Dang Anh Duong, Vu Chi Dung, Nguyen Phu Dat, Can Thi Bich Ngoc, Bui Phuong Thao, Nguyen Ngoc Khanh, Tran Minh Dien
Background and objective: Congenital hyperinsulinism (HI) causes severe hypoglycemia in neonates and infants. Molecular genetic results is very important which help clinicians will have suitable treatment. The study aims to describe clinical symptoms, signs of HI patients and to identify mutations in the ABCC8 and KCNJ11, HNF4A and GLUD genes, genotype and phenotype correlations of children with HI.
Methods: A prospective study was conducted on 68 cases with congenital 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]. During the work-up clinical, biochemal was collected. 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: Major clinical symptoms, signs of HI patients when hypoglycemia are: lethargy (69.12%), poor feeding (66.2%), cyanosis (57.4%), ear hair (52.9%), seizure (42.6%), grunting (42.7%), apnea (23.5%), hypotonia (27.9%), diaphoresis (19.12%), unconsciousness (11.7%), hypothermia (2.9%). Glucose level on admission 0.99±0.94 mmol/L, insulin level and C-peptid when hypoglycemia are 214.2±190.6 pmol/L and 1.78±1.5 nmol/L. Gene mutations were detected in 64.29% of cases including mutation of genes ABCC8 (88.89%), KCNJ11 (8.33%), HNF4A (2.78%). Mutation of ABCC8 included homozygous mutations (25%), compound heterozygous mutation (31.25%), one dominant mutation from father (40.63%), one dominant mutation from mother (3.13%). All cases with homozygous mutations, 83.3% of cases with compound heterozygous mutation and 83.3% of cases with one dominant mutation of ABCC8 gene from father did not respond to diazoxide treatment and required 95% pancreatectomy. Other cases with non-mutation usual respond to diazoxide.
Conclusions: 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.
