Giant axonal neuropathy is an inherited condition characterized by abnormally large and dysfunctional axons called giant axons. Axons are specialized extensions of nerve cells (neurons) that transmit nerve impulses. Symptoms of the disorder first become apparent in the peripheral nervous system, in which long axons connect the brain and spinal cord (central nervous system) to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. However, axons in the central nervous system are affected as well.

Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Gigaxonin is part of the ubiquitin-proteasome system, which is a process that identifies and gets rid of excess or damaged proteins within cells. In particular, gigaxonin plays a role in the breakdown of neurofilaments, which comprise the structural framework that establishes the size and shape of axons.

Giant axonal neuropathy is a very rare disorder; only about 50 affected families have been described in the medical literature. The condition is thought to be underdiagnosed because its early symptoms resemble those of other, more common disorders affecting the peripheral nervous system, such as Charcot-Marie-Tooth disease.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Published Date: July 01, 2020
Published By: National Institutes of Health