Background: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes.
Investigations: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy.
Diagnosis: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide.
Management: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.