TY - CHAP M1 - Book, Section TI - Vanishing White Matter A1 - van der Knaap, Marjo S. A1 - Bugiani, Marianna A1 - Boor, Ilja A1 - Proud, Chris G. A1 - Scheper, Gert C. A2 - Valle, David L. A2 - Antonarakis, Stylianos A2 - Ballabio, Andrea A2 - Beaudet, Arthur L. A2 - Mitchell, Grant A. PY - 2019 T2 - The Online Metabolic and Molecular Bases of Inherited Disease AB - “Vanishing white matter” (VWM) is an autosomal recessively inherited disorder in which the basic defect resides in eukaryotic initiation factor 2B (eIF2B). The clinical onset and severity of VWM vary greatly. The classical form has an early-childhood onset, but onset can vary from antenatal and early-infantile onset at one end of the spectrum to late-adult onset at the other end. Age of onset is predictive of disease severity. The clinical and histopathologic manifestations of VWM are dominated by degeneration of the white matter of the central nervous system. Organs other than the brain are rarely affected, with the exception of the ovaries. In addition to a chronic progressive encephalopathy, there are typically episodes of rapid and major deterioration, provoked by stresses like febrile infections of minor head trauma. VWM is caused by mutations in any of the five genes EIF2B1-5, encoding the α-ϵ subunits of eIF2B. The reason for the selective vulnerability of the white matter of the central nervous system and, less consistently, the ovaries is poorly understood. Multiple hypotheses have been put forward, including the effects of inappropriate activation of the unfolded protein response in oligodendrocytes and astrocytes, differing cellular levels of eIF2B or eIF2/eIF2B ratios and aberrant control of translation of specific mRNAs. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/10/13 UR - ommbid.mhmedical.com/content.aspx?aid=1181480196 ER -