Neuropathy, giant axonal

Giant Axonal Neuropathy Giant Axonal Neuropathy (GAN) is a rare, inherited neurological disorder characterized by the progressive degeneration of the nervous system. It primarily affects the peripheral nerves, which are responsible for transmitting signals between the brain and spinal cord and the rest of the body. This condition is typically diagnosed in early childhood and can lead to severe physical disabilities.

Clinical Features

Patients with Giant Axonal Neuropathy often present with a variety of symptoms, including:

• Muscle Weakness: Progressive weakness, particularly in the legs, leading to difficulty walking.
• Sensory Loss: Loss of sensation, especially in the extremities.
• Ataxia: Lack of voluntary coordination of muscle movements.
• Cranial Nerve Involvement: May include optic atrophy and hearing loss.
• Curly Hair: A distinctive feature is the presence of tightly curled hair, which can aid in diagnosis.

Pathophysiology

The hallmark of GAN is the presence of giant axons, which are swollen nerve fibers filled with disorganized neurofilaments. This abnormal accumulation disrupts normal nerve function. The condition is caused by mutations in the GAN gene, which encodes the protein gigaxonin. Gigaxonin is involved in the degradation of intermediate filaments, and its dysfunction leads to the accumulation of these filaments within axons.

Genetics

Giant Axonal Neuropathy is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers, who have only one copy of the mutation, typically do not show symptoms.

Diagnosis

Diagnosis of GAN is based on clinical evaluation, family history, and genetic testing. Nerve biopsy may reveal the characteristic giant axons. Genetic testing can confirm mutations in the GAN gene.

Management

Currently, there is no cure for Giant Axonal Neuropathy. Management focuses on symptomatic treatment and supportive care, including:

• Physical Therapy: To maintain mobility and muscle strength.
• Occupational Therapy: To assist with daily activities.
• Orthopedic Devices: Such as braces to support weakened limbs.

Research and Future Directions

Research is ongoing to better understand the pathogenesis of GAN and to develop potential therapies. Gene therapy and other molecular approaches are being explored as possible treatments.

See Also

• Peripheral Neuropathy
• Neurodegenerative Disorders

External Links

• National Organization for Rare Disorders
• Genetic and Rare Diseases Information Center

NIH genetic and rare disease info

• NIH info on Neuropathy, giant axonal

Neuropathy, giant axonal is a rare disease.