Wolcott-Rallison syndrome

Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (MIM 226980) is an autosomal recessive disorder characterized by insulin-dependent diabetes developing in the newborn or neonatal period and multiple epiphyseal dysplasia. Many patients have recurrent episodes of hepatitis or frank hepatic failure followed by developmental regression or retardation. Other findings may include: diffuse demineralization with an early tendency to fracture, kyphosis, lordosis, platyspondyly, bowed femora, growth retardation, and renal failure. Wolcott-Rallison syndrome is caused by mutations in the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) gene. This gene encodes a kinase that phosphorylates alpha subunit of eukaryotic translation initiation factor 2 (EIF2A). EIF2A regulates the synthesis of unfolded proteins in the endoplasmic reticulum and is implicated in the differentiation of pancreatic islet ß cell progenitors. To date several mutations have been described in the EIF2AK3 gene.