Wolcott-Rallison syndrome [OMIM#226980] is characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, intellectual disability and cardiovascular anomalies. The majority of cases to date have originated from individuals coming from the Arabian peninsula and vicinity.
Mutations in the EIF2AK3 [OMIM#604032] gene cause Wolcott-Rallison syndrome. EIF2AK3 encodes a translation-regulating kinase present in many tissues that plays an important role in trafficking of proinsulin through the secretory pathway in beta cells.