The genetic basis of neonatal diabetes mellitus.

Neonatal diabetes mellitus is a rare condition occurring within the first few months of life that can either be permanent or transient. Various genetic defects responsible for both permanent and transient neonatal diabetes have been identified. ATP-sensitive potassium (KATP) channels are key regulators of nutrient-induced insulin secretion in pancreatic beta cells. Activating mutations of the KATP channel, which prevent closure of the channel and thus inhibit insulin secretion, are now known to be the predominant cause of permanent neonatal diabetes. Transient neonatal diabetes may also be associated with activating mutations of the KATP channel. However, the majority of cases of transient neonatal diabetes have a mutation that maps to a locus on the long arm of chromosome 6, and mutations in two overlapping genes, ZAC and HYMA1, have been identified as the predominant cause of transient neonatal diabetes. These findings provide important insights into the molecular and genetic basis in the broad spectrum of diabetes mellitus.