HYPERINSULINISM Genetics of neonatal hyperinsulinism

Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneous entity. The clinical heterogeneity is manifested by severity ranging from extremely severe, life threatening disease to very mild clinical symptoms, which may even be diYcult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Recent 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 clinical 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 glutamate dehydrogenase. However, for as many as 50% of the cases, no genetic aetiology has yet been determined. The study of the genetics of this disease has provided important new information about â cell physiology. Although the clinical ramifications of these findings are still limited, in some situations genetic studies might greatly aid in patient management. (Arch Dis Child Fetal Neonatal Ed 2000;82:F79–F86)