HYPERINSULINISM Genetics of neonatal hyperinsulinism

Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneous entity. The clinical heterogeneity is mani-fested by severity ranging from extremely severe, life threatening disease to very mild clinical symptoms, which may even be diYcult to identify. Furthermore, clini-cal responsiveness to medical and surgical management is extremely variable. Re-cent discoveries have begun to clarify the molecular aetiology of this disease and thus the mechanisms responsible for this clinical heterogeneity are becoming more clear. Mutations in 4 diVerent genes have been identified in patients with this clini-cal syndrome. Most cases are caused by mutations in either of the 2 subunits of the â cell ATP sensitive K+ channel (KATP), whereas others are caused by mutations in the â cell enzymes glucokinase and gluta-mate dehydrogenase. However, for as many as 50 % of the cases, no genetic aeti-ology has yet been determined. The study of the genetics of this disease has provided important new information about â cell physiology. Although the clinical ramifi-cations of these findings are still limited, in some situations genetic studies might greatly aid in patient management