AUTHOR=Globa Evgenia , Christesen Henrik Thybo , Mortensen Michael Bau , Houghton Jayne A. L. , Nielsen Anne Lerberg , Detlefsen Sönke , Flanagan Sarah E. 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1497579

DOI=10.3389/fendo.2024.1497579

ISSN=1664-2392

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 (<italic>ABCC8</italic> (n=17) and <italic>KCNJ11</italic> (n=2)) with greater genetic heterogeneity observed in those with er-CHI (<italic>ABCC8</italic> (n=3), <italic>KMT2D</italic> (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and <italic>INSR</italic> (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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>