1. Special Nutrition and Respiratory Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
2. Gastrenterology and Hepatology Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
3. Medicine of Woman, Childhood and Adolescence, NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal;
4. Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.
5. Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
6. NICU, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.
7. Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Portugal.
8. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
9. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
10. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Journal of Clinical Endocrinology & Metabolism, 2020 Dec 31:dgaa916. doi: 10.1210/clinem/dgaa916
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 MSD 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 were 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 9 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.
Palavras Chave: enteroendocrine cells, gastric inhibitory polypeptide, glucagon-like peptide-1, liraglutide, Mitchell Riley syndrome, protracted diarrhea