Leukoencephalopathy evanescent (Leukoencephalopathy With vanishing white matter) white substance - Genes EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5.
Leukoencephalopathy with vanishing white matter is a progressive disease that affects the central nervous system. This disease causes deterioration of the white matter of the central nervous system, consisting of nerve fibers covered by myelin. In most cases, affected individuals show no signs or symptoms of the disease at birth. Affected children may present a slight delay in the development of motor skills such as crawling or walking. Throughout early childhood, those most affected engines begin to develop symptoms including spasticity and ataxia. There may also be some deterioration of mental function. Some affected women may have ovarian dysgenesis. Specific changes in the brain as seen by MRI (MRI) are characteristic of leukoencephalopathy with vanishing white matter, and may be visible before the appearance of symptoms.
While childhood onset is the most common form of the disease, some severe forms are evident at birth. A severe form, called early onset Cree leukoencephalopathy. Milder forms may not be apparent until adolescence or adulthood, when behavioral or psychiatric problems may be early signs of the disease. Some women with milder forms that survive adolescence have ovarian dysfunction. In general, the progression of the disease is irregular, with periods of relative stability interrupted by episodes of rapid decline.
This disease is due to mutations in the genes EIF2B1, located on the long arm of chromosome 12 (12q24.31), EIF2B2, located on the long arm of chromosome 14 (14q24.3), EIF2B3, located on the short arm of chromosome 1 (1p34.1), EIF2B4, located on the short arm of chromosome 2 (2p23.3) and EIF2B5, located on the long arm of chromosome 3 (3q27.1). These genes, encoding subunits (alpha subunit, subunit beta, gamma subunit, epsilon subunit delta subunit) of a protein called eIF2B. The eIF2B protein helps regulate the synthesis in the cell by interacting with another protein, eIF2. The eIF2 protein is called initiation factor as it is involved in the initiation of protein synthesis. Proper regulation of protein synthesis is vital to ensure that appropriate for the cell to cope with the changing conditions are available concentrations.
Mutations have been identified in EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes in people with leukoencephalopathy with vanishing white matter. Mutations in the gene EIF2B5 represent about 65% of all cases of the disease. These mutations cause partial loss of function of the protein eIF2B several ways. For example, they may affect the ability of the subunits of the protein to form a complex with the other, or make it more difficult for the protein inserted into the initiation factor. The partial loss of function eIF2B makes it harder for cells to regulate body protein synthesis and cope with changing conditions and stress. It is believed that the cells of the white matter can be particularly affected by abnormal stress response, leading to the signs and symptoms of leukoencephalopathy with vanishing white matter.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with leukoencephalopathy with vanishing white matter, by complete PCR amplification of the exons of EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).