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

Abstract

<b><i>Introduction:</i></b> Heterozygous activating mutations in <i>KCNJ11</i> 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. <b><i>Case Presentation:</i></b> 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 KCNJ<i>11</i> mutation-R201C inherited from her glibenclamide-treated mother who continued sulfonylurea treatment throughout pregnancy. A continuous glucose-monitoring system inserted at 20 h 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 0.2 mg/kg/day) resulted in inconsistent response and significant hypoglycaemia and hyperglycaemia. A licenced liquid formulation of glibenclamide (AMGLIDIA) at a starting dose of 0.05 mg/kg/day was used with stabilization of blood glucose profile within 24 h. 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). <b><i>Conclusion:</i></b> Early postnatal glibenclamide treatment of insulin-naive 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.