Background: Neonatal diabetes is a rare disorder with an incidence of between 1 in 215 000500 000 live births with approximately 50% having permanent neonatal diabetes (PNDM). Insulin gene (INS) mutations have recently been described as a cause of PNDM.
Objective and hypotheses: To describe clinical features and laboratory manifestations of patient with PNDM due to INS gene mutation and evaluate outcome of management.
Method: Case series study, clinical features, biochemical finding, mutation analysis and management outcome of five cases from five unrelated families were study. All exon of INS genes were amplified from genomic DNA and directly sequenced.
Results: Five cases (three girls and two boys) onset at 152.2±129.4 days of age with gestation age of 37.6±3.3 weeks, birth weight of 2840±856 g. Four out of five cases admitted with the feature of diabetes keton acidosis, blood glucose of 35.6±13.8 mmol/l, HbA1C of 8.98±3.4%. Analysis of all coding regions and exon/intron boundaries of the INS gene showed heterogygous mutation: two patients with splicing mutation at c.188-31G>A, one patient with missense mutation at c.265C>T (p.R89C), one patient with missense mutation at c.127T>A (C43S), one patient with missense mutation at c.286T>C (p.C96R). The oldest patient who has been treated for 12 years has bad blood glucose control for a long time so he has physical retardation but normal mental development and not yet complication. Four smaller patients who have duration of 21±13.8 months have quite normoglycaemic with blood glucose in 58 mmol/l and HbA1C of 6.7±1.4%. All of them have normal motor and mental development.
Conclusion: INS mutation screening is recommended for all diabetic patients diagnosed before 1 year.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology