Cochleovestibular Manifestations in Fabry Disease

Alberto Ciceran,Sonia De Maio

doi:10.1177/2326409816661354

Abstract

Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT) on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in th...

Highlights

Fabry disease (FD) is an inborn error of glycosphingolipid catabolism and results from the enzymatic deficiency of the a-galactosidase A
A few studies reported the effects of enzyme replacement therapy (ERT) on cochleovestibular symptoms and showed controversial results
Some studies show evidence that hearing loss remained stable with ERT and suggested that it provides some protection for the ear inner epithelium.[3]

Summary

Introduction

Fabry disease (FD) is an inborn error of glycosphingolipid catabolism and results from the enzymatic deficiency of the a-galactosidase A. It produces a progressive accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in multiple tissues and organs, including the ear.[1] The otorhinolaryngologic manifestations such as hearing loss, tinnitus, vertigo, and instability express inner ear damage, in both cochlear and vestibular system. A few studies about the effects of enzyme replacement therapy (ERT) on cochleovestibular symptoms showed controversial results. Cochleovestibular damage was the result of moderate loss of outer hair cells, areas of tectorial membrane collapse, reduction in number of fibers in spiral ganglia in the basal turn with normal cell morphology, atrophy of the stria vascularis and the spiral ligament. Foamy vacuolated deposits (Gb3) in endothelial cells and smooth muscle cells were evident in the internal auditory artery, modiolar vessels, and vas spirale

Cochleovestibular Manifestations

Cochlear and Vestibular Evaluation

Effects of ERT on Cochleovestibular Symptoms

Findings

Conclusion