Background: Congenital hyperinsulinism (CHI) is a condition caused by dysregulated insulin secretion. Compound heterozygous mutations in ABCC8 or KCNJ11 genes account for approximately 13% of CHI mutations and have traditionally been associated with diffuse disease unresponsive to diazoxide.
Objective and hypotheses: To analyse the clinical presentation and response to treatment of patients diagnosed with CHI due to compound heterozygous mutations in the ABCC8 or KCNJ11genes.
Method: Retrospective review of clinical records of all patients diagnosed in our centre with CHI due to compound heterozygous mutations, between 1994 and 2015.
Results: 21 patients were included (11 females). The mean gestational age at birth was 38 weeks (3540 weeks) with an average weight of 4422.9 g (±660.4 g). Hypoglycaemia was identified within the first 18 h of life in 19 patients. The remaining 2 were diagnosed at 3 weeks and 12 months old respectively. Biochemical parameters of CHI were similar in all subjects. Eight patients (38%) had a 18F-DOPA PET scan that revealed diffuse disease in all cases. Regarding management, six patients (28.6%) responded to pharmacological treatment: one child (4.8%) improved with diazoxide and five patients (23.8%) responded to newer pharmacological agents such as octreotide-lanreotide or sirolimus. 14 patients (66.7%) underwent near total pancreatectomy, from this group, eight patients (57.1%) developed diabetes mellitus, five (35.7%) are currently treated with sirolimus±lanreotide and one was cured. One baby who did not respond to diazoxide, presented with severe CHI that resolved spontaneously by the age of 8 weeks. Genetic analysis of both ABCC8 and KCNJ11 was performed, but only mutations of the former were found, of those, 10 mutations had not been previously described.
Conclusion: Due to their heterogeneity in terms of clinical presentation and response to medical therapy, patients with compound heterozygous mutations in the ABCC8 gene, require individualised assessment to achieve the best outcome.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology