U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Obesity due to congenital leptin deficiency(LEPD)

MedGen UID:
767138
Concept ID:
C3554224
Disease or Syndrome
Synonyms: Leptin Deficiency; Leptin deficiency or dysfunction
SNOMED CT: Congenital leptin deficiency (700150001); Obesity due to congenital leptin deficiency (700150001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LEP (7q32.1)
 
Monarch Initiative: MONDO:0013991
OMIM®: 614962
Orphanet: ORPHA66628

Definition

Leptin deficiency or dysfunction (LEPD) is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (Ozata et al., 1999). [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital leptin 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. Without treatment, the extreme hunger continues and 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 congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).  https://medlineplus.gov/genetics/condition/congenital-leptin-deficiency

Clinical features

From HPO
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Decreased testicular size
MedGen UID:
66027
Concept ID:
C0241355
Finding
Reduced volume of the testicle (the male gonad).
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent ear infections
MedGen UID:
473277
Concept ID:
C0743360
Finding
Increased susceptibility to ear infections, as manifested by recurrent episodes of ear infections.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Decreased serum leptin
MedGen UID:
373413
Concept ID:
C1837802
Finding
A decreased concentration of leptin in the blood.
Gynecomastia
MedGen UID:
6694
Concept ID:
C0018418
Disease or Syndrome
Abnormal development of large mammary glands in males resulting in breast enlargement.

Term Hierarchy

Follow this link to review classifications for Obesity due to congenital leptin deficiency in Orphanet.

Professional guidelines

PubMed

Araújo-Vilar D, Santini F
J Endocrinol Invest 2019 Jan;42(1):61-73. Epub 2018 Apr 27 doi: 10.1007/s40618-018-0887-z. PMID: 29704234Free PMC Article
Paz-Filho G, Mastronardi CA, Licinio J
Metabolism 2015 Jan;64(1):146-56. Epub 2014 Aug 3 doi: 10.1016/j.metabol.2014.07.014. PMID: 25156686
Bry-Gauillard H, Trabado S, Bouligand J, Sarfati J, Francou B, Salenave S, Chanson P, Brailly-Tabard S, Guiochon-Mantel A, Young J
Ann Endocrinol (Paris) 2010 May;71(3):158-62. Epub 2010 Apr 3 doi: 10.1016/j.ando.2010.02.024. PMID: 20363464

Recent clinical studies

Etiology

Rajcsanyi LS, Zheng Y, Fischer-Posovszky P, Wabitsch M, Hebebrand J, Hinney A
PLoS One 2022;17(9):e0266642. Epub 2022 Sep 19 doi: 10.1371/journal.pone.0266642. PMID: 36121795Free PMC Article
Puder L, Roth S, Krabusch P, Wiegand S, Opitz R, Bald M, Flück C, Schulz E, Voss E, Markó L, Linz P, Berger F, Müller DN, Kuehne T, Litt MJ, Cone RD, Kühnen P, Kelm M
J Clin Endocrinol Metab 2021 Aug 18;106(9):2606-2616. doi: 10.1210/clinem/dgab368. PMID: 34036349Free PMC Article
Yaghootkar H, Zhang Y, Spracklen CN, Karaderi T, Huang LO, Bradfield J, Schurmann C, Fine RS, Preuss MH, Kutalik Z, Wittemans LBL, Lu Y, Metz S, Willems SM, Li-Gao R, Grarup N, Wang S, Molnos S, Sandoval-Zárate AA, Nalls MA, Lange LA, Haesser J, Guo X, Lyytikäinen LP, Feitosa MF, Sitlani CM, Venturini C, Mahajan A, Kacprowski T, Wang CA, Chasman DI, Amin N, Broer L, Robertson N, Young KL, Allison M, Auer PL, Blüher M, Borja JB, Bork-Jensen J, Carrasquilla GD, Christofidou P, Demirkan A, Doege CA, Garcia ME, Graff M, Guo K, Hakonarson H, Hong J, Ida Chen YD, Jackson R, Jakupović H, Jousilahti P, Justice AE, Kähönen M, Kizer JR, Kriebel J, LeDuc CA, Li J, Lind L, Luan J, Mackey DA, Mangino M, Männistö S, Martin Carli JF, Medina-Gomez C, Mook-Kanamori DO, Morris AP, de Mutsert R, Nauck M, Prokic I, Pennell CE, Pradhan AD, Psaty BM, Raitakari OT, Scott RA, Skaaby T, Strauch K, Taylor KD, Teumer A, Uitterlinden AG, Wu Y, Yao J, Walker M, North KE, Kovacs P, Ikram MA, van Duijn CM, Ridker PM, Lye S, Homuth G, Ingelsson E, Spector TD, McKnight B, Province MA, Lehtimäki T, Adair LS, Rotter JI, Reiner AP, Wilson JG, Harris TB, Ripatti S, Grallert H, Meigs JB, Salomaa V, Hansen T, Willems van Dijk K, Wareham NJ, Grant SFA, Langenberg C, Frayling TM, Lindgren CM, Mohlke KL, Leibel RL, Loos RJF, Kilpeläinen TO
Diabetes 2020 Dec;69(12):2806-2818. Epub 2020 Sep 11 doi: 10.2337/db20-0070. PMID: 32917775Free PMC Article
Kim MS, Ryabets-Lienhard A, Dao-Tran A, Mittelman SD, Gilsanz V, Schrager SM, Geffner ME
J Clin Endocrinol Metab 2015 Aug;100(8):E1153-9. Epub 2015 Jun 10 doi: 10.1210/jc.2014-4033. PMID: 26062016Free PMC Article
Völkl TM, Simm D, Beier C, Dörr HG
Pediatrics 2006 Jan;117(1):e98-105. doi: 10.1542/peds.2005-1005. PMID: 16396852

