Introduction: Neonatal diabetes mellitus (NDM) is a rare (1:300,000400,000 newborns) but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. Two main groups have been recognized, transient NDM (TNDM) and permanent NDM (PNDM).
Objective: To describle clinical features and laboratory manifestations of patient with NDM and evaluate outcome of management.
Subject and methods: Clinical features, biochemical finding, mutation analysis and management outcome of 38 cases from 38 unrelated families were study. All exon of KCNJ11, ABCC8 and INS genes were amplified from genomic DNA and directly sequenced. If the mutation of KCNJ11, ABCC8 and INS has failed to detect, methylation specific PCR will be done to detect the loss of methylated region on chromosome 6q24. If the mutaion of these genes has failed to detect, whole genome sequencing will be done to detect mutaion.
Results: Thirty-seven cases (16 girls and 21 boys) onset at 7-357 days of age (median: 44.5) with gestation age of 39.1±1.9 weeks and birth weight of 2705.5±526.4 g. 9/38 cases admitted with the feature of polydipsia, polyuria and 29 cases with diabetes keton acidosis with pH of 7.12±0.19, blood glucose of 36.24±11.1 mmol/l, HbA1C of 7.86±2.89%. Mutation analysis showed 10 patients with heterozygous for a KCNJ11 missense mutation, 12 patients with ABCC8 mutations, six patients with abnormal of chromosom 6, and six patients with INS mutation, one patient with EIF2AK3 gene mutation, one patient with FOXP3 gene mutation and one patient with EIF2B1 gene mutation. The patients have been follow up during 54.4±46.6 months (4 months 14 years). Ten patients with TNDM stop insulin at 8.25±5.8 months of diagnosis: 6 cases have abnormal of 6q24, two cases has ABCC8 mutation and two cases has KCNJ11 mutation. Now all cases have normoglycemic (blood glucose: 5.0 and 5.9 mmol/l), one patient has mild development delay and four patients has normal development. 27 patients with PNDM: 18 cases successfully transferred onto sulfonylureas and did not need insulin injections, 8 cases require insulin, one case with FOXP3 gene mutation died for immunodeficiency. In there, 2 case with DEND syndrome have development delay, others cases have normal mental development.
Conclusions: It is important to perform screening of gene mutations for patients with diabetes before 12 months of age to control blood glucose and follow up the patients.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology