Alexander disease
Alexander disease is a rare, progressive disorder of the nervous system that involves the destruction of myelin and the formation of abnormal protein deposits called Rosenthal fibers.
Overview
Alexander disease is a rare disorder of the nervous system and is part of a group of conditions called leukodystrophies. These disorders involve the destruction of myelin, the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. As myelin deteriorates, nervous system functions are impaired.
Symptoms
The disease is categorized by the age of onset:
- Infantile form: Most cases begin before age 2. Symptoms include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay.
- Juvenile and adult forms: Onset occurs later in childhood or in adulthood. Common problems include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia).
- Neonatal form: Rarely occurs within the first month of life, associated with severe intellectual disability, developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.
The disease is also characterized by abnormal protein deposits known as Rosenthal fibers, which are found in specialized cells called astroglial cells.
Causes
Mutations in the GFAP gene cause Alexander disease. This gene provides instructions for making glial fibrillary acidic protein. Mutations lead to the production of a structurally altered protein that impairs the formation of normal intermediate filaments, causing the accumulation of Rosenthal fibers, which impair cell function.
Inheritance
This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new (de novo) mutations in the gene in people with no family history of the disorder.