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Brain of a 4-year-old boy with Alexander disease showing macroencephaly and periventricular demyelinisation (note brownish discoloration around the cerebral ventricles)
|Classification and external resources|
|OMIM||203450 137780 137780 203450|
Alexander disease, also known as fibrinoid leukodystrophy, 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.
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, such that the child of a parent with the disease has a 50/50 chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.
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. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer. The Rosenthal fibers found in Alexander disease are not distributed in the same areas or as concentrated when compared to other diseases and disorders.
Delays in development of some physical, psychological and behavioral skills, progressive enlargement of the head (macrocephaly), seizures, spasticity, in some cases also hydrocephalus, idiopathic intracranial hypertension (IIH), dementia.
Alexander disease causes the affected person to slowly begin to lose body function and eventually the ability to talk. It also causes an overload of long chain fatty acids that the body cannot dispose of. This overload of fatty acids builds up in the brain and destroys the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein.
It is possible to detect the signs of Alexander disease with Magnetic Resonance Imaging, which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MR imaging. Alexander disease may also be revealed by genetic testing for the known cause of Alexander disease. A rough diagnosis may also be made through revealing of clinical symptoms including, enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.
Occurrence and prevalence
Its occurrence is very rare. The infantile form from birth to 2 years of age. The average duration of the infantile form of the illness is usually about 3 years. Onset of the juvenile form presents between two and twelve years of age. Duration of this form is in most cases about 6 years. The Adult form from twelve years and older. 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 500 reported cases.
- "MUTATION KEY TO ALEXANDER DISEASE" - United Press International
- GeneReviews/NCBI/NIH/UW entry on Alexander disease
- alexander_disease at NINDS
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