An autopsy case of infantile-onset vanishing white matter disease related to an EIF2B2 mutation (V85E) in a hemizygous region.

We report a rare autopsy case of early infantile-onset vanishing white matter disease, with a submicroscopic deletion of 14q24.3, which included EIF2B2 and a missense mutation of EIF2B2 (V85E) of the remaining allele. The patient was a 4-year-old boy, who was found to have suddenly died during sleep. Physical and mental development began to deteriorate after convulsions at 10 month of age, and did not recover to baseline measurements. At autopsy, the brain showed a marked decrease in volume of white matter, with no typical cystic rarefaction. Histopathologically, the affected white matter showed diffuse loss of myelin fibers, meager astrogliosis with dysmorphic astrocytes, and loss of oligodendrocytes. Proliferative and apoptotic markers were negative for oligodendrocytes in the severely affected area. These findings may be related to the severity of the disease, and might be a feature of the EIF2B2 mutation pattern of the patient. Additionally, unusual fatty infiltration of both ventricles of the heart was found. These findings were suspected as early pathology of arrhythmogenic right ventricular cardiomyopathy due to characteristic gene mutation in the present case. In the present case, the defect EIF2B2 caused by hemizygosity may be related to early onset of the disease and the unusual pathological changes with vulnerability of oligodendrocytes and astrocytes, as well as cardiac abnormalities and sudden unexpected death.