Background: Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic β-cells. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2). Severe forms of congenital HH are caused by inactivating mutations in ABCC8 and KCNJ11, which encode the two components of the pancreatic β-cell ATP-sensitive potassium channel.
Objective and hypotheses: Our aim is to identify mutations in the ABCC8 and KCNJ11, HNF4A and GLUD genes, and to describe genotype and phenotype correlations of Vietnamese children with congenital hyperinsulinism.
Method: A prospective study was conducted on 99 cases with congenital hyperinsulinism diagnosed and treated at Vietnam National Childrens Hospital from January 2007 to March 2016. Patients were selected by using inclusion criteria of Hussain K (2008). All exons of ABCC8; KCNJ11, HNF4A and GLUD1 were amplified from genomic DNA and directly sequenced.
Results: Mutations were identified in 50 cases (50.5%) including mutations of ABCC8 gene (44 cases; 44.4%), Among these cases 25 with homozygous/compound heterozygous of ABCC8 and 19 cases with one paternal/maternal mutation of ABCC8 gene); KCNJ11 (five cases; 5.1%), HNF4A (one case; 1.0%). 100% of cases with homozygous/compound heterozygous recessive mutations or one paternal dominant mutation of ABCC8 gene did not respond to diazoxide treatment and required 95% pancreatectomy or octreotide injection. Other cases without identified mutations responded to diazoxide and/or glucose infusion.
Conclusion: Children with congenital hyperinsulinism should be performed mutation analysis which helps in making diagnosis and treatment decision. Families of children with congenital hyperinsulinism should be given genetic counseling. Prenatal diagnosis should be performed as well as follow-up and treatment should be given to children with congenital hyperinsulinism immediately after birth.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology