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

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.