Background: Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by early infancy onset diabetes mellitus and multiple epiphyseal dysplasia. So far, 17 children have been described in the world literature. Recently, mutations in the gene encoding EIF2AK3 have been shown to segregate with the syndrome in three affected families. Aims: We aimed to describe the clinical characterization and mutation analysis of a further child, and full clinical and follow-up details on our first family including the longest surviving child. Methods: Retrospective case notes review of three children presenting to the diabetic unit at our institution; mutation analysis of the EIF2AK3 gene in our most recent patient; and review of the literature on Wolcott-Rallison syndrome. Results: Previously unreported phenotypic features in our patients included developmental regression after episodes of hepatic failure, and pachygyria on brain imaging. We have identified a novel 4-base pair deletion (nt 3021–3024 del GAGA) in exon 13, which results in a frameshift and premature stop codon (R908 F/S +22X), causing premature truncation of the protein and abolition of the carboxy- segment of the catalytic domain.
Conclusions: Wolcott-Rallison syndrome causes early-onset diabetes and acute hepatic failure, before epiphyseal dysplasia is manifest. We have identified a novel mutation in EIF2AK3, and prenatal diagnosis may now be offered to affected families.