Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome

Sara Nóbrega, Mariana P. Monteiro, Luís Pereira-da-Silva, Sofia S. Pereira, Bolette Hartmann, Jens J. Holst, Raul Barbosa Silva, Gonçalo Cordeiro-Ferreira

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


CONTEXT: 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.

Original languageEnglish
Pages (from-to)1084-1090
Number of pages7
JournalJournal of Clinical Endocrinology & Metabolism
Issue number4
Publication statusPublished - 25 Mar 2021


  • enteroendocrine cells
  • gastric inhibitory polypeptide
  • glucagon-like peptide-1
  • liraglutide
  • Mitchell–Riley syndrome
  • protracted diarrhea


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