Endocrine Pathology

, 15:233

First online:

Genetics of congenital hyperinsulinism

  • Jean-Christophe FournetAffiliated withDepartment of Pathology (I-CF), Hôpital Sainte JustineINSERM Unité 383(CJ), Hôpital des Enfants Email author 
  • , Claudine JunienAffiliated withDepartment of Pathology (I-CF), Hôpital Sainte JustineINSERM Unité 383(CJ), Hôpital des Enfants

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous entity and causes severe hypoglycemia in neonates and infants. The clinical heterogeneity is manifested by severity ranging from extremely severe, life-threatening disease to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable.

Recent discoveries have begun to clarify the molecular etiology of this disease in about 50% of cases. Mutations in five different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in the genes ABCC8 and KCNJ11 coding for either of the two subunits of the beta-cell KATP channel (SUR1 and Kir6.2). Recessive mutations of the beta-cell K(ATP) channel genes cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation causes focal adenomatous HI. In other cases, CHI is caused by mutations in genes coding for the beta-cell enzymes glucokinase (GK), glutamate dehydrogenase (GDH), and SCHAD.

However, for as many as 50% of the cases, no genetic etiology has yet been determined. The study of the genetics of this disease has provided important new information regarding beta-cell physiology.

Key Words

Congenital hyperinsulinism genetics beta cells