Chapter 19 - Vanishing white matter disease

Abstract

Childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) disease is an autosomal recessive disorder characterized by progressive ataxia, spasticity, and, rarely, optic atrophy. Clinical disease onset can occur at any age, but most commonly in early childhood (age 1–5 years). Motor and intellectual development are normal or mildly delayed, followed by motor deterioration with a chronic progressive or subacute course. Chronic progressive decline may be exacerbated by rapid deterioration during any type of physical or psychological stress. Behavioral or psychiatric abnormalities are common in the adult-onset form. CACH/VWM is suspected typically when clinical findings are combined with characteristic abnormalities on brain MRI. The diagnosis can be confirmed in 90% of the patients by the identification of mutations in one of five genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5) that encode the subunits of the eukaryotic translation initiation factor 2B (eIF2B). Research is focused on mitigating the hypersensitivity of glial cells to cellular stress as an approach to therapy of this devastating disease.