ESPE Abstracts

Neonatal diabetes is characterised by hyperglycaemia in the first 6 months of life. Transient neonatal diabetes (TND) is differentiated from permanent neonatal diabetes by its remission in infancy/early childhood, with possible relapse during adolescence in 50% of the cases. Incidence of neonatal diabetes is thought to range from 1:90,000 to 1:160,000. A gene mutation affecting pancreatic beta cells synthesis/secretion of insulin is present in more than 80% of the cases. Overexpression of genes on the 6q24 locus is the most common cause of TND followed by mutations of the ABCC8 or KCNJ11 genes coding for the ATP-dependent potassium channel (KATP) in the pancreatic beta cell. Activating mutations in either of the two genes result in inappropriately open KATP channel despite hyperglycaemia leading to inability of the cell membrane to depolarise and release insulin. Female infant born at 31 weeks’ gestation to non-consanguineous parents, via C-section, after rupture of membrane and breech, weighing 1.440 Kg (50th centile). Uneventful initial course. Incidental finding of hyperglycaemia at day 9 of age on a capillary gas, glucose of 18.2 mmol/l (true glucose 14.4 mmol/L) and highest glucose measurement of 22.2 mmol/L. No ketonaemia/acidosis and no stress factors present. Treatment with Actrapid 0.025 IU/Kg/hour was started. Insulin was titrated accordingly to a maximum of 0.06 IU/Kg/hour and discontinued on day 29 of age. A glycaemic control and study of pancreatic reserve (when hyperglycaemia detected and when insulin discontinued) were assessed. Glibenclamide was due to be started at 0.05 mg/Kg/day in two divided doses, however, infant’s blood glucose levels stabilised at 4-7 mmol/l, decision was made to hold off sulfonylurea treatment. Genetic testing: heterozygous mutation in the ABCC8 gene, leading to a missense mutation in the SUR1 protein. There is no relevant family history, and parents did not show any related mutation. Neonatal hyperglycaemia is a common finding however a genetic mutation should be considered in the absence of contributing factors, with normal birth weight and a later hyperglycaemia (after day 3-5 of age). Genetic testing is important as a specific genetic mutation can significantly alter the treatment and outcome. Patients with activating mutations of either ABCC8 or KCNJ11 respond well to oral sulfonylurea therapy. Despite remission, close glucose monitoring and education of caregivers about diabetes is essential. Long term monitoring is planned (to puberty) with a focus on possible diabetes relapse.