Alexander Disease (ALX)
Leukodystrophy with Rosenthal Fibers
Megalencephaly with Hyaline Inclusion
Megalencephaly with Hyaline Panneuropathy
Alexander Disease is one of a group of neurological conditions called Leukodystrophies. These are disorders that cause abnormalities and the destruction of myelin, the “white matter” that protects nerve fibers in the brain. Myelin is essentially made up of water proteins and mostly lipids, it covers the axons of all neurons in the form of a myelin sheath as it helps insulate the nerve fibers and promotes rapid transmission of nerve impulses. Myelin is produced by two different types of Glial cells, Oligodendrocytes produce myelin in the central nervous system (Brain and Spine) and Schwann cells produce myelin in the peripheral nervous system (Outside Brain and Spine). If myelin is not properly maintained, the transmission of nerve impulses could be disrupted and as myelin deteriorates nervous system functions can be impaired. Alexander disease targets the CNS.
ALX is caused by a mutation in the GFAP (Glial fibrillary acidic protein) gene on chromosome 17. Molecules of this protein bind together to form intermediate filaments which are used to support and strengthen cells. The mutation causes a structural alteration in GFAP which impairs the formation of normal intermediate filaments and they collect in cells called astrocytes. Astrocytes are non-neuronal glial cells that provide biochemical support to endothelial cells that form the blood-brain barrier, provide nutrients for nervous tissue and maintenance of extracellular ion balance etc. This leads to the formation of Rosenthal fibers in the astrocytes, abnormal clumps of GFAP. Therefore no nutrients are provided to the oligodendrocytes and as a result myelin is slowly degenerated.
Most cases of ALX begin before 2 years...
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