Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

摘要

Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of glycolipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at a young age. Neuropathic pain and pain attacks are often the presenting symptoms of the disease and start at an average age of 9 years in male patients and 16 years in female patients, but currently a systematic literature review in early childhood showed the presence of these symptoms before the age of 5 years. Clinical studies have shown that enzyme replacement therapy may improve the overall pain scores and pain intensity in patients; improvements in pain outcomes have been sustained during the long-term follow-up, allowing many patients to reduce their use of pain medication. Some indirect evidence from dose-switching studies suggests that enzyme replacement therapy dose may be of relevance to pain outcomes. Considering that damage to small nerve fibers occurs early, prompt treatment is important in order to limit damage to the peripheral nervous system. In this article a comprehensive overview of the existing literature on small nerve fiber pathophysiology and the relationship with neuropathic pain and treatment response in children and adults with Fabry disease is presented.