The updates in molecular genetic mechanisms of neonatal diabetes mellitus

Abstract

Neonatal diabetes mellitus(NDM) occurs within the first 6 months of life.Depending on clinical outcomes, it is classified into transient neonatal diabetes mellitus(TNDM) and permanent neonatal diabetes mellitus(PNDM). TNDM, which accounts for 50% of NDM goes into remission after treatment for an average period of 12 weeks, but relapse in puberty and early adulthood.PNDM, on the other hand, is a lifelong disease without remission.The clinical features of TNDM and PNDM overlap, and the typing is based on clinical remission on follow-up.More than 20 pathogenic genes have been identified in PNDM, of which the most common are KCNJ11 and ABCC8 encoding the Kir6.2 and SUR1 subunits of KATP channel accounting for 50%.TNDM is caused by defects associated with overexpression of paternally expressed genes in the imprinted region of chromosome 6q24 in 70% cases.About 26% of the defects contain mutations in KCNJ11, ABCC8, INS or HNF1B.In vitro and clinical studies suggest that treatment with oral sulfonylurea can close KATP channel and improve glycemic control and neuropsychological development.However, 10% of patients with KCNJ11 and 15% ABCC8 mutations fail to achieve glycemic control when insulin therapy is switched to oral sulfonylureas.Therefore, molecular diagnosis is vital not only in accurate typing but also for better prognostication. Key words: Neonatal diabetes mellitus; Genetics; Sulfonylureas