|Brain of a 4-year-old boy with Alexander disease showing macroencephaly and periventricular leukomalacia (note brownish discoloration around the cerebral ventricles)|
Alexander disease is one of a group of neurological conditions known as the leukodystrophies. Leukodystrophies are ailments caused by anomalies in the myelin, which protects nerve fibers in the brain. According to the National Institute of Neurological Disorders and Stroke, "the destruction of white matter is accompanied by the formation of Rosenthal fibers—abnormal clumps of protein that accumulate in astrocytes in the brain. The most common type of Alexander disease is the infantile form that usually begins during the first two years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The juvenile form of Alexander disease has an onset between the ages of two and thirteen years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. Alexander disease is a progressive and often fatal disease."
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.
Alexander disease is a genetic disorder 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.
Alexander disease belongs to leukodystrophies, a group of diseases that affect the 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 do not share the distribution or concentration of other diseases and disorders.
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 mutation in the gene encoding glial fibrillary acidic protein (GFAP).
A CT scan shows:
It is possible to detect the signs of Alexander disease 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. 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.
There is currently no cure or standard procedure for treatment. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.
The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of 7. Usually, the later the disease occurs, the slower its course is.
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.
- "Alexander Disease Information Page". National Institute of Neurological Disorders and Stroke. 2018. This article incorporates text from this source, which is in the public domain.
- GeneReviews/NCBI/NIH/UW entry on Alexander disease
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- alexander_disease at NINDS
- "Cause of brain disease found" -BBC News
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