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

LEPR Deficiency


Last updated: 2/21/2023
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


LEPR deficiency is a rare, inherited condition that affects how the body processes energy, responds to food and stores fat. Most people with this condition are obese before one year of age. Other symptoms include constant hunger and abnormal behaviors related to food. People affected with LEPR deficiency have low levels of sex hormones (hypogonadotropic hypogonadism) resulting in late or absent puberty and infertility. LEPR deficiency is caused by changes (mutations or variants) in the LEPR gene, which is responsible for making the receptor that interacts with a protein called leptin. Leptin is important for regulating appetite and growth of body fat. This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Diet, behavior modification, exercise programs and bariatric surgery have been used to help manage the symptoms of LEPR deficiency. Treatment is available for this condition using a drug called setmelanotide. With treatment, people with LEPR deficiency develop a normal appetite, lose weight and fat and can maintain the weight loss.


LEPR deficiency is rare, making it difficult to predict exactly how it will affect someone who is newly diagnosed with 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, morbid, due to leptin receptor deficiency
  • obesity due to leptin receptor gene deficiency
  • leptin receptor deficiency
  • LepR deficiency
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Signs & Symptoms

The symptoms of LEPR deficiency are different from person to person, with the most common symptom being early onset obesity. At birth, babies with LEPR deficiency have a normal weight. The earliest symptoms are constant hunger and excessive eating (hyperphagia) leading to rapid weight gain and obesity before one year of age. People with LEPR deficiency always feel hungry even after eating a full meal and often have abnormal behaviors related to food. Many have low levels of sex hormones (hypogonadotropic hypogonadism) causing delayed or absent puberty and infertility. Other symptoms may include low thyroid hormone and insulin resistance, which can lead to type 2 diabetes. Some children with LEPR deficiency get frequent infections because their immune system doesn’t work correctly. Excessive weight gain can lead to other symptoms such as abnormal bone growth, liver disease and difficultly walking.

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LEPR deficiency is caused by pathogenic variants (mutations) in the LEPR gene. The LEPR gene is responsible for making the leptin receptor, which works together with the protein, leptin. Leptin is made by fat cells and helps regulate energy storage in the body by balancing how much fat is made and how much is burned for energy. Without leptin receptors, leptin can’t do its job and the body doesn’t recognize when the body has enough energy and it’s time to stop eating.

LEPR 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

LEPR deficiency is a very rare disorder. In 2021, approximately 88 patients had been reported worldwide. It has been estimated that 1.34 per 1 million people may have this condition.

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LEPR deficiency is diagnosed based on a clinical examination, symptoms and the results of laboratory and genetic testing. 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 variants 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

Setmelanotide has been approved by the U.S. Food and Drug Administration (FDA) for people six years and older with obesity due to LEPR deficiency which has been diagnosed 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. People with LEPR 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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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.

Markham A. Setmelanotide: First Approval. Drugs. 2021 Feb;81(3):397-403.

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.

Kleinendorst L, Abawi O, van der Kamp HJ, Alders M, Meijers-Heijboer HEJ, van Rossum EFC, van den Akker ELT, van Haelst MM. Leptin receptor deficiency: a systematic literature review and prevalence estimation based on population genetics. Eur J Endocrinol. 2020 Jan;182(1):47-56.

Nunziata A, Funcke JB, Borck G, von Schnurbein J, Brandt S, Lennerz B, Moepps B, Gierschik P, Fischer-Posovszky P, Wabitsch M. Functional and Phenotypic Characteristics of Human Leptin Receptor Mutations. J Endocr Soc. 2018 Sep 17;3(1):27-41.

Dehghani, M. R., Mehrjardi, M. Y. V., Dilaver, N., Tajamolian, M., Enayati, S., Ebrahimi, P., Amoli, M. M., Farooqi, S., Maroofian, R. Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity. Europ. J. Med. Genet. 2018;61: 465-467.

Wasim M, Awan FR, Najam SS, Khan AR, Khan HN. Role of Leptin Deficiency, Inefficiency, and Leptin Receptors in Obesity. Biochem Genet. 2016 Oct;54(5):565-72. doi: 10.1007/s10528-016-9751-z. Epub 2016 Jun 16.


Leptin Receptor Deficiency; LEPRD, Online Mendelian Inheritance in Man (OMIM). MIM 614963. Last updated: 5/01/2019. Available from: https://www.omim.org/entry/614963 Accessed Jan 11, 2023.

Leptin Receptor Deficiency. MedlinePlus. Updated Jul 1, 2016. Available from: https://medlineplus.gov/genetics/condition/leptin-receptor-deficiency/ Accessed Jan 11, 2023.

Obesity due to leptin receptor gene deficiency. Orphanet. Last updated May 2007. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=179494 Accessed Jan 11, 2023.

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Programs & Resources

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Patient Organizations

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Powered by NORD, the IAMRARE Registry Platform® is driving transformative change in the study of rare disease. With input from doctors, researchers, and the US Food & Drug Administration, NORD has created IAMRARE to facilitate patient-powered natural history studies to shape rare disease research and treatments. The ultimate goal of IAMRARE is to unite patients and research communities in the improvement of care and drug development.

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