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

Abstract

Abstract 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.