 6, 8 kHz) AC thresholds for the bad ear (n = 68) in correlation to (A) GFR (ml/min/1.73 m2, graduated in four groups: ≥90, 60–89, 30–59 and ≤ 29) and (B) NYHA class (0, 1, 2, 3). Asterisks indicate p<0.05. Error bars depict standard deviation.

Fig 5

Click-ABR of the patient’s bad ear (n = 63) according to (A) renal and (B) cardiac function. Renal function was evaluated by GFR (ml/min/1.73 m2) and graduated in four groups (≥90, 60–89, 30–59 and ≤ 29). Cardiac function was classified by NYHA class (0, 1, 2, 3). Asterisks indicate p<0.05. Error bars depict standard deviation.

Fig 6. Mean speech audiometry results in quiet (“Freiburger monosyllables speech test” at 65 dB SPL).

Only the results of the bad ear (n = 65) are shown. (A) Renal function evaluated by the GFR (ml/min/1.73 m2) and graduated in four groups (≥90, 60–89, 30–59 and ≤ 29). (B) Cardiac function was classified by the NYHA score (0, 1, 2, 3). Asterisks indicate p<0.05. Error bars depict standard deviation.