Background: 6 patients with neonatal diabetes presenting to a single centre from April 2014 to March 2015 were studied for clinical presentation, biochemical findings of the disorder, genetics and treatment outcomes.
Objective and hypotheses: Six children presenting to a single centre in South India were studied for correlation of disease with clinical features and genetics, suitability of current treatment regimens and treatment outcomes.
Method: Neonatal diabetes was defined as A Diagnosis of Diabetes prior to 9 months of age. Ages at recruitment ranged from 5 days to 18 years. Detailed history and investigations ere obtained and included HbA1C, blood glucose, liver and renal function tests and autoimmune markers. Genetic samples were sent to the Genetics Lab of University of Exeter Medical School.
Results: Genetic mutations were identified in five of the six children. Two children had mutations in INS gene (INS missense mutation, p.R89C; a novel INS intronic mutation, c.188-40C>A), one child in ABCC8 (ABCC8 nonsense mutation, p.W232*, and an ABCC8 missense mutation, p.P254S) and another in KCNJ11(KCNJ11 missense mutation, p.R201C). In another infant with a mutation in KCNJ11,(novel KCNJ11 missense variant, p.R29H) a causal association of the mutation with diabetes could not be proven. Two children with INS mutations and the child without an identified mutation have been continued on insulin. ABCC8 and KCNJ11 mutation children are being transitioned onto Sulphonylurea. The neonate with the non-causal KCNJ11 mutation died on 11th day of life, of a massive cerebral infarct, most probably consequent to very high blood sugars at presentation.
Conclusion: With proper genetic analysis, basic research findings can be translated into accurate treatment decisions and good clinical outcomes in neonatal diabetes and especially, the outcomes of transition onto sulphonylurea can be improved.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology