Neonatal Diabetes: the importance of genetic testing

Abstract

Introduction : we present 2 cases of neonatal diabetes. Mutations in ABCC8 and KCNJ11 genes encoding for the pancreatic KATP channel can lead to transient neonatal diabetes (TNDM) as well as permanent neonatal diabetes (PNDM). KATP channel mutations causing TNDM typically result in diabetes being diagnosed before 6 months of age. Majority of neonatal diabetes patients with KATP channel mutations can be managed with sulphonylureas. Methods : sequence analysis of the ABCC8, KCNJ11, INS and EIF2AK3 genes. Results : case 1: a 9-day old male who presented with jaundice for 3 days and fever for a day. On presentation, baby was febrile, lethargic, with no primitive reflexes. A diagnosis of bilirubin encephalopathy and sepsis was made. On presentation, serum bilirubin was 902 micromil/dl and dropped to 70micromil/dl after 48hours of intensive phototherapy and IV rehydration. On day 3 of admission, infant was noticed to be severely dehydrated although his diapers were soaked with urine. Investigations showed: Random blood sugar 33.1, glucosuria 3+, ketonuria 2+, and enterobacter sepsis. He was managed with insulin infusions and IV antibiotics. By 4th week, baby no longer required insulin, was tolerating full feeds and temperature had settled. Blood sugars have remained within normal range. Sequence analysis of the ABCC8, KCNJ11, INS and EIF2AK3 genes did not identify a pathogenic mutation. Case 2: a 16 week old baby bought to the ER on account of severe weight loss despite good appetite. Random blood sugar on presentation was 33.3mmol/l . Baby was was managed for DKA and discharged home on human premix insulin 30/70 after 2 months of hospital stay. Genetic testing revealed a mutation in the KCNJ11 gene. Baby was switched to glibenclamide, and blood sugars have remained stable. Conclusion : a diagnosis of diabetes before 6 months of age warrants genetic testing to guide treatment decisions.