Background: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia which needs a prompt diagnosis and relevant treatment to avoid brain damage. So far, mutations in 11 key genes are known to cause monogenic forms of HI.
Objective and hypotheses: The aim of this study was to characterize the clinical and molecular features of Turkish congenital HI patients and analyze the genotype/phenotype correlations.
Method: Fifty-three patients with HI were included from one pediatric endocrinology center in Istanbul, Turkey. Clinical profile, response to treatment and genetic information of patients and their parents were recorded. Genetic analysis was performed in Exeter, UK.
Results: Mutations were identified in 67.9% (36/53) of all patients. While mutations in ABCC8/KCNJ11 were the commonest genetic cause with a frequency of 47.2% (25/53), HADH and GCK constituted 18.9% (10/53) and 1.9% (1/53), respectively. Among 17 diazoxide-unresponsive patients (32.1% of all), 14 had mutations in ABCC8/KCNJ11 (12 of whom underwent pancreatectomy) and 1 in GCK, mutations were not identified in the remaining two patients. KATP channel mutations in diazoxide-unresponsive patients revealed biparental inheritance in 9 and uniparental inheritance in 5 (all with a paternal origin), while the only mutation in GCK was de novo. Among the diazoxide-responsive patients, (66.0% of all), 10 had mutations in ABCC8/KCNJ11 and 10 had mutations in HADH, constituting all of the HADH mutations in the cohort and all being recessively inherited.
Conclusion: Mutations in ABCC8/KCNJ11 genes are the commonest identifiable genetic cause of congenital HI and are followed by HADH mutations in Turkish patients from our center. Genetic diagnosis of patients is critical to predict the course of the disease.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology