What is Giant Axonal Neuropathy?

GAN is primarily a neurological disorder that presents in early childhood. It is marked by progressive nerve dysfunction due to the accumulation of abnormally large axonal swellings filled with disorganized neurofilaments. This axonal damage leads to a range of symptoms that affect the motor and sensory pathways of the nervous system.

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Causes of Giant Axonal Neuropathy

The root cause of GAN is genetic mutations in the GAN gene, which encodes the gigatons protein. This protein is essential for maintaining the normal structure and function of the nerve axons. GAN is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent. When both parents carry one copy of the mutated gene, there is a 25% chance that the child will be affected by GAN during each pregnancy.

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Symptoms of Giant Axonal Neuropathy

The symptoms of GAN typically manifest in early childhood, usually between the ages of 3 and 5, and progressively worsen over time. The most common symptoms include:

Additional Symptoms

In some cases, individuals with GAN may also experience seizures, scoliosis, and intellectual disabilities. The severity and combination of symptoms can vary significantly from person to person.

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Diagnosis of Giant Axonal Neuropathy

Diagnosing GAN involves a combination of clinical evaluation, family history analysis, and several diagnostic tests:

Neurological Examination

A thorough neurological examination is essential to assess muscle strength, reflexes, coordination, and sensory function. Noticing the characteristic tightly curled hair can also serve as an early indicator of GAN.

Genetic Testing

Genetic testing, which identifies mutations in the GAN gene, confirms the diagnosis. This testing is crucial for distinguishing GAN from other similar neuropathic disorders.

Nerve Biopsy

A nerve biopsy may be conducted to observe the characteristic giant axons under a microscope. This procedure involves taking a small sample of nerve tissue, typically from the sural nerve in the leg.

Electromyography (EMG) and Nerve Conduction Studies

These tests measure the electrical activity of muscles and the speed of conduction of electrical impulses through nerves, respectively. Abnormal results may indicate neuropathy.

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Treatment and Management of Giant Axonal Neuropathy

Currently, there is no cure for GAN, and treatment focuses on managing symptoms and improving quality of life. A multidisciplinary approach involving various healthcare professionals is often recommended.

Physical and Occupational Therapy

Regular physical therapy can help maintain muscle strength and flexibility, while occupational therapy can assist with daily activities and improve fine motor skills.

Orthopaedic Interventions

Braces or orthopaedic devices may be necessary to support weak muscles and improve mobility. In some cases, surgery might be required to correct skeletal deformities such as scoliosis.

Medications

While there is no specific medication to treat GAN, medications may be prescribed to manage symptoms such as muscle spasms, seizures, or pain.

Genetic Counseling

Given the hereditary nature of GAN, genetic counselling is recommended for affected individuals and their families. It provides insight into the risks of recurrence in future pregnancies and informs family planning decisions.