Giant Axonal Neuropathy

What is giant axonal neuropathy?

Giant axonal neuropathy is an inherited condition that causes disorganisation of a specific type of protein filaments in nerve cells (neurones). The proteins, called neurofilaments, form a structural framework that helps to define the shape and size of the neurones and is 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, the brain and spinal cord (central nervous system) become involved. This may cause a gradual decline in mental function, loss of control of body movement, and seizures.

How common is giant axonal neuropathy?

Giant axonal neuropathy is a rare disorder; the incidence is unknown.

What genes are related to giant axonal neuropathy?

Mutations in the GAN gene cause giant axonal neuropathy.

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 neurone. Other mutations result in the absence of any functional gigaxonin protein.

neurones 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.

How do people inherit giant axonal neuropathy?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for giant axonal neuropathy?

• GAN
• neuropathy, giant axonal