Background: Congenital hyperinsulinism (CHI) is a cause of severe persistent hypoglycaemia in children. Diazoxide is the first line medical therapy for CHI; however diazoxide is usually ineffective in CHI with KATP channel gene mutations. Patients with no mutations in the KATP channel genes do respond to therapy with diazoxide. There are no previous studies assessing how long diazoxide therapy is needed in those patients with no genetic aetiology identified for the CHI.
Objective and hypotheses: To describe the clinical, biochemical and genetics aspects of a cohort of CHI patients with no genetic aetiology identified and their duration of diazoxide therapy.
Method: Retrospective review of diazoxide-responsive CHI patients admitted to Great Ormond Street Hospital. Data on gestation age, birth weight, maternal risks, age of diagnosis, biochemical and genetic studies on ABCC8 and KCNJ11 were obtained. Follow up data on glycaemic profile, fasting studies, dose of diazoxide and duration of therapy were recorded.
Results: Ten children with diazoxide-responsive CHI and no known with genetic aetiology were identified. They were diagnosed between 9 days and 23 months old, with three presenting as neonates. Three were female and all were born at term with median birth weight of 3.793 kg (2.994.99 kg). There was no history of maternal gestational diabetes mellitus. All responded to diazoxide, with median maximum dose of 11.5 mg/kg per day (520). All were negative for ABCC8 and KCNJ11 mutations. In all patients diazoxide was stopped at a median age of 8.5 years (415); the median duration of diazoxide therapy was 7.25 years (2.914.6). Fasting studies done after stopping diazoxide showed resolution of CHI.
Conclusion: CHI children with no known genetic aetiology may be able to come off diazoxide at some stage during follow up. These children need regular assessments for continuing diazoxide therapy. The molecular mechanism(s) that lead to the gradual improvement in CHI over time are not known.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology