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

Background -Leukodystrophies, a heterogeneous group of brain and spinal cord disorders, often pose challenges in establishingmolecular etiology. Vanishing White Matter Disease (VWMD) is a rare subtype of leukodystrophies presenting with characteristic clinical and MRI features, nevertheless, achieving diagnostic 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 sequences, within which hypointense regions appeared 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.