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

Christine Poitou, Lia Puder, Beatrice Dubern, Philipp Krabusch, Laurent Genser, Susanna Wiegand, Hélène Verkindt, Arvid Köhn, Reiner Jumpertz von Schwartzenberg, Christa Flück, François Pattou, Martine Laville, Peter Kühnen, Karine Clément

Journal: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 2021;17(8):1449-1456

PMID: 34083135

Full Text on Elsevier Science View on PubMed

Abstract

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

To examine bariatric surgery as a therapeutic option for patients with genetic obesity.

SETTING

Three major academic, specialized medical centers.

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

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

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.

Address: 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.; 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.; 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.; 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.; 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.; CHU Lille, Endocrine and Metabolic Surgery, Integrated Center for Obesity, Lille, France.; 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.; Paediatric Endocrinology, Diabetology and Metabolism, Department of Paediatrics and Department of BioMedical Research, Bern University Hospital Inselspital and University of Bern, Bern, Switzerland.; 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.; 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.; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, Berlin, Germany. Electronic address: [email protected].

DOI: 10.1016/j.soard.2021.04.020

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MeSH Terms: Adult, Bariatric Surgery, Humans, Mutation, Obesity, Morbid, Pro-Opiomelanocortin, Receptor, Melanocortin, Type 4, Retrospective Studies, Treatment Outcome, Young Adult