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Disease Profile

Obesity due to congenital leptin deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Obesity due to congenital leptin deficiency; Leptin deficiency or dysfunction; LEPD;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 66628

Definition
Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.

Epidemiology
It has been described in less than 30 patients.

Clinical description
Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. An increased susceptibility to infections has also been reported in these infants and appears to be associated with reduced numbers of circulating CD4+ T cells, and impaired T cell proliferation and cytokine release. Other features of the disorder include hyperinsulinaemia, advanced bone age, hypothalamic hypothyroidism and hypogonadotropic hypogonadism leading to a failure to undergo puberty.

Etiology
Leptin is an adipocyte-derived hormone that plays an important role in energy balance and appetite suppression. Whilst the majority of obese patients display hyperleptinaemia, patients with congenital leptin deficiency have undetectable levels of leptin in the serum. This absence of serum leptin is caused by homozygous frameshift or missense mutations in the ob gene (7q31.3) and is inherited as an autosomal recessive trait. However, a similar phenotype has been observed in three individuals from one consanguineous family who carried homozygous mutations in the gene encoding the leptin receptor (LEPR, 1p31).

Diagnostic methods
Family history, severe hyperphagia and early-onset obesity may lead to suspicion of a monogenic obesity syndrome. The diagnosis of congenital leptin deficiency can be confirmed by analysis of serum leptin levels or identification of mutations in the ob gene.

Management and treatment
Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia.

Prognosis
As a result, the prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Decreased serum leptin
0003292
Obesity
Having too much body fat
0001513
80%-99% of people have these symptoms
Absence of secondary sex characteristics
0008187
Decreased proportion of CD4-positive helper T cells
0005407
Decreased serum estradiol
0008214
Decreased serum testosterone level
Decreased serum testosterone levels
Low serum testosterone level
Low serum testosterone levels

[ more ]

0040171
Decreased T cell activation
0005419
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Gynecomastia
Enlarged male breast
0000771
Hypergonadotropic hypogonadism
0000815
Hyperinsulinemia
0000842
Hypoplasia of the ovary
Underdeveloped ovary
0008724
Polyphagia
Voracious appetite
0002591
Primary amenorrhea
0000786
30%-79% of people have these symptoms
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Insulin-resistant diabetes mellitus
Insulin resistant diabetes
Insulin-resistant diabetes

[ more ]

0000831
Orthostatic hypotension due to autonomic dysfunction
0004926
Pituitary hypothyroidism
Low thyroid gland function due to abnormal pituitary gland
0008245
Recurrent upper respiratory tract infections
Recurrent colds
0002788
Percent of people who have these symptoms is not available through HPO
Abnormal eating behavior
0100738
Autosomal recessive inheritance
0000007
Hypogonadism
Decreased activity of gonads
0000135
Micropenis
Short penis
Small penis

[ more ]

0000054
Recurrent ear infections
Frequent ear infections
0410018
Recurrent pneumonia
0006532

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.