Genetic characteristics and clinical management of patients with diazoxid-unresponsive congenital hyperinsulinism in Slovakia

Denisa Lobotkova; Martina Miňova; Simona Tarnokova; Zuzana Dobiašova; Martina Škopkova; Daniela Gašperikova; Juraj Stanik

doi:10.1530/endoabs.110.EP696

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Endocrine Abstracts (2025) 110 EP696 | DOI: 10.1530/endoabs.110.EP696

ECEESPE2025 ePoster Presentations Fetal and Neonatal Endocrinology (27 abstracts)

Genetic characteristics and clinical management of patients with diazoxid-unresponsive congenital hyperinsulinism in Slovakia

Denisa Lobotková ¹ , Martina Miňová ² , Simona Tárnoková ³ , Zuzana Dobiašová ⁴ , Martina Škopková ⁴ , Daniela Gašperíková ⁴ & Juraj Staník ^1,4

Author affiliations

¹Faculty of Medicine at Comenius University and National Institute of Children´s Diseases, Department of Pediatrics, Bratislava, Slovakia; ²Faculty of Medicine of the Pavol Jozef Šafárik University in Košice and Children`s University Hospital, Košice, Slovakia; ³National Institute of Children´s Diseases, Bratislava, Slovakia; ⁴Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia

JOINT3469

Background: One of the critical distinguishing features of children with congenital hyperinsulinism (CHI) is diazoxid responsivness. In diazoxide-unresponsive (DU) patients molecular analysis provides information on the pancreatic histological subtype (i.e. focal vs diffuse) and determinates the most appropriate management strategy. Inactivating mutations in the ABCC8 and KCNJ11 genes are the most common, followed by mutations in GCK and HK1 gene. Recently, important advances have been made in CHI, including newly described molecular mechanisms, novel imaging techniques and therapeutic options.

Aims and objectives: The aim of this study was to evaluate genetic background and clinical management of the patients with DU-CHI in Slovakia.

Patients and Methods: Based on the data from the Slovak nationwide database of children with persistent hyperinsulinemic hypoglycaemia, 6 (22%) of 28 children with CHI were DU since 2005. In all of the individuals DNA analysis of the most common CHI genes was performed.

Results: In all of the six children with a DU-CHI a causal mutation was identified. Four children (66%) had focal form of CHI based on the paternally inherited recessive mutation, i.e. c.1332G>T (2 patients) and c.2694+1G>C in the ABCC8 gene, and c.498_502delinsAG in the KCNJ11 gene. All of them successfully underwent partial pancreatectomy. One boy had inherited two heterozygous mutations c.154C>T and c.901C>G of the KCNJ11 gene in the trans position, and since diagnosis is treated with somatostatin analogues. A de novo deletion encompassing the 151bp regulatory silencer region in intron 2 of the HK1 gene was detected in one girl with a severe clinical course of CHI using digital PCR (dPCR).

Conclusions: DU forms account for 22% of CHI in Slovakia. Genetic cause was identified in all six children; four had a focal form based on the paternally inherited ABCC8 or KCNJ11 mutations, and two children had a diffuse form based on the KCNJ11 and HK1 mutations, respectively. The type of mutation determinates the most appropriate treatment strategy in patients with DU-CHI, including use of somatostatin analogues and pancreatic surgery.Grant support: VEGA 1/0659/22