Clinical characteristics of children with Congenital Hyperinsulinism: Results from the European Registries for Rare Endocrine Conditions (EuRRECa) Project

Abstract

Introduction: Congenital hyperinsulinism (CHI) is a group of rare endocrine disorders characterized by repeated episodes of hypoglycemia caused by an excessive insulin secretion from the pancreas beta cells. The etiopathogenesis, phenotype, treatment, and prognosis of individual CHI cases are variable and not completely described. Aims: To gather and describe clinical and genetic data about CHI cases diagnosed within the large EuRRECa network. Materials and Methods: From July 2018 to March 2020, a total of 17 investigators from 14 European reference centers embedded in EuRRECa programme (https://eurreca.net/) reported 77 cases of CHI using a simple e-Reporting (e-REC) tool. These investigators were subsequently asked to complete a web-based questionnaire that obtained information on the phenotype, diagnostic procedures, genotype, treatment, and long-term sequelae of reported cases. Cases with confirmed CHI genetic etiology and those with no genetic findings were compared. Results: The questionnaire was completed in 55/77 (71%) of reported cases from 9/14 (64%) centers. Out of 55 cases, 44 (80%) had a clinical diagnosis of CHI. Of these, all presented with clinical symptoms of CHI, in 41/44 (93%) laboratory results confirmed the diagnosis. Twenty out of 44 (45%) cases had proven genetic CHI etiology – variants in genes ABCC8 in 13, GLUD1 in 3, GCK in 2, and single cases of KCNJ11 and genetically confirmed Beckwith- Wiedemann syndrome. Thirty-two patients (73%) presented first symptoms within the first 7 days of life. In 41/55 cases, treatment modalities were reported. CHI cases were most frequently treated with intravenous glucose (28 cases), dietary recommendations (35 cases), diazoxide (33 cases), octreotide (4 cases), long-acting octreotide (1 case), and glucagon (1 case) application. Six children underwent surgery, 5 partial and 1 total pancreatectomy. Currently, 28/44 (64%) children have age-appropriate [...].