Frequency
POMC deficiency is a rare condition; approximately 50 cases have been reported in the medical literature.
Causes
POMC deficiency is caused by mutations in the POMC gene, which provides instructions for making the proopiomelanocortin protein. This protein is cut (cleaved) into smaller pieces called peptides that have different functions in the body. One of these peptides, ACTH, stimulates the release of another hormone called cortisol from the adrenal glands. Cortisol is involved in the maintenance of blood glucose levels. Another peptide, alpha-melanocyte stimulating hormone (α-MSH), plays a role in the production of the pigment that gives skin and hair their color. The α-MSH peptide and another peptide called beta-melanocyte stimulating hormone (β-MSH) act in the brain to help maintain the balance between energy from food taken into the body and energy spent by the body. The correct balance is important to control eating and weight.
POMC gene mutations that cause POMC deficiency result in production of an abnormally short version of the POMC protein or no protein at all. As a result, there is a shortage of the peptides made from POMC, including ACTH, α-MSH, and β-MSH. Without ACTH, there is a reduction in cortisol production, leading to adrenal insufficiency. Decreased α-MSH in the skin reduces pigment production, resulting in the red hair and pale skin often seen in people with POMC deficiency. Loss of α-MSH and β-MSH in the brain dysregulates the body's energy balance, leading to overeating and severe obesity.
POMC deficiency is a rare cause of obesity; POMC gene mutations are not frequently associated with more common, complex forms of obesity. Researchers are studying other factors that are likely involved in these forms.
Inheritance
POMC deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with this condition each carry one copy of the mutated gene. They typically do not have POMC deficiency, but they may have an increased risk of obesity.
Other Names for This Condition
- Obesity, early-onset, adrenal insufficiency, and red hair
- POMC deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Krude H, Biebermann H, Gruters A. Mutations in the human proopiomelanocortin gene. Ann N Y Acad Sci. 2003 Jun;994:233-9. doi: 10.1111/j.1749-6632.2003.tb03185.x. Citation on PubMed
- Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998 Jun;19(2):155-7. doi: 10.1038/509. Citation on PubMed
- Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, Gruters A. Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab. 2003 Oct;88(10):4633-40. doi: 10.1210/jc.2003-030502. Citation on PubMed
- Krude H, Gruters A. Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab. 2000 Jan-Feb;11(1):15-22. doi: 10.1016/s1043-2760(99)00213-1. Citation on PubMed
- Lee YS. The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature. Ann Acad Med Singap. 2009 Jan;38(1):34-11. Citation on PubMed
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