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

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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.

TidsskriftJournal of Clinical Endocrinology and Metabolism
Udgave nummer4
Sider (fra-til)1084-1090
StatusUdgivet - 2021

ID: 258281126