Congenital Glucagon-like peptide-1 deficiency in the pathogenesis of protracted diarrhea in Mitchell Riley syndrome
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Congenital Glucagon-like peptide-1 deficiency in the pathogenesis of protracted diarrhea in Mitchell Riley syndrome. / Nóbrega, Sara; Monteiro, Mariana P; Pereira-da-Silva, Luís; Pereira, Sofia S; Hartmann, Bolette; Holst, Jens J; Barbosa Silva, Raul; Cordeiro-Ferreira, Gonçalo.
I: Journal of Clinical Endocrinology and Metabolism, Bind 106, Nr. 4, 2021, s. 1084-1090.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Congenital Glucagon-like peptide-1 deficiency in the pathogenesis of protracted diarrhea in Mitchell Riley syndrome
AU - Nóbrega, Sara
AU - Monteiro, Mariana P
AU - Pereira-da-Silva, Luís
AU - Pereira, Sofia S
AU - Hartmann, Bolette
AU - Holst, Jens J
AU - Barbosa Silva, Raul
AU - Cordeiro-Ferreira, Gonçalo
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1210/clinem/dgaa916
DO - 10.1210/clinem/dgaa916
M3 - Journal article
C2 - 33382423
VL - 106
SP - 1084
EP - 1090
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -
ID: 258281126