Nationwide Epidemiology and Genetic Background of Persistent Nonsyndromic Congenital Hyperinsulinism in Slovakia

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in children. At least 10 monogenic causes and 28 syndromes have been reported to be associated with CHI. The aim of this study was to evaluate epidemiologic data and genetic background of persistent nonsyndromic CHI in Slovakia.

Based on data from the nationwide Diabgene database of children with persistent hyperinsulinemic hypoglycaemia, 28 children were diagnosed with nonsyndromic CHI during the years 2005-2024. DNA analysis of the most common CHI genes was performed. Epidemiology of CHI was calculated using Slovak demographic data.

The overall incidence of nonsyndromic CHI in Slovakia over the last 20 years was 1:39,804 live births. In 2024, the prevalence was 1:161,802 children younger than 19 years. A genetic cause was identified in 9 children (32%), the most common was CHI due to mutation in ABCC8 gene (n = 4), followed by the KCNJ11 (n = 2), HNF4A (n = 2), and HK1 (n = 1) genes. In diazoxide-unresponsive CHI (n = 6), 5 children had a mutation in the ABCC8 or KCNJ11 genes and one in the HK1 gene. Four children had the focal form based on the paternally inherited recessive mutation and underwent pancreatic surgery.

Nonsyndromic CHI is a rare disease with nationwide incidence in Slovakia of 1:39,804. Diazoxide-unresponsive CHI accounts for 21% of all the cases. A genetic cause was identified in 32% (100% in diazoxide-unresponsive) of children; mutations in the ABCC8 gene were the most prevalent. The type of mutation determines the most appropriate management strategy, including pancreatic surgery.