ESPE Abstracts (2015) 84 P-3-1075


aFirst Department of Pediatrics, Faculty of Medicine at Comenius University, Bratislava, Slovakia; bDIABGENE Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; cDepartment of Intensive Care in Neonatology, Faculty of Medicine at Comenius University, Bratislava, Slovakia

Background: Congenital hyperinsulinism (CHI) is the most common cause of the persistent hypoglycemia in children. Mutations in KCNJ11 and ABCC8 genes coding potassium channel subunits are responsible for a significant proportion of CHI patients. The type of mutation correlates with the type of B-cell hyperplasia (focal or diffuse), and determinates further diagnostics, treatment and prognosis of disorder.

Aims and objectives: The aim of this study was to determine etiology of patients with severe hypoglycemia by DNA analysis, and choose appropriate therapeutic approach based on the result.

Methods: During the period of 10 years (2005–2014) 14 patients with congenital hyperinsulinism were identified throughout Slovakia. In all of them the DNA analysis by Sanger sequencing of the genes KCNJ11 and ABCC8 was performed.

Results: Five patients have been found with a mutation in one of the analyzed genes. Two patients had a diazoxide-resistant focal form of CHI caused by paternally inherited ABCC8 mutations (p.Q444H and c.2694+1G>C, respectively). Subsequently, in both patients pancreatic surgery with the aim to reduce B-cell mass was carried out. In two patients sensitive to diazoxide two different mutations were identified (i.e. dominant p.V17A mutation of the ABCC8 gene, and a novel KCNJ11 mutation p.T180N, respectively). Combination of two recessive mutations in the KCNJ11 gene (p.Q52*; p.R301G) was identified in a 4 months old boy with severe hypoglycemia resistant to diazoxide. Based on the results of DNA analysis we started treatment with octreotide, what in combination with frequent feedings through a gastrostomy led to normalization of glycaemia.

Conclusion: DNA diagnostics allows identification of etiology in congenital hyperinsulinism. In case of channelopathies the type of mutation determinates the most appropriate therapeutic procedure (diazoxide in dominant mutations, surgery in focal forms, and somatostatin analogues in recessive mutations causing diazoxide resistant diffuse forms of CHI).

Funding: This work was supported by the Slovak Research and Development Agency (APVV 0107-12).

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