Congenital Hyperinsulinism: Overview and Clinical Update

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy. This review gives an overview and update of pathogenesis, genetics, diagnosis and management of CHI. This diesease is a genetically heterogeneous disorder with both familial and sporadic variants and is biochemically characterized by an unregulated secretion of insulin from pancreatic beta cells in relation to the blood glucose concentration. To date, there are eight different genes described which lead to CHI. However, in 50% of patients the genetic mechanism is still unknown. The clinical presentation is heterogeneous with regard to age of onset, severity and manner of symptoms. This is explained by different pathogenetic mechanism resulting in inappropriate insulin secretion. An early and rapid diagnosis including initiation of an effective treatment is essential for preventing hypoglycaemic brain damage and neurological sequelae in affected children. Over the last years, substantial progress in diagnostic with 18F-L-dopa positron emission tomography for differentiating diffuse from focal disease and new laparoscopic surgery techniques has been made. In patients with diffuse form of CHI medical treatment with diazoxide, which is ineffective in patients with defects of the KATP channel, is the first line treatment. When medical treatment failed a near-total pancreatectomy has to be considered as a last resort. In patients with focal CHI a limited pancreatectomy can lead to complete cure of the disease. Patients should be managed by centres with a highly experienced team in diagnostic work-up and treatment of CHI.