Congenital Glucagon-like peptide-1 deficiency in the pathogenesis of protracted diarrhea in Mitchell Riley syndrome.

Context Mitchell Riley syndrome (MRS) due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. 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. Objectives To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of MRS protracted diarrhea. Design Two case report descriptions. Setting Tertiary pediatric hospital. Intervention "Off-label" treatment with liraglutide. Patients We report two children diagnosed with MRS, 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. Main outcome To evaluate whether GLP-1 analogue therapy could improve MRS 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. Conclusions Congenital GLP-1 deficiency was identified in patients with MRS. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.