Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene

Aims/hypothesis Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the K-ATP channels in pancreatic beta cells are a common cause of neonatal diabetes. One-third of patients also have developmental delay, which probably results from mutated K-ATP channels in muscle, nerve and brain. Sulfonylureas, which bind to the sulfonylurea receptor 1 subunit of the K-ATP channel, can replace insulin injections in patients with KCNJ11 mutations. The aim of this study was to investigate the long-term outcome and impact on neurological features of sulfonylurea treatment. Methods We report the response to sulfonylurea treatment in a boy with neonatal diabetes and marked developmental delay resulting from the KCNJ11 mutation V59M. Results Glibenclamide (glyburide) treatment was started at 23 months and resulted in insulin being discontinued, lower overall glycaemia, reduced glucose fluctuations and reduced hypoglycaemia. Good control (HbA(1c) 6.5%) was maintained 2 years after discontinuing insulin, despite a reduction in the glibenclamide dose (from 0.41 to 0.11 mg center dot kg(-1)center dot day(-1)). Within 1 month of starting glibenclamide there was marked improvement in motor function, resulting in the patient progressing from being unable to stand unaided to walking independently, but there was no improvement in mental function. Conclusions/interpretation This 2-year follow-up of a patient highlights that sulfonylurea treatment can result in prolonged, excellent glycaemic control and may improve motor features, but not mental features, associated with KCNJ11 mutations. This suggests that the neurological actions of sulfonylurea are initially principally on peripheral (nerve or muscle) rather than on central (brain) K-ATP channels. Early molecular diagnosis is important in patients with neonatal diabetes and neurological features.