Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 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 2 and 13 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. 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 disease occurs in both males and females, and no ethnic, racial, geographic or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease. Presentation
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. Cause
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.
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. Treatment
No cure or standard procedure for treatment is known, although a University of Wisconsin study shows promise with gene editing of the astrocytes. A phase III clinical trial of an antisense therapy, sponsored by Ionis Pharmaceuticals, began in 2021. 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. Prognosis
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 seven. Usually, the later the disease occurs, the slower its course. Prevalence
Its occurrence is very rare. The infantile form occurs from birth to 2 years of age. The average duration of the infantile form is usually about 3 years. Onset of the juvenile form presents between 2 and 12 years of age. Duration of this form is in most cases about 6 years. The adult form occurs after 12 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. No more than 500 cases have been reported.