Loading...
Publication
Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell–Riley Syndrome
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 5.27 MB | Adobe PDF |
Advisor(s)
Abstract(s)
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.
Description
Keywords
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
Citation
J Clin Endocrinol Metab . 2021 Mar 25;106(4):1084-1090
Publisher
Oxford University Press