Atypical presentation of Wolcott-Rallison syndrome with severe Epstein-Barr virus hepatitis, secondary peroxisomal...

A female toddler born to consanguineous parents presented with severe Epstein-Barr virus hepatitis, hyperferritinaemia and severe neutropenia, initially suggesting haemophagocytic lymphohistiocytosis. Metabolic screening revealed elevated very-long-chain fatty acids and dicarboxylic aciduria, mimicking a peroxisomal disorder. Brain MRI demonstrated cortical thickening and smoothing that were more pronounced in both temporal lobes, with poorly formed gyri characteristic of pachygyria-lissencephaly, underlying subcortical white matter thinning affecting the temporo-insular parenchyma and moderate cerebellar hypoplasia. Exome sequencing identified a homozygous pathogenic EIF2AK3 mutation (c.3193C>T, p.Arg1065*), confirming Wolcott-Rallison syndrome. This case expands the Wolcott-Rallison syndrome phenotype: neonatal diabetes and skeletal dysplasia were absent at presentation, and the neuroimaging demonstrated previously unreported patterns. It highlights that severe viral infections can create misleading biochemical patterns in patients with endoplasmic reticulum stress-pathway defects, emphasising the importance of comprehensive genetic testing.