Alexander disease

Alexander disease is a rare disorder of the nervous system. It is considered one of the leukodystrophies, a group of disorders in which the primary abnormality is the inability to maintain myelin. Myelin is a whitish substance that wraps around certain nerve cells and ensures the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses is disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.

Most cases of Alexander disease begin before age 2 years (the infantile form). Signs and symptoms of the infantile form typically include an enlarged brain and head (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), mental retardation, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination (ataxia).

Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers, which are found in specialized brain cells called astroglial cells. Astroglial cells support and nourish nerve cells in the brain and spinal cord.

The prevalence of Alexander disease is unknown. About 500 cases have been reported since the disorder was first described in 1949.

Mutations in the GFAP gene cause Alexander disease.

The GFAP gene provides instructions for making a protein called glial fibrillary acidic protein. Several molecules of this protein bind together to form intermediate filaments. Intermediate filaments are important for the normal activities of astroglial cells. Mutations in the GFAP gene alter the structure of glial fibrillary acidic protein. The altered protein probably disturbs the formation of normal intermediate filaments. As a result, glial fibrillary acidic protein may accumulate as a component of Rosenthal fibers and interfere with the normal activities of astroglial cells. It is not well understood how impaired astroglial cells contribute to the abnormal formation or maintenance of myelin.

Read more about the GFAP gene.

Alexander disease is considered an autosomal dominant disorder, which means one copy of the altered gene in each cell is sufficient to cause the disease. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In some rare adult cases, a GFAP mutation may be passed to children of an affected parent.