ABSTRACT
Objective:To investigate the clinical and molecular genetic characteristics of 6q24-related transient neonatal diabetes mellitus (6q24-TNDM).Methods:The clinical data of two neonates with 6q24-TNDM admitted to Shanghai Children's Hospital, Shanghai Jiao Tong University in 2017, were retrospectively collected. The methylation levels of 16 cytidine-phosphate-guanosine (CpG) sites from the methylated differentially modified region (DMR) in 6q24 were quantitatively analyzed by pyrosequencing.Results:Case 1, aged 5 d, was born at 37 +4 gestational weeks due to fetal growth restriction, and case 2 was 11-days old and born at 38 +2 gestational weeks. Both infants were male and small for age. They were born through a cesarean section. The birth weight of case 1 and case 2 were 2 340 g and 2 600 g, respectively. They were admitted due to hyperglycemia with blood glucose of 12.95 and 8.00 mmol/L on admission, respectively. Physical examination showed slightly poor skin elasticity and thin subcutaneous fat. Laboratory examination revealed lower serum insulin (<1.39 and 3.94 pmol/L) and peptide C (0.05 and 0.14 nmol/L) levels, positive results of urine glucose, negative tests for urine ketone, serum anti-glutamic acid decarboxylase antibody, anti-insulin antibody, and islet cell antibody in both cases. Normal size of the pancreas was observed by ultrasonography. The infants were improved and were discharged after subcutaneous insulin infusion for more than two weeks. The treatment was discontinued at 69 d and 42 d postnatally for case 1 and case 2. Prenatal diagnosis of the two infants showed normal karyotypes and uniparental disomy of chromosome 6 indicated by single nucleotide polymorphism chip. No pathogenic mutations were detected by next-generation sequencing after admission. The methylation levels of 16 CpG sites in DMR of 6q24 in the two cases, which were quantitatively analyzed by pyrosequencing, were lower than 10% (normal value in healthy matched controls: 40%), indicating an obvious hypomethylation. Conclusions:For children with TNDM who are small for gestational age at birth, presenting hyperglycemia with decreased serum insulin and C-peptide levels, pyrosequencing can be used to quantitatively analyze the methylation levels of CpG sites in 6q24 DMR, which can quickly and directly assist in the diagnosis of 6q24-TNDM, thereby contributing to the treatment and prognosis assessment.