Neurological complications in Fabry disease

Area of Science:

• Neurology
• Genetics
• Metabolic Disorders

Background:

• Fabry disease is a genetic disorder caused by alpha-galactosidase A deficiency.
• This deficiency leads to glycosphingolipid accumulation in various tissues, including the nervous system.
• Cerebrovascular dysfunction and stroke are significant risks in Fabry disease patients.

Purpose of the Study:

• To investigate the extent of small fiber dysfunction in Fabry disease.
• To evaluate the impact of enzyme replacement therapy (ERT) on small fiber neuropathy and associated symptoms.

Main Methods:

• Quantitative sensory testing was used to assess cold and heat-pain detection thresholds.
• Nerve conduction velocities were measured to evaluate large fiber function.
• Patients were assessed before and after 18-23 months of ERT.

Main Results:

• Patients with Fabry disease exhibited reduced cold and heat-pain detection thresholds, indicating prominent small fiber dysfunction.
• Nerve conduction velocities showed only mild reductions, suggesting less significant large fiber involvement.
• ERT treatment led to improvements in small fiber neuropathy and neuropathic pain.

Conclusions:

• Small fiber dysfunction is a primary neurological complication in Fabry disease, contributing to pain and autonomic dysfunction.
• ERT is effective in ameliorating small fiber neuropathy and neuropathic pain, likely through glycosphingolipid reduction.
• These findings highlight the importance of addressing small fiber dysfunction in Fabry disease management.