Long-term outcomes of bariatric surgery in patients with bi-allelic mutations in the POMC, LEPR, and MC4R genes.


Journal

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery
ISSN: 1878-7533
Titre abrégé: Surg Obes Relat Dis
Pays: United States
ID NLM: 101233161

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 10 12 2020
revised: 22 04 2021
accepted: 22 04 2021
pubmed: 5 6 2021
medline: 10 8 2021
entrez: 4 6 2021
Statut: ppublish

Résumé

Gene mutations in the leptin-melanocortin signaling cascade lead to hyperphagia and severe early onset obesity. In most cases, multimodal conservative treatment (increased physical activity, reduced caloric intake) is not successful to stabilize body weight and control hyperphagia. To examine bariatric surgery as a therapeutic option for patients with genetic obesity. Three major academic, specialized medical centers. In 3 clinical centers, we retrospectively analyzed the outcomes of bariatric surgery performed in 8 patients with monogenic forms of obesity with bi-allelic variants in the genes LEPR (n = 5), POMC (n = 2), and MC4R (n = 1). In this group of patients with monogenic obesity, initial bariatric surgery was performed at a median age of 19 years (interquartile range [IQR], 16-23.8 yr). All patients initially experienced weight loss after each bariatric surgery, which was followed by substantial weight regain. In total, bariatric surgery led to a median maximum reduction of body weight of -21.5 kg (IQR, -36.3 to -2.9 kg), median percent excess weight loss (%EWL) of -47.5 %EWL (IQR, -57.6 to -28.9 %EWL). This body weight reduction was followed by median weight regain of 24.1 kg (IQR: 10.0 to 42.0 kg), leading to a final weight change of -24.2 % EWL (IQR: -37.6 to -5.4 %EWL) after a maximum duration of 19 years post surgery. In one patient, bariatric surgery was accompanied by significant complications, including vitamin deficiencies and hernia development. The indication for bariatric surgery in patients with monogenic obesity based on bi-allelic gene mutations and its benefit/risk balance has to be evaluated very cautiously by specialized centers. Furthermore, to avoid an unsuccessful operation, preoperative genetic testing of patients with a history of early onset obesity might be essential, even more since novel pharmacological treatment options are expected.

Sections du résumé

BACKGROUND BACKGROUND
Gene mutations in the leptin-melanocortin signaling cascade lead to hyperphagia and severe early onset obesity. In most cases, multimodal conservative treatment (increased physical activity, reduced caloric intake) is not successful to stabilize body weight and control hyperphagia.
OBJECTIVES OBJECTIVE
To examine bariatric surgery as a therapeutic option for patients with genetic obesity.
SETTING METHODS
Three major academic, specialized medical centers.
METHODS METHODS
In 3 clinical centers, we retrospectively analyzed the outcomes of bariatric surgery performed in 8 patients with monogenic forms of obesity with bi-allelic variants in the genes LEPR (n = 5), POMC (n = 2), and MC4R (n = 1).
RESULTS RESULTS
In this group of patients with monogenic obesity, initial bariatric surgery was performed at a median age of 19 years (interquartile range [IQR], 16-23.8 yr). All patients initially experienced weight loss after each bariatric surgery, which was followed by substantial weight regain. In total, bariatric surgery led to a median maximum reduction of body weight of -21.5 kg (IQR, -36.3 to -2.9 kg), median percent excess weight loss (%EWL) of -47.5 %EWL (IQR, -57.6 to -28.9 %EWL). This body weight reduction was followed by median weight regain of 24.1 kg (IQR: 10.0 to 42.0 kg), leading to a final weight change of -24.2 % EWL (IQR: -37.6 to -5.4 %EWL) after a maximum duration of 19 years post surgery. In one patient, bariatric surgery was accompanied by significant complications, including vitamin deficiencies and hernia development.
CONCLUSION CONCLUSIONS
The indication for bariatric surgery in patients with monogenic obesity based on bi-allelic gene mutations and its benefit/risk balance has to be evaluated very cautiously by specialized centers. Furthermore, to avoid an unsuccessful operation, preoperative genetic testing of patients with a history of early onset obesity might be essential, even more since novel pharmacological treatment options are expected.

Identifiants

pubmed: 34083135
pii: S1550-7289(21)00233-1
doi: 10.1016/j.soard.2021.04.020
pii:
doi:

Substances chimiques

MC4R protein, human 0
Receptor, Melanocortin, Type 4 0
Pro-Opiomelanocortin 66796-54-1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1449-1456

Informations de copyright

Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Auteurs

Christine Poitou (C)

Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, CRNH Ile de France, F-CRIN/FORCE Network Paris, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France.

Lia Puder (L)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, Berlin, Germany; Department for Pediatric Endocrinology and Diabetology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Beatrice Dubern (B)

Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France; Pediatric Nutrition and Gastroenterology Department, Assistance Publique-Hôpitaux de Paris, Trousseau Hospital, Paris, France.

Philipp Krabusch (P)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, Berlin, Germany; Department for Pediatric Endocrinology and Diabetology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Laurent Genser (L)

Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France; Department of Hepato-Biliary and Pancreatic Surgery, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.

Susanna Wiegand (S)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Center for Social-Pediatric Care/Pediatric Endocrinology and Diabetology, Berlin, Germany.

Hélène Verkindt (H)

CHU Lille, Endocrine and Metabolic Surgery, Integrated Center for Obesity, Lille, France.

Arvid Köhn (A)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Berlin, Germany.

Reiner Jumpertz von Schwartzenberg (RJ)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Berlin, Germany.

Christa Flück (C)

Paediatric Endocrinology, Diabetology and Metabolism, Department of Paediatrics and Department of BioMedical Research, Bern University Hospital Inselspital and University of Bern, Bern, Switzerland.

François Pattou (F)

CHU Lille, Endocrine and Metabolic Surgery, Integrated Center for Obesity, Lille, France; University of Lille, Lille Pasteur Institute, Inserm U1190, European Genomic Institute for Diabetes, Lille, France; F-CRIN/FORCE Network, Pierre Bénite, Lyon, France.

Martine Laville (M)

F-CRIN/FORCE Network, Pierre Bénite, Lyon, France; Département Endocrinologie, Diabète et Nutrition, Hospices Civils de Lyon, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Univ-Lyon, CarMeN Laboratory, Université Claude Bernard Lyon1, F-CRIN/FORCE Network, Pierre Bénite, Lyon, France.

Peter Kühnen (P)

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, Berlin, Germany. Electronic address: peter.kuehnen@charite.de.

Karine Clément (K)

Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, CRNH Ile de France, F-CRIN/FORCE Network Paris, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France.

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Classifications MeSH