Gigantic axonal neuropathy (GAN)
- Article
- 2021-03-10
Giant axonal neuropathy (GAN) is a rare inherited genetic disorder affecting both the central and peripheral nervous systems. Most children with GAN will start to show symptoms of the disease sometime before the age of five. Signs of GAN usually start in the peripheral nervous system, which controls movement and sensation in the arms, legs, and other parts of the body. The typical symptoms of GAN are clumsiness and muscle weakness that progress from a "waddling gait" to pronounced difficulty in walking. Additional symptoms include numbness or lack of sensation in the arms and legs, seizures, nystagmus (rapid back and forth movement of the eyes) and impaired cognitive development. A characteristic sign of the disease is dull, tightly curled hair that differs markedly from that of the parents in color and texture.
Researchers have discovered more than 20 different mutations associated with GAN in a gene, GAN1, which makes a protein called gigaxonin . These mutations disrupt the regulation or production of gigaxonin in the nervous system. As a result, axons, the long tails of neurons that allow them to communicate with other nerve cells, swell up with tangled filaments and become abnormally large. Ultimately, these axons deteriorate and cause problems with movement and sensation because neurons can no longer communicate with each other.
Doctors diagnose GAN by using a variety of tests, including one that measures nerve conduction velocity, a brain MRI, and a peripheral nerve biopsy (which involves removing a piece of tissue from a peripheral nerve and examining it to look for swollen axons). A definitive diagnosis using genetic testing is only available on the basis of research.
GAN is inherited in an autosomal recessive pattern, which means that both parents of a child with GAN must carry a copy of the mutated gene. Parents usually will not show any signs of the disease.
Therapy
Treatment is symptomatic. Children with GAN and their families usually work with a medical team consisting of a pediatric neurologist, orthopedic surgeon, physiotherapist, psychologist, and speech and occupational therapists. The main goals of treatment are to maximize intellectual and physical development and minimize their deterioration over time. Many children with GAN start with normal intellectual development and can follow a regular school program. Children should be monitored at least once a year to assess their intellectual abilities and to detect the presence of neurological deterioration.
Prognosis
GAN generally progresses slowly as neurons degenerate and die. Most children have problems walking in the early stages of the condition. Later, they may lose feeling, coordination, strength and reflexes in their arms and legs. Over time, the brain and spinal cord can become involved, causing a gradual decline in mental function, loss of control over body movements and seizures. Most children become wheelchair dependent in the second decade of their lives. Some children can survive into early adulthood.
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