Alexander disease.

Alexander disease is a rare and generally fatal disorder of the central nervous system, originally defined by the distinctive neuropathology consisting of abundant Rosenthal fibers within the cytoplasm and processes of astrocytes. More recently, mutations in GFAP, encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes, have been identified in nearly all patients. No other genetic causes have yet been identified. The precise mechanisms by which mutations lead to disease are poorly understood. Despite the genetic homogeneity, there are a wide range of clinical phenotypes. The genetic issues and the approach to diagnosis are the prime consideration in this chapter.