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. 2002 Oct 11:3:10.
doi: 10.1186/1471-2350-3-10.

Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

Dominique P Germain  1 , Paul Avan, Augustin Chassaing, Pierre Bonfils
Affiliations

Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

Dominique P Germain et al. BMC Med Genet. .

Abstract

Background: Fabry disease (FD, OMIM 301500) is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement.

Methods: We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19-64 years, mean 39) affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy.

Results: A total of 12 patients (54.5%) with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32%) experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P < 0.01) or cerebrovascular lesions (P < 0.01), whereas there was no correlation with left ventricular hypertrophy. In addition, tinnitus aurium was also found in six patients (27%).

Conclusion: This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s) of the cochlear involvement deserves further studies.

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Figures

Figure 1
Figure 1
Degree of hearing loss as a function of age in 22 patients affected with Fabry disease. Impairment was classified using pure-tone thresholds (0.5, 1, and 2 kHz; PTAs) on the more affected ear without any consideration with the age or higher frequencies (4 and 8 kHz).
Figure 2
Figure 2
Comparison of thresholds for 20 Fabry hemizygotes, aged 25 years and older (circles), with 95th percentile data (squares) from the International Organization for Standardization 1990 standards for 0.5, 1, 2, 4 frequencies and PTAs or, for 8 kHz, with the 90th percentile. dB HL indicates decibel hearing level.
Figure 3
Figure 3
Percentage of study subjects with pure-tone thresholds above the 95th percentile for the 0.5, 1, 2, 4 frequencies and PTAs, and above the 90th percentile for the 8 kHz frequency
Figure 4
Figure 4
Glomerular filtration rate (GFR) against mean bilateral pure-tone averages (0.5, 1, and 2 kHz) in 22 hemizygotes affected with classic Fabry disease.
See this image and copyright information in PMC

References

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