Alexander, disease ... (Alexander disease) - Gen GFAP
Alexander's disease is a rare disorder of the nervous system. It is one of a group of diseases called leukodystrophies, involving the destruction of myelin which insulates nerve fibers and promotes rapid transmission of nerve impulses. If myelin is not maintained properly, the transmission of nerve impulses can be interrupted.
Most cases of Alexander disease begin before age 2, and are known as the infantile form of the disease. Signs and symptoms of infantile form typically include macrocephaly, seizures, spasticity, mental retardation and developmental delay. Less commonly, the disease may manifest later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include dysarthria, dysphagia, seizures and ataxia. Rarely, Alexander's disease manifests itself in the first month of life (neonatal form), and is associated with intellectual disability, developmental delay, hydrocephalus and seizures. This disease is also characterized by deposits of abnormal proteins called Rosenthal fibers, appearing in astroglial cells, which are responsible for protecting and nourishing other cells in the central nervous system.
This disease is due to mutations in the GFAP gene, located on the long arm of chromosome 17 (17q21). This gene encodes the glial fibrillary acidic protein, which belongs to the family of intermediate filament protein. Intermediate filaments are networks that provide support to the cells. Several molecules of glial fibrillary acidic protein are joined to form the type of intermediate filament found in astroglial cells. These cells nourish and support the brain cells and spinal cord. If brain cells or spinal cord injuries or suffer damage from disease, astroglial cells react rapidly producing more glial fibrillary acidic protein.
Although their function is not completely understood, the glial fibrillary acidic protein is probably involved in the control of the shape, motion and function of astroglial cells. It is believed that astroglial cells play an important role in the functioning of other cells, including oligodendrocytes, which are involved in the production and maintenance of myelin. Furthermore, astroglial cells can help in maintaining the protective barrier that allows only certain substances can pass from the blood vessels to the brain.
There are more than 50 mutations in the GFAP gene in individuals with Alexander disease. Most of these mutations change one amino acid to glial fibrillary acidic protein. Other mutations, two amino acids added or deleted in the protein. All these changes alter the structure of the glial fibrillary acidic protein. Altered protein probably affects the formation of normal intermediate filaments. Consequently, glial fibrillary acidic protein abnormal can accumulate in astroglial cells, contributing to the formation of Rosenthal fibers, which alter cellular function. However, it is unclear how altered astroglial cells contributes to abnormal maintenance of myelin, leading to the signs and symptoms of disease Alexander.
This disease is inherited as an autosomal dominant, which means that a single copy of the gene altered is sufficient to express the process. Most cases are due to new mutations in the gene and occur in people with no family history of the disease. In rare cases, there is involvement in one parent.
Tests in IVAMI: in IVAMI perform detection of mutations associated with disease Alexander, by complete PCR amplification of the exons of the GFAP gene, 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).