Genetics of Alexander Disease: A Detailed Guide
Alexander disease is classified as a leukodystrophy, a type of disorder in which the myelin has abnormalities. This disorder is progressive and is usually fatal. Those diagnosed with the infantile form typically will not live more than six years. Those with the adult and juvenile-onset forms often experience a lengthy, slower course.
Through understanding the genetics of Alexander disease, we know that nervous system function is impaired. The exact incidence rate is not known. However, since the disorder was first talked about in 1949, there have been about 500 reported cases.
Genetics
By knowing about the genetics of Alexander disease, we know that GFAP gene mutations are the cause of this disorder. This gene is responsible for giving the instructions necessary for making the glial fibrillary acidic protein. This protein is necessary for cell strength. Overall, mutations will result in impaired cell function. This disorder is inherited in an autosomal dominant pattern.
Signs and Symptoms
The infantile form may cause spastic quadriparesis and mental retardation. Infants may require feeding assistance because feeding may become difficult. They often have an enlarged head circumference, and increased intracranial pressure due to hydrocephalus. Other possible signs and symptoms may include megalencephaly, failure to thrive, seizures, and progressive psychomotor retardation.
The juvenile form is characterized by the inability to cough and difficulty swallowing and talking. The extremities, especially the legs, may be spastic and weak. Other possible signs and symptoms may include vomiting, kyophoscoliosis, slow decline in mental function, spasticity, and ataxia.
The adult form of this disorder is the most rare, and in most cases, the most mild. Impaired coordination, speech articulation difficulty, sleep disturbances, and swallowing difficulties may occur.
Diagnosis
A blood sample is usually obtained so that genetic testing can be done. Most patients are able to have the genetic testing done. Certain clinical symptoms, such as the enlarged size of the head, in combination with negative tests for other leukodystrophies and radiological studies can make a suggestive diagnosis. If MRIs are done, there is often a characteristic pattern.
Treatment
No cure exists for this genetic disorder. Treatment focuses on alleviating the patient’s symptoms. If the patient has water on their brain, known as hydrocephaly, surgery may be necessary. During the surgery, a shunt is inserted so that some of the fluid can be drained away to help relieve the pressure. On one child, a bone marrow transplant was done, but the child did not improve. Symptoms like seizures, sleep disturbances, and spasticity may be helped by certain medications. Physical, occupational, and speech therapy may also benefit some patients.
Resources
Cleveland Clinic. (2010). Alexander Disease. Retrieved on December 29, 2010 from the Cleveland Clinic: https://my.clevelandclinic.org/disorders/alexander_disease/hic_alexander_disease.aspx
Genetics Home Reference. (2008). Alexander Disease. Retrieved on December 29, 2010 from Genetics Home Reference: https://ghr.nlm.nih.gov/condition/alexander-disease
