AB110. Genotype and phenotype of 107 patients with congenital hyperinsulinism

Background: Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic β-cell. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF1A, 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. Objectives: 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 HH.

Methods: A prospective study was conducted on 107 cases with congenital HH diagnosed and treated at the National Children’s Hospital from January 2007 to February 2017. 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 57 cases (53.3%) including mutations of ABCC8 gene (51 cases; 47.7%), among them 29 with homozygous/compound heterozygous of ABCC8 and 22 cases with one paternal/maternal mutation of ABCC8 gene; mutations of KCNJ11 (5 cases; 4.7%); and HNF4A (1 case; 0.9%). 98.2% 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.

Conclusions: Children with congenital HH should be performed mutation analysis which helps in making diagnosis and treatment decision. Families of children with congenital HH should be given genetic counseling. Prenatal diagnosis should be performed as well as follow up and treatment should be given to children with congenital HH immediately after birth.

Keywords: Congenital hyperinsulinism; hypoglycemia; beta cell disorders