Early Postnatal Use of Glibenclamide in Permanent Neonatal Diabetes Secondary to Antenatally Diagnosed <b><i>KJCN11</i></b> Mutation

Abstract

Introduction: Heterozygous activating mutations in KCNJ11 cause both permanent and transient neonatal diabetes. A minority of patients also have neurological features. Early genetic diagnosis has important therapeutic implications as treatment with sulfonylurea provides good metabolic control and exerts a protective effect on neuromuscular function. Case presentation: A term female infant with normal birth weight (2.73 Kg, z-score: -1.69) was admitted to the Neonatal Unit at Addenbrookes Hospital. She had been antenatally diagnosed with KCNJ11 mutation-R201C inherited from her glibenclamide‐treated mother who continued sulfonylurea treatment throughout pregnancy. A continuous glucose monitoring system inserted at 20 hours of age showed progressive rise of blood glucose concentrations, prompting treatment with glibenclamide on day 2 of life. Initial attempts to treat with an extemporaneous solution of glibenclamide (starting dose 0.2mg/kg/day) resulted in inconsistent response and significant hypoglycaemia and hyperglycaemia. A licensed liquid formulation of glibenclamide (Amglidia) at a starting dose of 0.05 mg/kg/day was used with stabilisation of blood glucose profile within 24 hours. Other than a mild transient elevation in transaminase, treatment was well tolerated. At most recent review (age 12 months), the patient remains well with age-appropriate neurodevelopment. Overall glucose control is reasonable with estimated HbA1c of 7.6% (59.9 mmol/mol). Conclusion: Early post-natal glibenclamide treatment of insulin-naïve patients with KATP-dependent neonatal diabetes is safe, provides good metabolic control and has a potential protective effect on neurological function. The formulation of the medicine needs to be carefully considered in the context of the very small doses required in this age group.