Therapy with m-TOR pathway inhibitors in newborn with congenital hyperinsulinism resistant to diasoxide and octreotideTerapia con inhibidores de la vía m-TOR en recién nacidos con hiperinsulinismo congénito resistente a diásóxido y octreotida

Abstract

© 2025Congenital hyperinsulinism (CHI) is a challenging and severe disease in children due to diffuse involvement of the pancreas. Its treatment is based on chronic therapy with diazoxide or octreotide, followed by partial pancreatectomy, which is often not curative. It has been previously described that sirolimus (rapamycin), an mTOR pathway inhibitor (mammalian target of rapamycin), is effective in the off-label treatment of CHI in infants who are refractory to conventional therapies. This report presents the case of a premature 33-week-old infant with a severe form of CHI and a negative mutation in the ABCC8 gene, who responded to rapamycin treatment, showing significant improvement in blood glucose regulation and quality of life. No serious adverse events were observed after 24 months of follow-up. This is the first report of a successful intervention in a pediatric patient in Chile, providing a promising basis for future studies comparing rapamycin with other treatments for the management of congenital hyperinsulinism. The objective of this work is to present a clinical case involving the off-label use of rapamycin in a patient with congenital hyperinsulinism, along with a review of the current literature.FONDECYTFONDECYTCentre for Intercultural and Indigenous Researc