Giant Axonal Neuropathy

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What is giant axonal neuropathy?

Giant axonal neuropathy is an inherited condition that causes disorganization of a specific type of protein filaments in nerve cells (neurons). The proteins, called neurofilaments, form a structural framework that helps to define the shape and size of the neurons 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 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.

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 each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Source: National Institutes of Health

Study findings on neuropathy genetics are outlined in reports from Stanford University

"Geneticists refined the chromosomal interval containing the locus, culminating in the cloning of the defective gene, GAN. To date, many distinct mutations scattered throughout the coding region of the locus have been reported by researchers from different groups around the world. GAN encodes the protein, gigaxonin. Recently, a genetic mouse model of the disease was generated by targeted disruption of the locus. Over the years, the molecular mechanisms underlying GAN have attracted much interest. Studies have revealed that gigaxonin appears to play an important role in cytoskeletal functions and dynamics by directing ubiquitin-mediated degradations of cytoskeletal proteins. Aberrant accumulations of cytoskeletal-associated proteins caused by a defect in the ubiquitin-proteasome system (UPS) have been shown to be responsible for neurodegeneration occurring in GAN-null neurons, providing strong support for the notion that UPS plays crucial roles in cytoskeletal functions and dynamics," wrote Y. Yang and colleagues, Stanford University.

The researchers concluded: "However, many key questions about the disease remain unanswered."

Yang and colleagues published their study in Cellular and Molecular Life Sciences (Giant axonal neuropathy. Cellular and Molecular Life Sciences, 2007;64(5):601-9).

For more information, contact Y. Yang, Stanford University School of Medicine, Dept. of Neurology and Neurological Sciences, Stanford, California 94305-5489 USA.

Publisher contact information for the journal Cellular and Molecular Life Sciences is: Birkhauser Verlag Ag, Viadukstrasse 40-44, PO Box 133, CH-4010 Basel, Switzerland.

Keywords: United States, Stanford, Neuropathy Genetics, Cellular, Genetics, Neuropathy.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.