A Novel Mutation in the EIF2B4 Gene Associated with Leukoencephalopathy with Vanishing White Matter

Abstract EN

Leukoencephalopathy with vanishing white matter (VWM; MIM #603896) is an autosomal recessive disorder, characterized by childhood ataxia, spasticity, and variable optic atrophy.

The course is chronic progressive with episodes of rapid deterioration, provoked by febrile illnesses, minor head trauma, or acute fright, with most patients succumbing to illness within few years of onset.

Three forms of VWM has been described based on disease onset, which ranges from a subacute infantile form (onset age <1 year), an early childhood form (onset age 1–5 years), and a late-childhood/juvenile form (onset age 5–15 years) [1–3].

The diagnosis is based on clinical findings, characteristic MRI features indicative of vanishing of the cerebral white matter, and an identifiable pathogenic variant in one of the genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), which is essential in all cells of the body for the initiation of translation of RNA into protein during protein synthesis and its regulation under different stress conditions such as fever [4, 5].

Its effect is predominantly seen on oligodendrocytes and astrocytes while there is sparing of other cell types [2].