AB131. Genotype, phenotype of transient neonatal diabetes mellitus
Ngoc Thi Bich Can1, Dung Chi Vu1, Thao Phuong Bui1, Khanh Ngoc Nguyen1, Dat Phu Nguyen2, Maria Craig3, Andrew Hattersley4, Hoan Thi Nguyễn 1
Background and objective: Transient neonatal diabetes mellitus (TNDM) is a rare but remarkable form of diabetes which presents in infancy, resolves in the first months of life, but then frequently recurs in later life. It is caused by overexpression of the imprinted genes PLAGL1 and HYMAI on human chromosome 6q24, ABCC8 or KCNJ11 mutation. Over half of patients with maternal hypomethylation at the TNDM1 locus have additional hypomethylation of other maternally methylated imprinted genes throughout the genome, and the majority of these patients havemutations in the transcription factor ZFP57. This article aims to describe clinical features and laboratory manifestations of patient with TNDM and evaluate outcome of management.
Methods: 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 genes has failed to detect, methylation—specific PCR will be done to detect the loss of methylated region on chromosome 6q24.
Results: Five cases (two girls and three boys) onset at 26.2±11.2 days of age with gestation age of 38.6±2.6 weeks, birth weight of 2,440±512 g. 4/5 patients admitted with the feature of polydipsia, polyuria, macroglossia and diabetes ketone acidosis with pH of 7.11±0.2, blood glucose of 36.64±10.9 mmoL/L, HbA1C of 7.02%±0.96%. Methylation—specific PCR of two patients showed heterozygous mutation in ZFP57; two patients has maternal hypomethylation at the TND differentially methylated region on chromosome 6q24, in there, one methylation signature is characteristic of patients with mutations in ZFP57 in the process of carrying out ZFP57, one patient has heterozygous for the previously reported ABCC8 missense mutation, p.R1183W. All patients stopped insulin after 8.25±5.8 months of treatment. After 32±23 months of insulin stopped, all of them have normal blood glucose and normal HbA1C, four cases have normal development, and one case has mild development delay.
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: Transient neonatal diabetes; ZFP57 mutation
