Mutation of ATP-sensitive K+ channels and neonatal diabetes iDEND syndrome

Activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channel gives rise to intermediate developmental delay, epilepsy and neonatal diabetes (iDEND) syndrome, a rare hereditary endocrine metabolic disorder characterized by neonatal diabetes accompanied by developmental delay and muscle weakness, but no epilepsy. The Kir6.2 Val⁵⁹→Met⁵⁹ (V59M) activating mutation is the common cause of iDEND syndrome (>50%). Activating mutation causes iDEND syndrome by inhibiting normal closure of ATP-sensitive K⁺ channel, which leads to reduce insulin secretion. Most of such patients are more sensitive to sulfonylurea. High blood-brain barrier permeability and sulfonylurea receptor 1 (SUR1)-specific drugs are expected to become a major therapy.