WED 203 Vanishing white matter disease due to variant mutations in the EIF2B- 1 gene

Abstract

This otherwise fit and well 25 year old gentleman presented with new onset intermittent stabbing headaches associated with generalised tiredness and one nocturnal seizure. His neurological examination was normal and there were no dysmorphic features. He continues to remain intact neurologically.Initial CT Brain showed periventricular low attenuation changes bilaterally associated with bi-frontal atrophy. MRI Brain confirmed extensive periventricular White Matter T2 high signal changes in keeping with Leukomalacia and generalised cerebral atrophy.Genetic testing revealed 2 variant mutations in the EIF2B1 gene, of which one has been previously reported pathogenic and the other is a frame shift variant – likely pathogenic consistent with a diagnosis of vanishing White Matter Leukodystrophy.VWM leukodystrophy is an autosomal recessive disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with WM lesions on brain imaging. The prevalence is unknown; and age at onset can range from early infancy to adulthood. Rapid neurological deterioration can occur following minor head trauma, infections and stress. Mutations in EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes cause leukoencephalopathy with Vanishing White Matter.