Vanishing White Matter Disease in Children: An Unusual Association, a Novel Mutation, and a Literature Review
Zahra Alsahlawi1,2, Hasan M Isa1,2, Sulaiman Alresias2
1Department of Pediatrics, Arabian Gulf University, Manama, BHR.
Abstract:
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.
Insights
Vanishing white matter (VWM) disease, a rare leukodystrophy, accounts for 9.5% of cases in Bahrain. Triggers include infections and vaccinations, leading to rapid neurological decline and poor outcomes.
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Vanishing white matter (VWM) disease is an autosomal recessive leukodystrophy caused by mutations in the eukaryotic initiation factor 2B (EIF2B) gene.
- While rare globally (0.001%), VWM is among the most common leukodystrophies, yet its worldwide incidence and prevalence remain unclear.
Observation:
- In Bahrain, VWM disease was identified in 9.5% of 21 diagnosed leukodystrophy patients.
- Triggers for VWM manifestation included vaccinations and infections, leading to rapid neurological deterioration, loss of milestones, and seizures.
- Magnetic resonance imaging (MRI) revealed characteristic demyelination and leukodystrophy changes.
Findings:
- One patient presented with ulcerative colitis, a previously unreported association.
- Genetic analysis in one patient identified a novel homozygous missense mutation in the EIF2B3 gene (c.25G>A, p.Ala9Thr).
- Outcomes were poor, with one patient progressing to a vegetative state and the other succumbing to the disease.
Implications:
- This study details VWM disease prevalence, clinical characteristics, and outcomes in Bahrain, contributing to understanding this rare condition.
- Findings highlight the need for increased awareness and diagnostic efforts for VWM disease, particularly in regions with unclear epidemiological data.
- The identification of a novel mutation and an unusual comorbidity (ulcerative colitis) expands the known spectrum of VWM disease presentation and genetics.
