Background and objectives: Vanishing white matter disease (VWMD) is an autosomal recessive leukoencephalopathy caused by mutations in the EIF2B1-5 genes, typically rare in adulthood. We present a case of adult-onset VWMD with a novel EIF2B2 mutation.
Methods: We collected the patient's clinical data, cerebrospinal fluid (CSF) results, laboratory tests, imaging features, genetic analysis, and follow-up data over a 4-year period.
Results: A 40-year-old male patient presented with difficulty walking and leg pain. Neurological examination revealed acalculia, slow reaction times, and ataxia. Magnetic resonance imaging (MRI) scans showed diffuse, symmetric lesions with cerebrospinal fluid-like signals predominantly in the subcortical, periventricular, and cerebellar white matter. Genetic testing identified a compound heterozygous mutation in EIF2B2, consisting of a novel nonsense mutation (c.378 T > G, p.Tyr126*) and a reported missense mutation (c.818A > G, p.Lys273Arg) (NM_014239.4).
Discussions: This report highlights the diverse phenotypic manifestations of VWMD and underscores the importance of considering EIF2B2 mutations in adult male patients with bilaterally symmetric hyperintensities in white matter and slowly progressive symptoms.
Keywords: Adult onset; Compound heterozygous mutations; EIF2B2; Vanishing white matter disease.
© 2025. Fondazione Società Italiana di Neurologia.