Genetics of neonatal hyperinsulinism

Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneo us entity. The clinical heterogeneity is manifested by severity ranging fro m extremely severe, Life threatening disease to very mild clinical symptoms , which may even be difficult to identify. Furthermore, clinical responsive ness to medical and surgical management is extremely variable. Recent disco veries have begun to clarify the molecular aetiology of this disease and th us the mechanisms responsible for this clinical heterogeneity are becoming more clear. Mutations in 4 different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in either of the 2 subunits of the beta cell ATP sensitive K+ channel (K-ATP), wherea s others are caused by mutations in the beta cell enzymes glucokinase and g lutamate dehydrogenase. However, for as many as 50% of the cases, no geneti c aetiology has yet been determined. The study of the genetics of this dise ase has provided important new information about beta cell physiology. Alth ough the clinical ramifications of these findings are still limited, in som e situations genetic studies might greatly aid in patient management.