Background: Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1, have also been implicated in TNDM.
Objective and hypotheses: To describe clinical features and laboratory manifestations of patient with TNDM and evaluate outcome of management.
Method: Clinical features, biochemical finding, mutation analysis and management outcome of five cases from five 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 would be done to detect the loss of methylated region on chromosome 6q24.
Results: Five cases (two girls and three boys) onset at 19.5±11.8 days of age with gestation age of 38.6±2.6 weeks, birth weight of 2440±512 g (three cases has BW<3 percentile). Two out of five cases admitted with the feature of diabetic ketoacidosis. The investigation showed pH of 7.14±0.2, HCO3− of 12.17±10.4 mmol/l, blood glucose of 36.6±10.9 mmol/l, HbA1C of 7.02±0.96%. Methylation-specific PCR showed: one case with heterozygous for two difference mutation 7450delT and 7812C>CT, one case with three heterozygous mutations of the ZFP57 gene: a frameshift and premature termination in this coding region (398delT:L133HfsX49), and two further heterozygous mutations in this region (499C>CT:167R>RC and 760C>CT:254L>LF); one case with maternal hypomethylation at TND (6q24), IGF2R (6q27), SNRPN (5q11) and GRB10 (7q12) loci; one case with maternal hypomethylation at the GRB10 and PEG3 loci, characteristic of mutations in ZFP57; one case with heterozygous for ABCC8 missense mutation, p.R1183W. During of treatment and follow up: four out of five patients stopped insulin after 56 months of treatment. Among them, one case had been treated with insulin for a long time and recovered by 18 months of age. Currently, the patients are 51.6±28.9 months old and are euglycemic and normal HbA1C without any insulin or oral hypoglycemic agents. Now four cases have normal development, one case has mild development delay.
Conclusion: It is important to perform screening gene mutation for patients with diabetes diagnosed before 6 months of age to control blood glucose and follow up the patients.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology