AB125. Neonatal diabetes mellitus due to insulin gene mutation
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AB125. Neonatal diabetes mellitus due to insulin gene mutation

Ngoc Thi Bich Can1, Dung Chi Vu1, Thao Phuong Bui1, Khanh Ngoc Nguyen1, Dat Phu Nguyen2, Maria Craig3, Sian Ellard4, Hoan Thi Nguyen1

1Department of Endocrinology, Metabolism and Genetics, Vietnam National Hospital of Paediatrics, Hanoi, Vietnam; 2Pediatric Department, Hanoi Medical University, Hanoi, Vietnam; 3The Children Hospital at Westmead, Sydney, Australia; 4Molecular Genetics, Old Path Lab, Royal Devon & Exeter Hospital, Barrack Road, Exeter, UK

Background and objective: Insulin (INS) gene mutations that cause permanent neonatal diabetes mellitus change single protein building blocks (amino acids) in the protein sequence. These mutations are believed to disrupt the cleavage of the proinsulin chain or the binding of the A and B chains to form insulin, leading to impaired blood sugar control. At least ten mutations in the INS gene have been identified in people with permanent neonatal diabetes mellitus. To describe clinical features and laboratory manifestations of patients with INS gene mutation and to evaluate outcome of management.

Methods: Clinical features, biochemical finding, mutation analysis and management outcome of six cases from six unrelated families were study. All exons of INS gene were amplified from genomic DNA and directly sequenced.

Results: Six cases (three girls and three boys) onset at 129.2±128.8 days of age (median 101.5 days) with gestation age of 37.3±3.0 weeks, birth weight of 2,816.6±767.8 g. Five out of six patients admitted with the feature of diabetic ketoacidosis with pH of 7.04±0.22; plasma glucose levels were 34.3±12.7 mmoL/L, HbA1C of 9.75%±3.5%. Mutation analysis of the INS gene showed: heterozygous for a novel missense mutation (c.127T > A; C43S) in exon 2 in one case; heterozygous for a splicing mutation c.188-31G > A in intron 2 in two cases; heterozygous for a missense mutation c.286T > C in exon 3 in one case; heterozygous for a missense mutation c.265C > T [p.Arg89Cys (p.R89C)] in exon 3 in two cases. After 19.2±13.4 months of insulin treatment, 4/5 patients have normal development with DQ 80-100%, HbA1C of 6.85%±0.49%, quite normal blood glucose levels. The case with c.127T > A mutation treated with insulin for 14 years has physical development delay, poor blood glucose control with HbA1C of 11.4%.

Conclusions: 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.

Keywords: Insulin gene mutation (INS gene mutation)

Cite this abstract as: Can NT, Vu DC, Bui TP, Nguyen KN, Nguyen DP, Craig M, Ellard S, Nguyen HT. Neonatal diabetes mellitus due to insulin gene mutation. Ann Transl Med 2015;3(S2):AB125. doi: 10.3978/j.issn.2305-5839.2015.AB125

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