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

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

doi:10.1016/j.soard.2021.04.020

Cited by 36 publications

(30 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three mutations were identified: c.485C>T (T162I), 508A>G (I170V), and 307G>A (V103I). Six individuals composed the SG [four females, two males; 18 ( 10 – 27 ) years old at BS; 50.3 (41.8–61.9) kg/m 2 at BS; three patients with homozygous T162I mutations, two patients with heterozygous T162I mutations, and one patient with heterozygous I170V mutation]. Eight individuals composed the CG [four females, four males; 19.0 (17.8–36.8) years old at BS, 46.2 (42.0–48.3) kg/m 2 at BS or phamacotherapeutic intervention].…”

Section: Resultsmentioning

confidence: 99%

“…Three mutations were identified: c.485C>T (T162I), 508A>G (I170V), and 307G>A (V103I). Six individuals composed the SG [four females, two males; 18 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)…”

Section: Resultsmentioning

confidence: 99%

“…Weight loss 6 months post-BS was not significantly different among patients without and with heterozygous MC4R-d, suggesting that in terms of weight reduction, patients with heterozygous T162I and I170V mutations may benefit from BS as much as MC4R-normal individuals, a finding similar to a previous report ( 17 ). Another recent study has reported no significant weight loss on a patient with compound heterozygous mutation (c.105C>A; p.Y35X, c.110A>T; p.D37V) ( 27 ). Individuals with homozygous T1621 mutation in MC4R and those with compound heterozygous MC4R -d might require multiple surgeries or continued pharmacological intervention to maintain weight loss over a longer period of time.…”

Section: Discussionmentioning

confidence: 98%

“…The mutations reported in our study, both T162I and I170V, are missense mutations and result in partial (T162I) and complete (I170V) loss of function of MC4R gene ( 25 , 26 ). A recent article reported long-term weight loss outcome on bi-allelic mutation in the MC4R gene in a patient who underwent sleeve gastrectomy only ( 27 ). The recent systematic review reported that most of the studies on outcomes of BS in MC4R mutation found no association of MC4R mutations with weight loss ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency

et al. 2022

View full text Add to dashboard Cite

BackgroundMelanocortin-4 receptor (MC4R) mutations are the most common of the rare monogenic forms of obesity. However, the efficacy of bariatric surgery (BS) and pharmacotherapy on weight and glycemic control in individuals with MC4R deficiency (MC4R-d) is not well-established. We investigated and compared the outcomes of BS and pharmacotherapy in patients with and without MC4R-d.MethodsPertinent details were derived from the electronic database among identified patients who had BS with MC4R-d (study group, SG) and wild-type controls (age- and sex-matched control group, CG). Short- and long-term outcomes were reported for the SG. Short-term outcomes were compared between the two groups.ResultsSeventy patients were screened for MC4R-d. The SG [six individuals (four females, two males); 18 (10–27) years old at BS; 50.3 (41.8–61.9) kg/m2 at BS, three patients with homozygous T162I mutations, two patients with heterozygous T162I mutations, and one patient with heterozygous I170V mutation] had a follow-up duration of up to 10 years. Weight loss, which varied depending on mutation type [17.99 (6.10–22.54) %] was stable for 6 months; heterogeneity of results was observed thereafter. BS was found superior to liraglutide on weight and glycemic control outcomes. At a median follow-up of 6 months, no significant difference was observed on weight loss (20.8% vs. 23.0%, p = 0.65) between the SG and the CG [eight individuals (four females, four males); 19.0 (17.8–36.8) years old at BS, 46.2 (42.0–48.3) kg/m2 at BS or phamacotherapeutic intervention]. Glycemic control in patients with MC4R-d and Type 2 diabetes improved post-BS.ConclusionOur data indicate efficacious short-term but varied long-term weight loss and glycemic control outcomes of BS on patients with MC4R-d, suggesting the importance of ongoing monitoring and complementary therapeutic interventions.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency

et al. 2022

View full text Add to dashboard Cite

show abstract

“…HO is a rare form of obesity and, although there is the possibility of considering pediatric bariatric surgery as a therapeutic option for adolescents [1], surgical experience in pediatric HO is virtually non-existent, the long-term effects can be questioned, and serious complications can occur after surgery, so its risk-benefit ratio must be considered with great caution [8]. In a recent long-term outcome study in severe early-onset obesity due to genetic mutations in the leptin-melanocortin signaling cascade, patients initially experienced weight loss after bariatric surgery, but this was followed by substantial weight regain [30].…”

Section: Introductionmentioning

confidence: 99%

Multidisciplinary Approach for Hypothalamic Obesity in Children and Adolescents: A Preliminary Study

et al. 2021

View full text Add to dashboard Cite

Hypothalamic obesity (HO) is delineated by an inexorable weight gain in subjects with hypothalamic disorder (congenital or acquired). The aim of the present study was to evaluate the effect of a multidisciplinary approach on weight trend and metabolic outcome in children and adolescents with hypothalamic disease who were overweight or obese. Thirteen patients (aged 8.1–16.1 years) received a personalized diet, accelerometer-based activity monitoring, and psychological assessment. Height, weight, body mass index (BMI), and serum metabolic parameters were assessed at baseline (T0) and after six months (T1). Metformin was introduced at T1 in four subjects who were then re-evaluated after six months (T2). At T1, weight gain was significantly reduced compared with T0 (0.29 ± 0.79 kg/month vs. 0.84 ± 0.55 kg/month, p = 0.03), and weight standard deviation score (SDS) and BMI SDS did not change significantly, as serum metabolic parameters. The four subjects treated with metformin showed a reduction of weight SDS and BMI SDS at T2. In conclusion, patients treated with our multidisciplinary approach showed, after 6 months, favorable results characterized by decreased weight gain and stabilization of weight SDS and BMI SDS in a condition usually characterized by inexorable weight gain. However, further analysis, larger cohorts, and longer follow-up are needed to confirm these preliminary data.

show abstract

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery

Gong

Huang

et al. 2023

Advanced Biology

View full text Add to dashboard Cite

Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C277X, among which V103I has a relatively high frequency, while other five variants are rare in the population. The prevalence of MC4R carriers in Chinese morbid obese patients (body mass index ≥ 45 kg m−2) is detected as 16.9% in this study. R165W and C277X are loss‐of‐function variants. The patient with R165W achieves excess weight loss (%EWL) as high as 20.6% and 50.3% at 1 and 8 months after surgery, respectively. G233S is reported for the first time in Asia obese population. The patient harboring G233S has a %EWL as 23.3% one month postsurgery. It is concluded that morbid obese patients with rare MC4R variants can benefit from metabolic surgery. More importantly, the choice of surgery procedure and MC4R variant should be taken into consideration for personalized treatment. In the future, a larger size cohort, accompanied with regular and longer follow‐up, would be helpful.

show abstract

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

Cited by 36 publications

References 43 publications

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency

Multidisciplinary Approach for Hypothalamic Obesity in Children and Adolescents: A Preliminary Study

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery

Contact Info

Product

Resources

About