Giant axonal neuropathy

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 6, 2016
StartDiseasesGiant axonal neuropathy

Giant axonal neuropathy is an exceptionally rare congenital disorder with a wide range of debilitating symptoms that affect voluntary and involuntary muscle control. Giant axonal neuropathy involves abnormalities of axons which are the parts of neurons that deliver impulses. It affects both the central nervous system (the brain and the spinal cord) and the peripheral nervous system.

Contents

Definition & Facts

Giant axonal neuropathy (GAN) is a rare, inherited genetic disorder that is an early-onset and fatal disease that slowly causes impairment and the degeneration of the peripheral as well as central nervous systems. It is a neurodegenerative disorder that results in the loss of basic functions. Giant axonal neuropathy begins at infancy and most people with this disease do not live past their twenties.

Unfortunately because this condition is so rare, funding for research into this disease is less robust than it is for more common diseases.

Symptoms & Complaints

Most children that are born with giant axonal neuropathy (GAN) will begin to demonstrate symptoms around or before the age of 5. Symptoms of giant axonal neuropathy typically begin in the peripheral nervous system of the body, which is responsible for controlling movement, feeling and sensation in the arms and legs. Impairment of the peripheral nervous system can manifest itself in the following ways:

As symptoms persist and worsen, most individuals with GAN will become wheelchair dependent in their early to mid 20s. Wheelchair dependence tends to further weaken the body and increased muscle atrophy occurs rapidly as a result, rendering most patients bedridden and immobile. Most patients with this disorder pass away by their thirties typically due to respiratory failure.

Causes

Giant axonal neuropathy is caused by genetic mutations of the GAN gene which make a protein called gigaxonin. There are 20 different genetic mutations associated with this condition. Gigaxonin is a cytoskeletal protein. These mutations result in fewer gigaxonin which increases the amount of neurofilaments which are typically broken down by gigaxonin. These neurofilaments overcrowd the axon cells which results in their destruction. Restricted movement and depleted sensation result from the deterioration of the axons.

The mutations that cause this disorder are inherited through the autosomal recessive inheritance pattern. This means that the child has to inherit two copies of the genetic mutation from genetic carriers who themselves do not have the disease; both parents must be carriers.

Diagnosis & Tests

Diagnosis will involve an intake of medical history and physical history as well as a physical examination. One common physical trait of those with giant axonal neuropathy is that they tend to have extremely curly hair even when their parents do not. They may also be pale, have red hair, and a high forehead.

Giant axonal neuropathy is also diagnosed professionally with a series of tests and can be detected in a variety of different ways, including:

Giant axonal neuropathy is detected when results from a nerve conduction studies show moderate to low speeds of conduction, indicating that the axons are heavy and weighed down with dense cell material and are unable to function.

Treatment & Therapy

There is no definitive treatment for giant axonal neuropathy. However, there are therapies that can help ease the side effects of giant axonal neuropathy. It is recommended that families work together with a medical team that includes the following team of professionals:

  • Pediatric neurologist
  • Orthopedic surgeon
  • Physiotherapist
  • Psychologist
  • Speech therapist
  • Occupational therapists

Speech therapy, physical therapy, occupational therapy, psychotherapy, and counseling all play a role in improving the quality of life of a patient with giant axonal neuropathy. Hearing aids and eyeglasses will be used to address the hearing and vision problems associated with this condition. Special education may also be necessary for children with learning disabilities and cognitive deficits caused by this condition.

According to Hannah's Hope Fund, a charity that raises money for research into giant axonal neuropathy clinical trials are underway in which a virus is used to transmit a healthy GAN gene into nerve cells. This process involves the virus binding to the surface of the cell. The DNA of the virus will invade the nucleus of the nerve cell and express the missing protein. The first patient to undergo this form of gene therapy occurred in 2015. Though still highly experimental, such clinical trials offer hope for patients and families with this exceptionally rare and deadly disease.

Prevention & Prophylaxis

Because giant axonal neuropathy is a genetic, congenital disorder, it cannot be prevented. Much of the current research being done around giant axonal neuropathy focuses on improving, preventing, treating and eventually finding a cure for this rare neurological disease that still proves fatal to those who will experience it.