Leukoencephalopathy with vanishing white matter

Leukoencephalopathy with vanishing white matter is a genetic condition caused by mutations in any of 5 genes - EIF2B1 , EIF2B2 , EIF2B3 , EIF2B4 , and EIF2B5. These genes give the body instructions to make the five parts (subunits) of a protein called eIF2B. This protein helps regulate overall production of protein in cells (protein synthesis). Proper regulation of protein synthesis ensures that the correct levels of protein are available for cells to cope with changing conditions and stress.

Mutations in any of these 5 genes results in partial loss of eIF2B function, making it more difficult for cells to regulate protein synthesis and deal with changing conditions and stress. Researchers believe that cells in the white matter may be particularly affected by an abnormal response to stress, thus causing the signs and symptoms of this condition.

Approximately 90% of affected people have been found to have mutations in one of these 5 genes. Approximately 10% of families who have been diagnosed by MRI and clinical features do not have an identifiable mutation, suggesting that additional genes may also be responsible for the condition.

Leukoencephalopathy with vanishing white matter is inherited in an autosomal recessive manner. This means that a person must have a mutation in both copies of the responsible gene to be affected. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not have signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Leukoencephalopathy with vanishing white matter is a genetic condition caused by mutations in genes involved in the regulation of the production of protein; it is inherited in an autosomal recessive manner. There are cases in which an affected person does not appear to have an identifiable mutation in one of the 5 genes known to be responsible for the condition (approximately 10% of affected people). However, these cases are thought to be due to additional, responsible genes that have not yet been identified.

To our knowledge, there is no evidence that suggests or states that there is any association between maternal carbon disulfide exposure and leukoencephalopathy with vanishing white matter in a child. Long-term exposure to carbon disulfide may contribute to the development of various other neurologic effects in an exposed person. Reproductive effects that have been observed in people exposed to carbon disulfide by inhalation include decreased sperm count and menstrual disturbances. In experimental animal studies, carbon disulfide has been shown to increase malformations, but at dose levels much higher than those anticipated in humans.

Treatment for leukoencephalopathy with vanishing white matter is supportive, aiming to alleviate symptoms. Management may include physical therapy and rehabilitation for motor dysfunction (mainly spasticity and ataxia); and anti- seizure medications for seizures.

Infections and fevers should be prevented when possible through the use of vaccinations; low-dose maintenance antibiotics during winter months; antibiotics for minor infections; and antipyretics (fever-reducing medications) for fever. For children, wearing a helmet outside can help minimize the effects of head trauma. Contact sports, head trauma, and stressful situations (including high body temperature) should be avoided.

More detailed information about the management of leukoencephalopathy with vanishing white matter is available on the GeneReviews Web site.