Abstract
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.