Suspecting patients with rare MC4R pathway diseases

Hyperphagia and early-onset, severe obesity are two key clinical characteristics associated with rare genetic MC4R pathway diseases.

Clinical characteristics

Two key clinical characteristics are associated with rare genetic MC4R pathway diseases:

1. Hyperphagia:

  • Pathological, insatiable hunger and impaired satiety accompanied by abnormal food-seeking behaviors, caused by MC4R pathway impairment2

Symptoms* may include7

  • Persistent preoccupation with food
  • Prolonged time to satiation and shortened duration of satiety
  • Heightened and prolonged feelings of hunger

Behaviors* may include1,9

  • Eating extremely quickly
  • Eating more than optimal quantities of food
  • Distress if food is unavailable
    • Children may exhibit tantrums or persistent negotiation/demand for food4,9
    • Adults may manifest emotional effects including sadness, frustration, irritability, anxiety and/or guilt3
  • Abnormal food-seeking behaviors such as night eating, hiding food, stealing or sneaking food11
  • Eating excessively—not to be confused with binge eating9

*Symptoms and behaviors may range in severity8

2. Early-onset, severe obesity:

  • Usually patients younger than 5 years of age with a body mass index of ≥35 kg/m² or ≥120% of the 95th percentile for age and sex5,10,12,13

Genetic testing

Some rare genetic MC4R pathway diseases (eg, POMC deficiency, LEPR deficiency) are diagnosed genetically, while others, such as Bardet-Biedl syndrome, are clinically diagnosed; however, genetic testing can aid in the diagnosis.4,10

Clinical practice guidelines and experts recommend genetic testing for patients with clinical features of genetic obesity, including hyperphagia and early-onset, severe obesity.6,10,12,13 Early diagnosis of rare MC4R pathway diseases may help inform treatment, including early obesity management.10

If you suspect your patient may have a form of obesity caused by rare genetic variants and would like more information on genetic testing, visit uncoveringrareobesity.com.

Discover more

Expand your knowledge of Bardet-Biedl syndrome (BBS), a rare genetic disease.

Learn more about BBS

BBS, Bardet-Biedl syndrome; MC4R, melanocortin-4 receptor

References

  1. Dykens EM, et al. Obesity (Silver Spring). 2007;15(7):1816-1826.
  2. Eneli I et al. Appl Clin Genet. 2019;12:87-93.
  3. Ervin C, et al. Adv Ther. 2023;40(5):2394-2411.
  4. Forsythe E, Beales PL. Eur J Hum Genet. 2013;21(1):8-13.
  5. Forsyth R, Gunay-Aygun M. GeneReviews. Accessed February 21, 2024. https://www.ncbi.nlm.nih.gov/books/NBK1363
  6. Goodarzi MO. Lancet Diabetes Endocrinol. 2018;6(3):223-236.
  7. Hampl SE et al. Pediatrics. 2023;151(2):e202206064. doi:10.1542/peds.2022-060640.
  8. Haqq AM, et al. Child Obes. Jun 2021;17(4):229-240.
  9. Heymsfield SB, et al. Obesity (Silver Spring). 2014;22(suppl 1):Sl-Sl7. doi:10.1002/oby.20646.
  10. Huvenne H, et al. Obes Facts. 2016;9(3):158-173.
  11. Sherafat-Kazemzadeh R et al. Pediatr Obes. 2013;8(5):e64-e67. doi:10.1111/j.2047-6310.2013.00182.x.
  12. Styne OM, et al. J Clin Endocrinol Metab. 2017;102(3):709-757.
  13. van der Valk ES, et al. Obes Rev. 2019;20(6):795-804.
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