Nóbrega, SMonteiro, MPPereira-da-Silva, LPereira, SSHartmann, BHolst, JJBarbosa Silva, RCordeiro-Ferreira, G2023-11-032023-11-032021J Clin Endocrinol Metab . 2021 Mar 25;106(4):1084-1090http://hdl.handle.net/10400.17/4733Context: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. Objective: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. Methods: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. Results: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. Conclusion: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.engChildConsanguinityDiabetes Mellitus / bloodDiabetes Mellitus / congenitalDiabetes Mellitus / etiology*Diabetes Mellitus / geneticsDiarrhea / bloodDiarrhea / congenitalDiarrhea / etiology*Fatal OutcomeGallbladder Diseases / bloodGallbladder Diseases / congenitalGallbladder Diseases / etiology*Glucagon-Like Peptide 1 / bloodGlucagon-Like Peptide 1 / deficiency*Glucagon-Like Peptide 1 / physiologyGlucagon-Like Peptide 1 / physiologyHepatic Encephalopathy / pathologyInfantIntestinal Atresia / bloodIntestinal Atresia / etiology*Mutation, MissensePortugalRegulatory Factor X Transcription Factors / geneticsHDE GAS PEDHDE UCI NEOjournal article10.1210/clinem/dgaa916