Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease

Area of Science:

• Neurology
• Genetics
• Otolaryngology

Background:

• Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by glycosphingolipid accumulation.
• Neuro-otologic manifestations like hearing loss and vestibular dysfunction are known but poorly understood in FD.
• Limited data exists on the frequency and mechanisms of these symptoms, and their relation to peripheral neuropathy.

Purpose of the Study:

• To investigate the prevalence of auditory and vestibular symptoms in FD patients.
• To assess neurophysiological involvement of the VIII cranial nerve.
• To correlate neuro-otologic findings with peripheral neuropathy characteristics.

Main Methods:

• A cohort of 36 FD patients underwent comprehensive neurological and neuro-otologic assessments.
• Evaluations included nerve conduction studies, quantitative sensory testing (QST), VEMP, videonystagmography, audiometry, and BAEPs.
• Peripheral neuropathy and small fiber involvement were assessed using neurophysiological and QST methods.

Main Results:

• Neuro-otologic symptoms (hearing loss, vertigo) were reported by a significant portion of patients.
• Auditory or vestibular dysfunction was identified in 75% of participants.
• Small fiber neuropathy was prevalent (77.7%), but no correlation was found between neuro-otologic abnormalities and QST findings.
• The mechanism for cochlear/vestibular dysfunction remained unclear in 70% of cases.

Conclusions:

• Neuro-otologic involvement is common and often underdiagnosed in Fabry disease.
• The damage appears to be multi-systemic, affecting end organs rather than solely neural or vascular pathways.
• Small fiber neuropathy is an early sign of FD, but its progression does not directly correlate with neuro-otologic deficits.