Background: Neonatal diabetes mellitus (NDM) is a relatively rare form of monogenic diabetes and usually presents in the first 69 months of life. In this study, our objective was to report the clinical details, perform a detailed genetic analysis and acquire a clinicalphenotype correlation of our cohort.
Materials and methods: NDM patients referred to SN Endocrine centre between period of Nov 2014 to April 2017 and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 9 months of age were recruited. Molecular genetic analysis was performed at Royal Devon and Exeter Hospital, Exeter.
Results: Fifteen patients (54% males) were diagnosed with NDM (TNDM-1; PNDM-14). Molecular genetic analysis identified a mutation in 12 (78%) patients who had undergone a mutation analysis among which 10 mutations (65%) were definitely pathogenic. The one TNDM case had a KCNJ11 mutation, while in the rest GCK, INS, ABCC8, STAT3, IL2RA, GATA6 mutations were identified. Two PNDM patients had partial response to Sulphonylurea transition, manifest by reduced insulin doses in both and improved DQ in one, while the TNDM case responded to low doses of SU and is now off all therapy for diabetes.
Conclusions: Mutations in GCK, INS and KCNJ11 were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the increased consanguinity within our cohort, as also the combined use of Sanger and targeted Next Gen Sequencing.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology