Author(s):
Nóbrega, S ; Monteiro, MP ; Pereira-da-Silva, L ; Pereira, SS ; Hartmann, B ; Holst, JJ ; Barbosa Silva, R ; Cordeiro-Ferreira, G
Date: 2021
Persistent ID: http://hdl.handle.net/10400.17/4733
Origin: Repositório do Centro Hospitalar de Lisboa Central, EPE
Subject(s): Child; Consanguinity; Diabetes Mellitus / blood; Diabetes Mellitus / congenital; Diabetes Mellitus / etiology*; Diabetes Mellitus / genetics; Diarrhea / blood; Diarrhea / congenital; Diarrhea / etiology*; Fatal Outcome; Gallbladder Diseases / blood; Gallbladder Diseases / congenital; Gallbladder Diseases / etiology*; Glucagon-Like Peptide 1 / blood; Glucagon-Like Peptide 1 / deficiency*; Glucagon-Like Peptide 1 / physiology; Glucagon-Like Peptide 1 / physiology; Hepatic Encephalopathy / pathology; Infant; Intestinal Atresia / blood; Intestinal Atresia / etiology*; Mutation, Missense; Portugal; Regulatory Factor X Transcription Factors / genetics; HDE GAS PED; HDE UCI NEO
Description
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.
