ClinVar

In 4 patients from 2 unrelated families with early-onset leukoencephalopathy with vanishing white matter (VWM5; 620315), Passemard et al. (2007) identified compound heterozygosity for mutations in the EIF2B5 gene. In a brother and sister, they identified a 944G-A transition resulting in an arg315-to-his (R315H) substitution and a 166T-G transversion resulting in a phe56-to-val (F56V; 603945.0010) substitution. In 2 sisters, they identified the R315H mutation and a 167T-G transversion resulting in a phe56-to-cys (F56C; 603945.0011) substitution. In the first family, the 2 sibs had acute neurologic deterioration in infancy following viral infections. Brain MRIs showed severe white matter abnormalities and complete disappearance of hemispheric white matter, respectively. Both developed progressive severe macrocephaly after age 3 years. In the second family, 1 sister who survived beyond age 3 years developed macrocephaly. Passemard et al. (2007) suggested that altered brain water balance may result in swelling of the disease white matter and macrocephaly in some patients with VWM disease.