AB128. Neonatal diabetes mellitus: genotype, phenotype and outcome
Ngoc Thi Bich Can1, Dung Chi Vu2, Thao Phuong Bui2, Khanh Ngoc Nguyen2, Sarah Flanagan2, Sian Ellard1, Maria Craig3, Dat Phu Nguyen4, Hoan Thi Nguyen2
Background and objective: Neonatal diabetes mellitus (NDM) is a rare (1:300,000-400,000 newborns) but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. Two main groups have been recognized on clinical grounds, transient NDM (TNDM) and permanent NDM (PNDM). This article aims to describe clinical features and laboratory manifestations of patient with NDM and evaluate outcome of management.
Methods and materials: Clinical features, biochemical finding, mutation analysis and management outcome of 24 cases 24 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.
Results: Twenty-four cases (11 girls and 13 boys) onset at 67.3±44 days of age with gestation age of 38.79±2.2 weeks and birth weight of 2,720.8±571.7 g. 9/24 cases admitted with the feature of polydipsia, polyuria and 17 cases with diabetes keton acidosis with pH of 7.13±0.18, blood glucose of 34.8±10.0 mmoL/L, HbA1C of 7.9%±2.9%. Mutation analysis showed six patients with heterozygous for a KCNJ11 missense mutation, seven patients with ABCC8 mutations, four patients with abnormal of chromosom 6, six patients with INS mutation, one patient with EIF2AK3 mutation. The patients have been followed up during 54.4±46.6 months (4 months to 14 years). Five patients with TNDM stop insulin at 8.25±5.8 months of diagnosis: four cases have abnormal of 6q24, one case has ABCC8 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. Nineteen patients with PNDM: 13 cases successfully transferred onto sulfonylureas and did not need insulin injections, six cases require insulin. In there, two cases with DEND syndrome have development delay, others cases have normal mental development.
Conclusions: It is important to perform screening gene mutation for patients with diabetes before 6 months of age to control blood glucose and follow up the patients.
Keywords: Neonatal diabetes mellitus (NDM); transient neonatal diabetes; permanent neonatal diabetes
