Identification of an ABCC8 variant in a kindred with transient diazoxide responsive hyperinsulinism

Abstract

Congenital hyperinsulinism is a rare disorder characterized by hypoglycemia and inappropriately elevated insulin levels. The genetics of congenital hyperinsulinism is complex, with the most common cause being pathogenic variants in the ATP-sensitive potassium channel. Depending on the parent of origin, patients may present with focal or diffuse hyperinsulinism. Typically, patients with focal hyperinsulinism are non-responsive to diazoxide and likely progress to surgical therapy. However, there can be exceptions to these rules. We evaluated two siblings with congenital hyperinsulinism. Genetic testing identified a paternally inherited variant in ABCC8. One sibling had significant neonatal hypoglycemia requiring diazoxide for several years before weaning off daily diazoxide, whereas the second sibling experienced transitional hypoglycemia in the neonatal period but only requires diazoxide therapy during periods of intercurrent illness. This case highlights the importance of genetic testing for congenital hyperinsulinism.

Keywords

• congenital hyperinsulinism
• genetics
• diazoxide