What are the other Names for this Condition? (Also known as/Synonyms)

• GAN (Giant Axonal Neuropathy)

What is Giant Axonal Neuropathy? (Definition/Background Information)

• Giant Axonal Neuropathy (GAN) is an inherited genetic condition wherein there is an abnormal functioning of nerve cells, due to accumulation of abnormal neurofilaments protein. Neurofilaments are proteins that are required for proper nerve cell function
• In Giant Axonal Neuropathy, abnormal neurofilaments result in dysfunctional axons (part of nerve cells). Axons and neurofilaments are important in transmitting nerve signals back and forth in the body
• Due to this abnormal nerve function, a variety of signs and symptoms related to this can be noted. The signs and symptoms include difficulty walking, seeing, perceiving sensation, and poor muscle strength and reflexes
• Giant Axonal Neuropathy is a progressive and degenerative disorder that can only be managed through proper supportive therapy. However, the prognosis of the disorder is poor

Who gets Giant Axonal Neuropathy? (Age and Sex Distribution)

• Giant Axonal Neuropathy is a very rare congenital condition that is usually manifested in infancy or during early childhood
• Both male and female genders are prone to this disorder
• The disorder is observed worldwide and all racial and ethnic groups are at risk

What are the Risk Factors for Giant Axonal Neuropathy? (Predisposing Factors)

• A positive family history of Giant Axonal Neuropathy is the only known risk factor for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Giant Axonal Neuropathy? (Etiology)

• Giant Axonal Neuropathy is a genetic disorder that is inherited in an in an autosomal recessive pattern
• In this disorder, there are genetic mutations in the GAN gene, which is responsible for the production of a protein (gigaxonin)
• Due to the abnormal mutations, other proteins (neurofilaments) get accumulated within the nerve cell, which affect their function
• The abnormal deposition of proteins within the nerves causes the nerve cells to become large; this obstructs their ability to carry nerve impulses efficiently, resulting in the various signs and symptoms

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Giant Axonal Neuropathy?

The signs and symptoms of Giant Axonal Neuropathy may include:

• Abnormal nerve function causing difficulties in walking, perceiving sensation, difficulty in reflexes and inadequate muscle strength
• Since the nerves are fundamental to hearing and vision, there are signs and symptoms related to these such as vision and hearing difficulties
• Some individuals may have an extremely curvy hair (kinky hair)
• The central nervous system (CNS) may be affected presenting signs and symptoms such as decreased mental function, loss of control of body movements, and seizures

The clinical indications of GAN gradually worsen as the baby grows and develops.

How is Giant Axonal Neuropathy Diagnosed?

Giant Axonal Neuropathy may be diagnosed using the following tools:

• Complete physical examination with evaluation of medical history
• This includes screening of the newborn baby having a family history the disorder, which is very important
• MRI scan of the brain
• Biopsy of the peripheral nerve
• Nerve conduction velocity; to examine speed of nerve (electrical) signals
• Molecular genetic testing
• Prenatal exams include amniocentesis and chorionic villus sampling to detect GAN mutations

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Giant Axonal Neuropathy?

Complications due to Giant Axonal Neuropathy increase in intensity over time, since it is a degenerative disorder affecting the central nervous system and brain. The complications may include:

• Difficulty walking, moving slowly leading to a condition of quadriplegia (complete paralysis of body and limbs) due to progressive brain and spinal cord injuries
• Seizures, loss of sensation, complete body function; individuals would require full assistance for eating, mobility

How is Giant Axonal Neuropathy Treated?

Giant Axonal Neuropathy is a genetic disorder that has no known cures. An individualized treatment (a case-by-case approach) is planned and provided to improve the quality of life, based on the specific conditions/complications that develop:

• The primary goal of treatment is to preserve neurological function to the extent possible, by working on increasing the physical and mental development of the child
• In order to improve the motor skills and mental abilities; special therapeutic treatment (by speech, physical and occupational therapists) with supportive care may be required
• The next goal is to provide symptomatic management of the condition and reduce the effects of nervous system degeneration over time

How can Giant Axonal Neuropathy be Prevented?

• Currently, there are no specific methods or guidelines to prevent Giant Axonal Neuropathy, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as GAN
• Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory; often several years of active vigilance is necessary

What is the Prognosis of Giant Axonal Neuropathy? (Outcomes/Resolutions)

• Giant Axonal Neuropathy is a fatal genetic disorder involving the central nervous system that causes a gradual deterioration of the body system
• The initial years may be normal; however, as time passes most children suffer a progressive collapse of the nervous system and the brain, causing total physical and mental paralysis with complete loss of body functions
• Death inevitably occurs after in the late teenage or early adult phase

Additional and Relevant Useful Information for Giant Axonal Neuropathy:

There are voluntary organizations and support groups that provide help and understanding to the families and parents of the Giant Axonal Neuropathy disorder affected.