Abstract 138: Importance of genetic diagnosis in clinical decision making of neonatal diabetes- A short case series with follow-up

Background and Objectives: Neonatal diabetes is defined when onset of diabetes is within 6 months of life. It is characterized into transient, permanent, and syndromic forms. Several monogenetic mutations in beta cells is associated with neonatal diabetes. Various genes are associated with specific inheritance pattern, phenotype, clinical features and treatment. The aim of present study is to implicate the role of genetics in prognosis and treatment outcomes of neonatal diabetes. Case Series Case 1: 2 month old female child presented with diabetic ketoacidosis (DKA). On evaluation C peptide was 0.1 ng/ml and anti-GAD negative. Once acute episode resolved was switched over to subcutaneous insulin with injection Glargine oneunit daily and injection Lisproaccording to blood sugars. Genetic analysis showed homozygous mutation in EIF2AK3gene which is associated with Wolcott Rallison syndrome. The syndrome is associated with earlyonsetpermanentneonataldiabetes, renal, hepatic dysfunction, skeletal dysplasias, pancreatic insufficiency and neutropenia. At present the child does not have any of theabovesyndromic manifestations and need for lifelong insulin therapy is advised and is under regular follow up. Case 2: 2-month-old male child presented with DKA. On evaluation C peptide was 0.05 ng/ml and anti-GAD negative. Once acute illness resolved, blood sugars were maintained with injection Glargine 4 units once daily and injectionLispro according to blood sugars. Genetic analysis showed heterozygous mutation KCNJ11 gene. It is associated with DEND syndrome and permanent neonatal diabetes responding to sulphonylurea. Infant was switched over from insulin therapy to sulphonylureas at 3.5 months of age after a genetic diagnosis was made. Glyburide was up titrated slowly and blood sugars were maintained at a dose of 1 mg /kg/day without insulin. Now HBA1c on follow-up is 7.0%. Case 3: 4 day old very low birth weight baby had persistent high blood sugars with no features of DKA. On evaluation C peptide was 0.029 ng/ml and anti-GAD negative. Blood sugars were maintained with injection Glargine 2 units once daily and injectionLispro according to blood sugars. Genetic analysis revealed homozygous mutation in Glucokinase gene which is associated with permanent neonatal diabetes. The need for lifelong insulin treatment was advised. Conclusion: Genetic analysis should be done as soon as neonatal diabetes is diagnosed. Certain forms of neonatal diabetes like ABCC8 and KCNJ11 may respond to sulfonyl urea thus preventing lifelong insulin therapy. Also genetic analysis may help in differentiating temporary and permanent neonatal diabetes and to look for associated abnormalities.