• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

POMC Deficiency


Last updated: 03/06/2023
Years published: 2023


NORD gratefully acknowledges Prof. Dr. Martin Wabitsch, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany for assistance in the preparation of this report.

Disease Overview


POMC deficiency affects the way the body stores and uses energy. The main symptoms include constant hunger and excessive feeding, known as hyperphagia. Hyperphagia leads to obesity by one year of age and without treatment people with POMC deficiency remain obese throughout life. Other symptoms include low levels of a hormone called adrenocorticotropic hormone (ACTH) and adrenal insufficiency, which can be fatal if not treated early. Many individuals with POMC deficiency also have pale skin and hair. POMC deficiency is caused by changes (pathogenic variants or mutations) in the POMC gene and is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Treatment is available for people with POMC deficiency over the age of six using a drug called setmelanotide.


POMC deficiency was first described in 1998. This condition is rare, making it difficult to predict exactly how it will affect someone with a new diagnosis of this condition. It is one of several conditions that include early-onset obesity, and these conditions can be difficult to distinguish from each other without a careful physical examination and genetic testing.

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  • obesity due to pro-opiomelanocortin deficiency
  • POMC
  • obesity, adrenal insufficiency and red hair due to POMC deficiency
  • obesity, early-onset, with adrenal insufficiency and red hair (OBAIRH)
  • proopiomelanocortin deficiency
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Signs & Symptoms

Most individuals diagnosed with POMC deficiency have early-onset obesity and adrenal insufficiency, a condition in which the adrenal glands don’t work correctly. The first symptom of POMC deficiency is often very low blood sugar (hypoglycemia) related to adrenal insufficiency and low levels of ACTH, an important hormone made by the pituitary. ACTH is necessary for the adequate production of cortisol in the adrenal gland. If left untreated, adrenal insufficiency may lead to liver failure and less commonly, death. Infants with POMC deficiency have a normal birth weight but are constantly hungry (hyperphagia) and gain weight very quickly. Obesity is common by age one. Children and adults with this condition have continuous hunger, obesity and behavior problems related to food and eating. Obesity may become severe, leading to other health problems. Some people have a low functioning thyroid gland and are shorter than average. Delayed or absent puberty has also been reported. Many people with POMC deficiency also have pale skin and light or red hair.

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POMC deficiency is caused by pathogenic variants (mutations) in the POMC gene. The POMC gene works with other genes to help signal the body when it’s time to eat and when it has had enough food. When the POMC gene doesn’t work correctly, these signals don’t exist and a person with POMC deficiency feels hungry all the time. In addition, the protein made by the POMC gene affects other glands in the body, especially the adrenal gland, thyroid and liver.

POMC deficiency is inherited in families in a recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

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Affected populations

POMC deficiency is very rare, and it is unclear if it is more common in any particular populations. It has been diagnosed more often in populations where marriage between relatives is customary.

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POMC deficiency is diagnosed based on a clinical examination, symptoms and the results of laboratory and genetic testing. POMC deficiency is usually diagnosed after adrenal insufficiency is confirmed and obesity develops. The diagnosis of POMC deficiency is confirmed using genetic testing for variants in the POMC gene.

Because there are several inherited conditions that include excessive hunger and early-onset obesity, genetic testing may be done to help make a specific diagnosis. This testing often involves using a gene panel, allowing the lab to look for genetic changes in several different genes at the same time. Genetic testing is usually done with a blood or saliva sample. It is helpful to speak to a genetics professional before having genetic testing to learn more about the risk, benefits and limitations.

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Standard Therapies

Early treatment options for obesity for people with POMC deficiency include weight management through diet and behavioral counseling, physical training and outpatient obesity programs. However, most of these do not result in permanent weight loss.

Setmelanotide has been approved by the U.S. Food and Drug Administration (FDA) for people six years and older with obesity due to POMC deficiency which has been confirmed by genetic testing. This drug is given by daily injection. People taking setmelanotide are able to control their appetite, lose weight and maintain weight loss. Their skin and hair color may also get darker.

People with POMC deficiency also receive hydrocortisone to treat adrenal insufficiency and other medications to manage other symptoms of this condition.

People with POMC deficiency may be treated by a variety of different medical specialists, including gastroenterologists, nutritionists and endocrinologists. A psychologist or other mental health professional can help people cope with the symptoms of this condition.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Farooqi IS. Monogenic human obesity syndromes. Handb Clin Neurol. 2021; 181:301-310.

Gregoric N, Groselj U, Bratina N, Debeljak M, Zerjav Tansek M, Suput Omladic J, Kovac J, Battelino T, Kotnik P, Avbelj Stefanija M. Two cases with an early presented proopiomelanocortin deficiency-a long-term follow-up and systematic literature review. Front Endocrinol (Lausanne). 2021 Jun 9;12:689387.

Graves LE, Khouri JM, Kristidis P, Verge CF. Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases. J Paediatr Child Health. 2021 Apr;57(4):484-490. Epub 2021 Mar 5.

Markham A. Setmelanotide: First Approval. Drugs. 2021 Feb;81(3):397-403. doi: 10.1007/s40265-021-01470-9.

Ryan DH. Next generation antiobesity medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: what do they mean for clinical practice? J Obes Metab Syndr. 2021 Sep 30;30(3):196-208.

Yeo GSH, Chao DHM, Siegert AM, Koerperich ZM, Ericson MD, Simonds SE, Larson CM, Luquet S, Clarke I, Sharma S, Clément K, Cowley MA, Haskell-Luevano C, Van Der Ploeg L, Adan RAH. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy. Mol Metab. 2021 Jun;48:101206.  Epub 2021 Mar 6.

Clément K, Mosbah H, Poitou C. Rare genetic forms of obesity: From gene to therapy. Physiol Behav. 2020 Dec 1;227:113134. Epub 2020 Aug 14.

Ozsu E, Bahm A. Delayed diagnosis of proopiomelanocortin (POMC) deficiency with type 1 diabetes in a 9-year-old girl and her infant sibling. J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1137-1140.

Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severeearly-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998 Jun;19(2):155-7.


Setmelanotide Injection. MedlinePlus. Updated August 15, 2022. Available from: https://medlineplus.gov/druginfo/meds/a622059.html Accessed Jan 3, 2023.

Unexplained Childhood Obesity? Consider Genetic Causes. Children’s Doctor, CHOP. Dec 08, 2021. https://www.chop.edu/news/unexplained-childhood-obesity-consider-genetic-causes. Accessed Jan 9, 2023.

Obesity, Early-onset, with Adrenal Insufficiency and Red Hair; OBAIRH. Online Mendelian Inheritance in Man (OMIM). Last updated: February 22, 2018. Available from: https://www.omim.org/entry/609734 Accessed Jan 9, 2023.

Proopiomelanocortin deficiency. MedlinePlus. Last updated Feb 2014 Available from: https://medlineplus.gov/genetics/condition/proopiomelanocortin-deficiency/ Accessed Jan 9, 2023.

Obesity due to pro-opiomelanocortin deficiency. Orphanet. Last updated May 2007. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=71526 Accessed Jan 9, 2023.

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