Non-surgical Treatment May be Appropriate for Most Chinese Children With Monogenic Congenital Hyperinsulinism Based on a Retrospective Study of 121 Patients.

There is a notable absence of extensive Chinese studies involving monogenic congenital hyperinsulinism (CHI). The purpose of this large retrospective Chinese cohort with monogenic CHI from a national children's medical center was to analyze the genetic and clinical characteristics. We compared clinical characteristics grouped by genotypes based on CHI-targeted next-generation sequencing (tNGS) and performed subgroup analyses by onset time. Totally, 121 non-consanguineous patients were enrolled. Among them, 79 patients (65.3%) had variants in ATP-sensitive potassium channel () genes (62 heterozygotes and 17 compound heterozygotes), 35 (28.9%) in glutamate dehydrogenase 1 (), and 7 (5.8%) in rare genes (hydroxyacyl-CoA dehydrogenase [], glucokinase [], and hepatocyte nuclear factor 4 alpha []). Ten patients had ATP binding cassette subfamily C member 8 () variants (p.G111R), and 12 had variants (p.S498L), suggesting two potential founder variants. Three variants (p.G1478R, p.L580_S581insFASL, and p.S986 ) and two variants (p.R63W and p.V382I) were previously reported to be associated with diabetes. Non-surgical treatment was effective in 65.9% of patients with variants, while in 100% of those with non- variants. For the subgroup of variants, neonatal-onset patients tended to present with mild symptoms (67.9% versus 19.3%), had a higher proportion of surgical intervention (24.5% versus 3.8%), and displayed higher levels of serum insulin and C-peptide than non-neonatal onset ones ( < 0.001). The absence of homozygous variants in genes and a quite higher proportion of variants than previous cohorts, may explain a high response rate of non-surgical treatment in this study. Surgery might be considered for neonatal-onset children, especially when variants were discovered but not for those carried variants reported to cause diabetes in later life. While expanding the genotypic spectrum, we also highlight the clinical significance of genetic screening.