AB078. Novel mutation of ABCC8 and KCNJ11 of children with congenital hyperinsulinism

Background and objective: Congenital hyperinsulinism (HI) causes severe hypoglycemia in neonates and infants. To date, more than 350 mutations have been reported in HI patients. However, the genetic screening has failed to define the genetic basis of disease in more than 18% of the cases, demonstrating that pathogenic mechanisms of HI have not been completely elucidated. Patients with HI can have novel mutations that have been announced. The study aims to describe novel mutations of ABCC8 and KCNJ11 of children with HI.

Methods: A prospective study was conducted on 68 cases with HI diagnosed and treated in National Hospital of Pediatric from January 2007 to April 2015. Patients were selected by using inclusion criteria of Hussain K [2008]. Genomic DNA was extracted from peripheral leukocytes using standard procedures. Single exon of KCNJ11; 39 exons of ABCC8; were amplified & sequenced. Sequencing reactions were analyzed on an ABI 3730 capillary sequencer & were compared to published sequences using Mutation Surveyor version 3.24.

Results: In the group cases have ABCC8 mutations (reported mutations are 81.25%, novel mutations are 18.75%), KCNJ11 mutations (reported mutations are 33.33%, novel mutations are 66.67%).

Conclusions: Mutation of ABCC8 and KCNJ11 are common causes of HI. Children with congenital HI causes severe hypoglycemia in neonates and infants with clinical symptoms, signs of hypoglycemia are changeful and not specific for mutation or no mutation. So, children with HI should be analyzed for identifying mutations which helps in making diagnosis and suitable treatment decision.

Keywords: Hyperinsulinism (HI); hypoglycemia