Liver Disease and Other Comorbidities in Wolcott Rallison Syndrome: Different Phenotype and Variable Associations in a Large Cohort
Background: Wolcott Rallison syndrome (WRS) is caused by recessive EIF2AK3 mutations and characterized by early onset diabetes and skeletal dysplasia. Hepatic dysfunction has been reported in 60% of patients. Aims: To describe a cohort of WRS patients and discuss the pattern and management of their liver disease. Methods: Detailed phenotyping and direct sequencing of EIF2AK3 gene were conducted in all patients. Results: Twenty eight genetically confirmed patients (67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations were detected, of which 2 were novel. The p.S991N mutation was associated with prolonged survival and p.I650T with delayed onset. All patients presented before 25 months with diabetes with variation in the fre