ESPE Yearbook of Paediatric Endocrinology

ascheim1@jhmi.edu Obesity (Silver Spring) 2022, 30(5):973–981 https://doi.org/10.1002/oby.23385

Brief Summary: This review analyzes the outcomes after bariatric procedures among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome (BBS), and hypothalamic obesity (HO). The benefit of bariatric surgery in patients with hyperphagic disorders is only temporary or even absent, indicating the strength of perturbation in the regulation of energy homoeostasis in these patients leading to an elevated body weight set-point [9].

This study is of high interest, since patients with genetic or acquired hyperphagic disorders show an early and rapid increase in BMI accompanied by a high risk of weight-related comorbidities [1,2] but classical weight-management strategies as well as pharmaceutical interventions often fail [2,3].

By reviewing 54 publications from 1974 to 2020 with a total of 202 patients (n=114 with PWS, n=43 with MC4R mutations, n=7 with BBS and n=38 with HO), they identified a notable weight loss in PWS patients over all types of bariatric surgery of −24% within 2 years after surgery. However, this was followed by weight regain beginning 3 years after surgery leading to a non-significant weight-change percentage between 0 and 5 years along with a reoperation rate of 12.5% and a death rate of 9.6%.

Patients with MC4R mutations had suboptimal weight loss after gastric bypass [4], weight regain [5] and an increased risk of reoperation [6], whereas patients with HO showed no weight loss after sleeve gastrectomy (n=11), or BMI-decline (n=1), but also band slippage/weight gain (n=8) after band placement [7,8].

This important review shows that also bariatric surgery is not a promising therapy option for patients with hyperphagic disorders, because of high complication rates and suboptimal effectiveness. The satiety impairment due to alterations in hypothalamic signaling pathways, and also modified ghrelin levels in PWS patients is very robust, therefore also behavioral therapy often fails [10].

At the end, obesity in patients with hyperphagic disorders must be accepted as a chronic disease, comorbidities have to be controlled and treated, and aim of the treatment should be a good quality of life. In addition, potent pharmaceutical interventions are needed to overcome these robust mechanisms.

References: 1. Kaur Y et al. A systematic review of genetic syndromes with obesity. Obes Rev 2017, 18:603–634. 2. Butler MG et al. Prader-Willi syndrome-clinical genetics, diagnosis and treatment approaches: an update. Curr Pediatr Rev 2019, 15:207–244. 3. Muscogiuri G et al. Obesity in Prader-Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches. Journal of Endocrinological Investigation, 2021;44, 2057–2070. 4. Jelin EB et al. Melanocortin-4 receptor signaling is not required for short-term weight loss after sleeve gastrectomy in pediatric patients. Int J Obes, 2016; 40:550–553. 5. Moore BS et al. Long-term weight loss in gastric bypass patients carrying melanocortin 4 receptor variants. PLoS One, 2014;9:e93629. DOI: 10.1371/journal.pone.0093629. 6. Bonnefond A et al. Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study. Diabetes Care 2016;39:1384–1392. 7. Muller HL et al. First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity. Klin Padiatr 2007;219:323–325. 8. Weismann D et al. Bariatric surgery for morbid obesity in craniopharyngioma. Clin Endocrinol 2013;78:385–390.9. Lindgren AC. Eating behaviour in Prader-Willi syndrome, normal weight and obese controls. J Pediatr. 2000;137: 50– 55.10. Holsen lM et al. Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity. Int J Obes (Lond). 2012 May; 36(5): 638–647. doi: 10.1038/ijo.2011.204.