Early MR imaging and spectroscopy appearance of eIF2B-related leukoencephalopathy

Leukoencephalopathy with vanishing white matter (VWM) (OMIM 603896) is a progressive disease with autosomal recessive inheritance, linked to mutations in either of the five genes encoding the subunits of the eukaryotic translation initiation factor eIF2B.^1,2 Before molecular genetic testing was available, the diagnosis of VWM could be suspected on the basis of MRI and proton MR spectroscopy (¹H-MRS) findings, which characteristically show diffuse signal abnormality of the cerebral white matter with evidence of rarefaction and cystic degeneration.^3,4 Here we report a patient with a childhood onset of ataxia and on MRI a diffuse leukoencephalopathy without rarefaction. Appearance of cysts within the affected white matter 15 years after onset prompted molecular genetic testing, which confirmed the diagnosis of VWM.

The patient's developmental milestones were normal. At age 9 years his gait was unstable and wide-based with frequent falls and he showed an intention tremor. MRI showed symmetric diffuse hyperintensity of the cerebral white matter on proton density images (figure). Laboratory workup for X-linked adrenoleukodystrophy, metachromatic leukodystrophy, mitochondrial dysfunction, and spinocerebellar ataxia types 1, 2, 3, and 6 was negative. At age 11 …