Definition:

Familial hyperinsulinemic hypoglycemia (HHF) is the most common cause of persistent hypoglycemia in infancy. Recent studies on the molecular basis of the disease have disclosed specific genetic defects in the regulation of insulin secretion. Seven different loci have been associated with hyperinsulinism: ABCC8, KCNJ11, HADHSC, GCK, GLUD1, SLC16A1, and INSR. Mutations of these loci have significant differences in phenotype and inheritance pattern. The most common genes associated with hyperinsulinism, involve the ABCC8 and KCNJ11 genes that encode the two subunits of the beta-cell ATP-dependent potassium channel. Recessive mutations of these genes cause a severe form of neonatal hypoglycemia that frequently requires near-total pancreatectomy. Diazoxide, a drug that acts as an agonist of the ATP-dependent potassium channel to suppress insulin secretion, is effective in defects associated with mutations of GLUD1 and HADHSC. Diazoxide is often ineffective in mutations of the ATP- dependent potassium channel and may not adequately control hypoglycemia in GCK or SLC16A1 mutations.