Congenital hyperinsulinism in the Ukraine: a 10-year national study

Front Endocrinol (Lausanne). 2024 Dec 17:15:1497579. doi: 10.3389/fendo.2024.1497579. eCollection 2024.

Abstract

Introduction: Congenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.

Methods: Forty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023. Genetic testing (n=40), 18F-fluorodihydroxyphenylalanin and 68Ga-DOTANOC PET/CT imaging followed by surgical treatment and subsequent histological analysis (n=19) was performed through international collaboration.

Results: Pathogenic variants were identified in 19/22 (86.3%) individuals with persistent CHI (p-CHI) and 8/18 (44.4%) with early remission CHI (er-CHI). Pathogenic variants in the K-ATP channel genes were the only identified genetic cause of p-CHI (ABCC8 (n=17) and KCNJ11 (n=2)) with greater genetic heterogeneity observed in those with er-CHI (ABCC8 (n=3), KMT2D (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and INSR (Donohue syndrome (n=2)). Histological analysis performed on 19 children with persistent CHI confirmed focal disease in 14 (73.7%), diffuse disease in two (10.5%) and atypical histology in three (15.8%). After surgery, complete recovery was observed in all 14 with focal disease, while relapse occurred in three patients with diffuse or atypical histology.

Conclusion: A genetic diagnosis was achieved for 67.5% (27/40) of the cohort with a higher pick-up rate observed in those with p-CHI. The genetics and imaging studies enabled subtype-targeted treatment with surgical cure achieved in all individuals with focal disease.

Keywords: congenital hyperinsulinism; genes; hypoglycemia; outcomes; treatment.

MeSH terms

  • Child
  • Child, Preschool
  • Congenital Hyperinsulinism* / diagnosis
  • Congenital Hyperinsulinism* / epidemiology
  • Congenital Hyperinsulinism* / genetics
  • Congenital Hyperinsulinism* / surgery
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Potassium Channels, Inwardly Rectifying / genetics
  • Registries
  • Sulfonylurea Receptors / genetics
  • Ukraine / epidemiology

Substances

  • Sulfonylurea Receptors
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • ABCC8 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded in whole, or in part, by Wellcome (223187/Z/21/Z). For the purpose of open access, the author has applied a CC BY public copyright license to any Author accepted Manuscript version arising from this submission.