ESPE Abstracts

Background/aim: Congenital hyperinsulinism (CHI) is a group of genetic disorders characterized by impaired insulin secretion, resulting in recurrent hypoglycemia. CHI is the most common cause of severe and persistent hypoglycemia in infancy and childhood that is associated with an increased risk of seizures, developmental delay and permanent brain damage, with lifelong neurodisability if treatment is delayed. The incidence of CHI is estimated to be approximately 1:28,000–1:50,000 newborns in Western populations. In this study, we present the long-term follow-up of children and adolescents with CHI followed during the last 16 years in a single pediatric center.

Methods: Twenty nine children and adolescents with CHI diagnosed and treated in our center between 2007 and 2023 were enrolled in the study. All patients were under 18 years old. Data on demographics, treatment outcome and follow-up were retrospectively collected.

Results: The median age at diagnosis was the first week of life (range 1 week - 5 years). Sixty two percent (62%) of patients were males (18/29) while 38% (11/29) females. 25% of patients were born with macrosomia (BW>4000g), secondary to fetal overgrowth. Two children had a positive family history of Hyperinsulinism. Genetic testing was performed in all patients, revealing the presence of pathogenic variants in genes associated with CHI in 15 patients (52%), while one patient was diagnosed with Beckwith Weidemann syndrome. Twenty-four patients (83%) commenced on diazoxide, while 4 of them (21%) changed to somatostatin analogues due to inadequate response, whereas 5 (17%) were directly treated with somatostatin analogues. The median follow-up period was 13 years (range 1-16 years). Five patients (17%) developed neurodevelopmental disabilities, while 10 (34%) who were treated with diazoxide developed hypertrichosis. Patients who received long-term somatostatin analogues demonstrated hypertransaminasaemia (21%), cholelithiasis (10%) and 2 required cholecystectomy. No patient underwent pancreatectomy.

Conclusion: Congenital hyperinsulinism is a rare genetic form of persistent hypoglycemia of infancy. It is important to timely initiate proper treatment either with diazoxide or somatostatin analogs to prevent severe hypoglycemic episodes and minimize future neurodevelopmental disability. Molecular investigation aim ing at identifying the underlying genetic cause is incorporated in the diagnostic approach to allow personalized treatment. Nowadays, pharmaceutical approach and development of new pharmaceutic agents are of paramount importance to avoid the invalidating total pancreatectomy that was offered to patients in earlier times.