Monogenic obesity

Monogenic
obesity

Monogenic obesity

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Different types of rare genetic causes of hard-to-control hunger and obesity

When a change in one gene leads to hard-to-control hunger (hyperphagia) and obesity, this is called monogenic obesity. This change in the gene can be inherited from parents, in the same way that genes for eye and hair color are passed down.1

There are many types of monogenic obesity, which include rare melanocortin-4 receptor (MC4R) pathway diseases.1 These rare diseases cause hard-to-control hunger and other issues, which you can see below:

Proopiomelanocortin deficiency

Proopiomelanocortin deficiency, also known as POMC (pronounced POM-see) deficiency is caused by a change in the POMC gene.

Usually, the POMC gene provides instructions to help run an important pathway in the brain, the melanocortin-4 receptor (MC4R) pathway. The MC4R pathway tells us when to eat and when we are full. Changes in the POMC gene can stop a part of this pathway from working and prevent this important message from being sent.1,2

What are the signs of POMC deficiency?2,3

  • Excessive eating caused by hard-to-control hunger  
  • Severe childhood obesity
  • Hormone level differences, which a doctor may call endocrine abnormalities

Some people, but not all, may also have:

  • Mildly low thyroid levels (hypothyroidism)
  • Adolescent-onset growth hormone deficiency
  • Delayed puberty caused by hormonal imbalances (hypogonadotropic hypogonadism)
  • Red hair and light skin
  • Liver disease

Leptin receptor deficiency2

Leptin receptor deficiency, also known as LEPR (pronounced LEP-ar) deficiency, is caused by changes to the LEPR gene. The LEPR gene provides the body’s instructions for making a protein called the leptin receptor.

Leptin is a hormone that is produced by the body’s fat cells. It tells our brain when we have enough fat stored and that we don’t need to eat. This important receptor helps the body regulate weight.

When there is a change in the LEPR gene, the leptin receptor cannot function correctly, and leptin cannot attach to the receptor. This means your brain does not get the message that it is full. 

What are the signs of LEPR deficiency?

The main signs of LEPR deficiency include:
 

  • Hard-to-control hunger
  • Severe, early age childhood obesity
  • Delayed puberty (hypogonadotropic hypogonadism)

Weight change in babies with monogenic obesity

Babies with LEPR or POMC deficiency are normal weight at birth but show signs of constant hard-to-control hunger followed by fast, early age weight gain within their first few weeks of life. In early childhood, abnormal eating and food-seeking habits develop, such as fighting with other children over food, hoarding, and secretly hiding food.4,5

What can you do?

If you think you have spotted one or more of these signs in yourself, or your child, download and complete our discussion guide to help prepare for an appointment with your doctor or nurse.

References

1 Huvenne H, et al. Obes Facts. 2016;  9(3): 158-173

2 Fonseca ACP, et al. J Diabetes Complications. 2017; 31(10): 1549-1561

3 Cetinkaya S, et al. J Clin Res Pediatr Endocrinol. 2018; 10(1): 68-73

4 Wabitsch M, et al. Journal of the Endocrine Society. 2022; 6: 1–9

5 Heymsfield SB, et al. H. Obesity (Silver Spring). 2014; 22 Suppl 1(01):  S1-S17