Vanishing White Matter: the Next 10 Years

Abstract

Vanishing white matter (VWM) is an inherited and often severe brain disease. It is caused by mutations in the genes for eIF2B, a protein that plays a key role in mRNA translation. The age of onset and clinical features are highly variable. In severe cases, onset may be antenatal and other organs are affected. The main feature is always a progressive encephalopathy, faster deterioration being provoked by head injury or febrile infections. The myelinating cells, oligodendrocytes, are affected in VWM. Initial studies suggested that VWM mutations decreased eIF2B’s activity. However, recent findings indicate that the situation is more complex. Studies in human brain samples or a mouse model for VWM indicate that development of astroglial cells and oligodendrocytes is impaired. Defects in eIF2B likely affect cell stress pathways and the expression of specific proteins, although their identities remain unknown.