The updates in molecular genetic mechanisms of neonatal diabetes mellitus / 中华实用儿科临床杂志

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 KCNJII and ABCC8 encoding the Kir6. 2 and SUR1 subunits of KATP channel accounting for 50% . TNDM is caused by defects associated with overexpres-sion of paternally expressed genes in the imprinted region of chromosome 6q24 in 70% cases. About 26% of the defects contain mutations in KCNJII,ABCC8,INS or HNFIB. In vitro and clinical studies suggest that treatment with oral sul-fonylurea can close KATP channel and improve glycemic control and neuropsychological development. However,10% of patients with KCNJII and 15% ABCC8 mutations fail to achieve glycemic control when insulin therapy is switched to o-ral sulfonylureas. Therefore,molecular diagnosis is vital not only in accurate typing but also for better prognostication.