ESPE Abstracts

Background: Permanent neonatal diabetes mellitus (PNDM) is a rare form of monogenic diabetes with onset less than 6 months of age. Together, activating mutations in KCNJ11 and ABCC8 genes, that encode the Kir6.2 andsulfonylurea receptor 1 (SUR1) subunits, respectively, account for nearly 50% of PNDM cases.

Case report: We present a case reported a child diagnosed with PNDM resulting from a new mutation in the insulin (INS) gene, leading to severe hyperglycemia and ketoacidosis from 5 month of life. Molecular analyses for KCNJ11, ABCC8, GCK, GLIS3 did not show any mutation. We sequenced the INS gene in the proband and her patents, identified the heterozygous missense mutation G32S (c.94G>A, p.Gly32Ser) in the child with diabetes. It has been hypothesized that the mutations in the INS gene disrupt the folding of the proinsulin molecule and result in a bad situation causing endoplasmic reticulum stress and pancreatic beta cell apoptosis. Subjects with this form of diabetes will need lifelong insulin therapy.

Conclusion: Insulin gene mutations appear to be an important cause of neonatal diabetes. We recommend that all the infants with PNDM should undergo genetic analysis before oral sulfonylurea treatment.