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Genetics Home Reference: your guide to understanding genetic conditions
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Proopiomelanocortin deficiency

Reviewed February 2014

What is proopiomelanocortin deficiency?

Proopiomelanocortin (POMC) deficiency causes severe obesity that begins at an early age. In addition to obesity, people with this condition have low levels of a hormone known as adrenocorticotropic hormone (ACTH) and tend to have red hair and pale skin.

Affected infants are usually a normal weight at birth, but they are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely obese by age 1. Affected individuals experience excessive hunger and remain obese for life. It is unclear if these individuals are prone to weight-related conditions like cardiovascular disease or type 2 diabetes.

Low levels of ACTH lead to a condition called adrenal insufficiency, which occurs when the pair of small glands on top of the kidneys (the adrenal glands) do not produce enough hormones. Adrenal insufficiency often results in periods of severely low blood sugar (hypoglycemia) in people with POMC deficiency, which can cause seizures, elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia), and a reduced ability to produce and release a digestive fluid called bile (cholestasis). Without early treatment, adrenal insufficiency can be fatal.

Pale skin that easily burns when exposed to the sun and red hair are common in POMC deficiency, although not everyone with the condition has these characteristics.

How common is proopiomelanocortin deficiency?

POMC deficiency is a rare condition; approximately 50 cases have been reported in the medical literature.

What genes are related to proopiomelanocortin deficiency?

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 sugar 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.

Related Gene(s)

Changes in this gene are associated with proopiomelanocortin deficiency.

  • POMC

How do people inherit proopiomelanocortin deficiency?

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.

Where can I find information about diagnosis or management of proopiomelanocortin deficiency?

These resources address the diagnosis or management of proopiomelanocortin deficiency and may include treatment providers.

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development: How are Obesity and Overweight Diagnosed? (http://www.nichd.nih.gov/health/topics/obesity/conditioninfo/pages/diagnosed.aspx)
  • Gene Review: Proopiomelanocortin Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK174451)
  • Genetic Testing Registry: Proopiomelanocortin deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857854)
  • Health Topic: Obesity in Children (http://www.nlm.nih.gov/medlineplus/obesityinchildren.html)
  • MedlinePlus Encyclopedia: ACTH (http://www.nlm.nih.gov/medlineplus/ency/article/003695.htm)
  • National Heart Lung and Blood Institute: How Are Overweight and Obesity Treated? (http://www.nhlbi.nih.gov/health/health-topics/topics/obe/treatment.html)
  • National Institutes of Health Clinical Center: Managing Adrenal Insufficiency (http://www.cc.nih.gov/ccc/patient_education/pepubs/mngadrins.pdf)

You might also find information on the diagnosis or management of proopiomelanocortin deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about proopiomelanocortin deficiency?

You may find the following resources about proopiomelanocortin deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for proopiomelanocortin deficiency?

  • obesity, early-onset, adrenal insufficiency, and red hair
  • POMC deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about proopiomelanocortin deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding proopiomelanocortin deficiency?

adrenal glands ; autosomal ; autosomal recessive ; bile ; bilirubin ; cardiovascular ; cell ; deficiency ; diabetes ; digestive ; gene ; hormone ; hyperbilirubinemia ; hyperphagia ; hypoglycemia ; inherited ; overeating ; peptide ; pigment ; protein ; recessive ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Proopiomelanocortin Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK174451)
  • Krude H, Biebermann H, Gruters A. Mutations in the human proopiomelanocortin gene. Ann N Y Acad Sci. 2003 Jun;994:233-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12851321?dopt=Abstract)
  • Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters 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. (http://www.ncbi.nlm.nih.gov/pubmed/9620771?dopt=Abstract)
  • Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, Grüters 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. (http://www.ncbi.nlm.nih.gov/pubmed/14557433?dopt=Abstract)
  • Krude H, Grüters A. Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab. 2000 Jan-Feb;11(1):15-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10652501?dopt=Abstract)
  • Lee YS. The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature. Ann Acad Med Singapore. 2009 Jan;38(1):34-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19221669?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2014
Published: October 20, 2014