Congenital hyperinsulinism. Results of molecular-genetic investigations in a Russian population

Congenital hyperinsulinism (CHI) is a most frequent cause of persistent hypoglycemia in the children during the first year of life. This pathology is biochemically characterized by inadequate secretion of insulin by beta-cells of the pancreas. Congenital hyperinsulinism is a highly heterogeneous condition in terms of clinical manifestations, histological features, and molecular-genetic defects underlying the development of this disorder. A total of 9 genes are known to be involved in pathogenesis of CHI. The majority of the cases (40-60%) are attributable to the defects in KCNJ11 and ABCC8 genes encoding for the ATP-dependent potassium channels in the pancreatic cells. Approximately 15-20% cases are associated with the mutations of GCK and GLUD1 genes participating in the regulation of intracellular glucose metabolism. The results of clinical, hormonal, molecular-genetic, and histological examination of 42 children presenting with congenital hyperinsulinism are reported. These data were used to analyse the genotype-phenotype relationships.