Alexander disease

Alexander disease is a slowly progressing and fatal neurodegenerative disease. It is a very rare disorder which results from a genetic mutation and mostly affects infants and children, causing developmental delay and changes in physical characteristics.

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Clinical features

Delays in development of some physical, psychological and behavioral skills, progressive enlargement of the head (macrocephaly), seizures, spasticity, in some cases also hydrocephalus, dementia, clumsy movements.

Pathology

  Alexander disease is a genetic disorder affecting the central nervous system (midbrain and cerebellum). It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP) that maps to chromosome 17q21. It is inherited in an autosomal dominant manner.

Alexander disease belongs to leukodystrophies, a group of diseases which affect growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers.

CT shows:

• decreased density of white matter
• frontal lobe predominance
• +/- dilated lateral ventricles

Cause

The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein.

Occurrence and prevalence

Very rare. The infantile form (80% of all cases) starts usually at the age of six months or within the first two years. The average duration of the infantile form of the illness is usually about 3 years. Onset of the juvenile form (14% of all cases) presents usually between four to ten years of age. Duration of this form is in most cases about 8 years. In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis.

There are no more than 300 cases reported.

Treatment

Prognosis

The prognosis is generally poor. With early onset, death usually occurs within 10 years after the onset of symptoms. Usually, the later the disease occurs, the slower its course is.

See also

• The Myelin Project
• The Stennis Foundation
• Glial fibrillary acidic protein