Background: Neonatal diabetes may be defined as hyperglycemia diagnosed within the first 6 months of life which is permanent neonatal diabetes or transient neonatal diabetes. They can result from some gene mutations such as KCNJ11, ABCC8, INS, GCK, … In there, the most common cause of neonatal diabetes mellitus is associated with activating mutations in the KCNJ11 gene, which encodes Kir6.2-a subunit of the ATP-sensitive potassium channel (KATP) of the β cell and ABCC8, which encodes the sulfonylurea receptor (SUR1)-the other subunit of the β-cell KATP channel. ABCC8 and KCNJ11 are located on chromosom 11.
Objective: Determine gene mutation of KCNJ11 and ABCC8 in patients with neonatal diabetes mellitus; assess the results of oral sulfonylureas therapy replacing insulin injection.
Subject: 11 neonatal diabetes mellitus patients with ABCC8 or KCNJ11 mutations are treated in National Hospital of Pediatrics.
Methods: Case series study, collect the symtoms and investigation, DNA was extracted from lymphocyte and analysed gene mutation by PCR or sequencing of KCNJ11, ABCC8. Results: six patients has KCNJ11 mutation: one heterozygous for a missense mutation, R201H (p.Arg201His), two heterozygous for a missense mutation R201C (p.Arg201Cys), one heterozygous for missense mutation R50Q (p.Arg50Gln), one heterozygous for missense mutation p.Gl229Lys, one heterozygous for missene mutation E292G (p.Glu292Gly); five patients with ABCC8 mutations: one missense R1183W (p.Arg1147Trp), one nonsense E747X, one compound heterozygote for missense E747X and nonsense E128K, one herterogygous for A1153G, one compound heterogygous for spilcing c.3401-1G>A and novel missense E1507Q (p.Glu1507Gln). 10/11 patients successfully transferred to sulfonylureas and did not need insulin injections, and one patient with novel mutation is treating with insulin.
Conclusion: It is important for patients with neonatal diabetes mellitus to analysis mutaions for chosing a suitable therapy and progress.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology