Alexander disease

Symptoms observed include delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia. Symptoms vary greatly between patients. Classification Traditionally, Alexander disease has been classified by age at onset and is divided into infantile, juvenile, and adult forms. In line with this method of classification, some researchers have proposed adding an additional neonatal division for cases where the disease began before birth. These divisions have the following characteristics: Other researchers have adopted a classification system with two divisions, Type I and Type II. The divisions have the following major characteristics: ==Cause==

Alexander disease is a genetic disorder primarily affecting the midbrain and cerebellum of the central nervous system. 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% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations. == Pathology ==

Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long-chain fatty acids in the brain, which destroy the myelin sheath. The cause of Alexander disease is a gain-of-function mutation in the gene encoding GFAP. The mutation causes protein aggregates called Rosenthal fibers to form in astrocytes' cytoplasm, but the exact method of this formation mechanism is not well understood. but occur in specific diseases, like some forms of cancer, Alzheimer's, Parkinson's, Huntington's, and ALS. The Rosenthal fibers found in Alexander disease do not share the distribution or concentration of other diseases and disorders. A CT scan of a patient with Alexander disease typically shows: • Decreased density of white matter • Frontal lobe predominance • Dilated lateral ventricles may present An MRI scan of a patient with Alexander disease typically shows: • Periventricular white matter change • Medullar atrophy • Signal change in the spinal cord == Diagnosis ==

Detecting the signs of Alexander disease is possible with magnetic resonance imaging (MRI), 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 MRI. 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. However, due to the similarity of symptoms to other diseases such as multiple sclerosis, many adults experience misdiagnosis until they receive an MRI scan confirming Alexander disease pathology. ==Treatment==

There is no known cure for Alexander disease. A bone marrow transplant has been attempted on a child, but it made no improvement. ==Prognosis==

The prognosis is generally poor. Individuals with the infantile form usually die before the age of seven. The average duration of the infantile form is usually about three years. Duration of the juvenile form is about six years. Usually, the later the disease occurs, the slower its course. ==Prevalence==

Its occurrence is very rare, with an estimated 1 in 2.7 million prevalence. More Type I cases have been reported than Type II cases, but researchers believe this may be due to high rates of misdiagnosis in adults. ==See also==