Vanishing White Matter Disease in Children: An Unusual Association, a Novel Mutation, and a Literature Review.

Vanishing white matter (VWM) disease is an autosomal recessive disorder caused by mutations in the gene EIF2B encoding the subunits 1-5 of eukaryotic initiation factor 2B. Although rare, with a reported prevalence of 1:80,000 (0.001%), it was considered as one of the most common leukodystrophies. However, the worldwide incidence and prevalence of this disease are not clear. In Bahrain, of 21 patients who were diagnosed with leukodystrophy, two patients were found to have VWM disease accounting for 9.5%. Vaccinations and infections were the trigger factors for this disease to manifest. Rapid neurological deterioration, loss of developmental milestones, and seizure disorders are the main presentations in both patients. Magnetic resonance imaging (MRI) showed the classical radiological changes of demyelination and leukodystrophy. Patient 1 had associated ulcerative colitis, a finding that was not reported before. Patient 1's condition progressed to a vegetative stage, while patient 2 passed away, reflecting the poor disease outcome. In patient 2, a novel homozygous missense mutation was found in the EIF2B3 gene (c.25G>A, p.Ala9Thr). In this report, we present in detail the prevalence of VWM disease among cases with leukodystrophy, patients' characteristics, clinical presentations, radiological findings, associated diseases, genetic results, and clinical outcomes in the main tertiary hospital in Bahrain between 1998 and 2024. Moreover, we conducted a thorough literature review on this rare condition.