Giant axonal neuropathy

Giant axonal neuropathy is a rare inherited condition that causes disorganization of neurofilaments. Neurofilaments form a structural framework that helps to define the shape and size of neurons and are essential for normal nerve function.

Giant axonal neuropathy generally appears in infancy or early childhood, and slowly progresses as more cells become involved. Signs of giant axonal neuropathy usually begin in the peripheral nervous system, which controls the arms, legs and many other areas of the body. Most individuals with this disorder first have problems with walking. Later they may lose sensation, coordination, strength, and reflexes in their limbs. Hearing or vision problems may also occur. Extremely kinky hair is characteristic of giant axonal neuropathy, appearing in almost all affected people. As the disorder progresses, central nervous system becomes involved. This may cause a gradual decline in mental function, loss of control of body movement, and seizures.

Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Some GAN mutations affect the shape of the protein, changing how it binds to others in organizing the structure of the neuron. Other mutations result in the absence of any functional gigaxonin protein.

Neurons affected by a mutated GAN gene accumulate excess neurofilaments in the axon, the long extension from the nerve cell that transmits its signal to other nerve cells and to muscles. These distended or giant axons do not transmit signals properly and eventually deteriorate, resulting in problems with movement and other nervous system functions. The disease is inherited in an autosomal recessive pattern which means both parents must have mutated GAN genes.

This article incorporates public domain text from The U.S. National Library of Medicine