Vanishing white matter disease, a rare leukodystrophy with mutation in the EIF2B5 gene

Background - Leukodystrophies, a hete roge neous group of brain and spinal cord dis orders, often pose challenges in es tab li shing molecular etiology. Vanishing White Matter Disease (VWMD) is a rare sub type of leu kodys trophies presenting with characteristic clinical and MRI features, ne ver theless, achieving diag nostic certainty requires genetic studies. Case presentation - Our patient is a nine year old girl, who developed progressive gait difficulties at around 3-4 years of age. Her brain MRI showed confluent lesions with increased signal intensity in the cerebral and cerebellar white matter on T2/FLAIR se quen ces, within which hypointense regions ap peared with signal intensity resembling that of the cerebrospinal fluid on T1 sequences. Whole exome sequencing identified a homozygous likely pathogenic variant within the EIF2B5 gene in the proband, which was present in a heterozygous state in both asymptomatic parents. Having the clinical and molecular genetic diagnosis established, we explored therapeutic possibilities for the patient. Conclusion - VWMD is a severe form of leukodystrophies with little or no disease modifying therapy available until recently. A better understanding of its molecular pathogenesis offers some hope for new inventive therapies.