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Genetics Home Reference: your guide to understanding genetic conditions
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Leptin receptor deficiency

Reviewed October 2013

What is leptin receptor deficiency?

Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.

People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).

How common is leptin receptor deficiency?

The prevalence of leptin receptor deficiency is unknown. It has been estimated to account for up to 3 percent of individuals with severe obesity and hyperphagia that begins in early childhood.

What genes are related to leptin receptor deficiency?

Leptin receptor deficiency is caused by mutations in the LEPR gene. This gene provides instructions for making a protein called the leptin receptor, which is involved in the regulation of body weight. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body including a part of the brain called the hypothalamus. The hypothalamus controls hunger and thirst as well as other functions such as sleep, moods, and body temperature. It also regulates the release of many hormones that have functions throughout the body.

The leptin receptor is turned on (activated) by a hormone called leptin that attaches (binds) to the receptor, fitting into it like a key into a lock. Normally, the body's fat cells release leptin in proportion to their size. As fat cells become larger, they produce more leptin. This rise in leptin indicates that fat stores are increasing. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect hunger and help produce a feeling of fullness (satiety).

LEPR gene mutations that cause leptin receptor deficiency prevent the receptor from responding to leptin, leading to the excessive hunger and weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency, researchers suggest that leptin receptor signaling is also involved in regulating the body's response to hormones that control sexual development, and that this response is affected by LEPR gene mutations. However, the mechanism of this effect is unknown.

Leptin receptor deficiency is a rare cause of obesity. Researchers are studying the factors involved in more common forms of obesity.

Related Gene(s)

Changes in this gene are associated with leptin receptor deficiency.

  • LEPR

How do people inherit leptin receptor deficiency?

This condition 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 an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

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

These resources address the diagnosis or management of leptin receptor 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)
  • Genetics of Obesity Study (http://www.goos.org.uk/home)
  • Genetic Testing Registry: Leptin receptor deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN120495)
  • National Heart, Lung, and Blood Institute: How Are Overweight and Obesity Treated? (http://www.nhlbi.nih.gov/health/health-topics/topics/obe/treatment.html)

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

You may find the following resources about leptin receptor 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 leptin receptor deficiency?

  • congenital deficiency of the leptin receptor
  • leptin receptor-related monogenic obesity
  • obesity due to leptin receptor gene deficiency
  • obesity, morbid, due to leptin receptor deficiency
  • obesity, morbid, nonsyndromic 2

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 leptin receptor deficiency?

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

What glossary definitions help with understanding leptin receptor deficiency?

autosomal ; autosomal recessive ; cell ; chronic ; congenital ; deficiency ; excessive eating ; fat cells ; gene ; hormone ; hyperphagia ; hypogonadism ; hypogonadotropic ; hypothalamus ; infertile ; inherited ; monogenic ; prevalence ; protein ; puberty ; receptor ; recessive ; satiety

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

References

  • Andiran N, Celik N, Andiran F. Homozygosity for two missense mutations in the leptin receptor gene (P316:W646C) in a Turkmenian girl with severe early-onset obesity. J Pediatr Endocrinol Metab. 2011;24(11-12):1043-5. (http://www.ncbi.nlm.nih.gov/pubmed/22308862?dopt=Abstract)
  • Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougnères P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998 Mar 26;392(6674):398-401. (http://www.ncbi.nlm.nih.gov/pubmed/9537324?dopt=Abstract)
  • Dubern B, Clement K. Leptin and leptin receptor-related monogenic obesity. Biochimie. 2012 Oct;94(10):2111-5. doi: 10.1016/j.biochi.2012.05.010. Epub 2012 May 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22627381?dopt=Abstract)
  • Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, Lank E, Bottomley B, Lopez-Fernandez J, Ferraz-Amaro I, Dattani MT, Ercan O, Myhre AG, Retterstol L, Stanhope R, Edge JA, McKenzie S, Lessan N, Ghodsi M, De Rosa V, Perna F, Fontana S, Barroso I, Undlien DE, O'Rahilly S. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med. 2007 Jan 18;356(3):237-47. (http://www.ncbi.nlm.nih.gov/pubmed/17229951?dopt=Abstract)
  • Kimber W, Peelman F, Prieur X, Wangensteen T, O'Rahilly S, Tavernier J, Farooqi IS. Functional characterization of naturally occurring pathogenic mutations in the human leptin receptor. Endocrinology. 2008 Dec;149(12):6043-52. doi: 10.1210/en.2008-0544. Epub 2008 Aug 14. (http://www.ncbi.nlm.nih.gov/pubmed/18703626?dopt=Abstract)
  • Mazen I, El-Gammal M, Abdel-Hamid M, Farooqi IS, Amr K. Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity. Mol Genet Metab. 2011 Apr;102(4):461-4. doi: 10.1016/j.ymgme.2010.12.013. Epub 2010 Dec 31. (http://www.ncbi.nlm.nih.gov/pubmed/21306929?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: October 2013
Published: November 24, 2014