Diagnosis

Altarejos JY, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert AH, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim JH, Stevis P, Huang T, Zambrowicz B, Olson WC, Godin S, Bradley E, Gewitz AD, Baker M, Hench R, Davenport MS, Chenevert TL, DiPaola F, Yancopoulos GD, Murphy AJ, Herman GA, Musser BJ, Dansky H, Harp J, Gromada J, Sleeman MW, Oral EA, Olenchock BA
Sci Transl Med 2023 Nov 22;15(723):eadd4897. doi: 10.1126/scitranslmed.add4897. PMID: 37992152
Puder L, Roth S, Krabusch P, Wiegand S, Opitz R, Bald M, Flück C, Schulz E, Voss E, Markó L, Linz P, Berger F, Müller DN, Kuehne T, Litt MJ, Cone RD, Kühnen P, Kelm M
J Clin Endocrinol Metab 2021 Aug 18;106(9):2606-2616. doi: 10.1210/clinem/dgab368. PMID: 34036349Free PMC Article
Araújo-Vilar D, Santini F
J Endocrinol Invest 2019 Jan;42(1):61-73. Epub 2018 Apr 27 doi: 10.1007/s40618-018-0887-z. PMID: 29704234Free PMC Article
Kim MS, Ryabets-Lienhard A, Dao-Tran A, Mittelman SD, Gilsanz V, Schrager SM, Geffner ME
J Clin Endocrinol Metab 2015 Aug;100(8):E1153-9. Epub 2015 Jun 10 doi: 10.1210/jc.2014-4033. PMID: 26062016Free PMC Article
Bry-Gauillard H, Trabado S, Bouligand J, Sarfati J, Francou B, Salenave S, Chanson P, Brailly-Tabard S, Guiochon-Mantel A, Young J
Ann Endocrinol (Paris) 2010 May;71(3):158-62. Epub 2010 Apr 3 doi: 10.1016/j.ando.2010.02.024. PMID: 20363464

Therapy

Altarejos JY, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert AH, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim JH, Stevis P, Huang T, Zambrowicz B, Olson WC, Godin S, Bradley E, Gewitz AD, Baker M, Hench R, Davenport MS, Chenevert TL, DiPaola F, Yancopoulos GD, Murphy AJ, Herman GA, Musser BJ, Dansky H, Harp J, Gromada J, Sleeman MW, Oral EA, Olenchock BA
Sci Transl Med 2023 Nov 22;15(723):eadd4897. doi: 10.1126/scitranslmed.add4897. PMID: 37992152
Araújo-Vilar D, Santini F
J Endocrinol Invest 2019 Jan;42(1):61-73. Epub 2018 Apr 27 doi: 10.1007/s40618-018-0887-z. PMID: 29704234Free PMC Article
Wasim M, Awan FR, Najam SS, Khan AR, Khan HN
Biochem Genet 2016 Oct;54(5):565-72. Epub 2016 Jun 16 doi: 10.1007/s10528-016-9751-z. PMID: 27313173
Tchang BG, Shukla AP, Aronne LJ
Expert Opin Biol Ther 2015 Jul;15(7):1061-75. doi: 10.1517/14712598.2015.1052789. PMID: 26063386
Völkl TM, Simm D, Beier C, Dörr HG
Pediatrics 2006 Jan;117(1):e98-105. doi: 10.1542/peds.2005-1005. PMID: 16396852

Prognosis

Rajcsanyi LS, Zheng Y, Fischer-Posovszky P, Wabitsch M, Hebebrand J, Hinney A
PLoS One 2022;17(9):e0266642. Epub 2022 Sep 19 doi: 10.1371/journal.pone.0266642. PMID: 36121795Free PMC Article
Cagliyan E, Ozmen S, Timur HT, Ozgozen ME, Semiz GG
J Obstet Gynaecol Res 2022 Nov;48(11):2964-2967. Epub 2022 Jul 31 doi: 10.1111/jog.15379. PMID: 35909242
Ozsu E, Ceylaner S, Onay H
J Pediatr Endocrinol Metab 2017 Oct 26;30(11):1227-1230. doi: 10.1515/jpem-2017-0063. PMID: 29040067
Blüher M, Mantzoros CS
Metabolism 2015 Jan;64(1):131-45. Epub 2014 Oct 23 doi: 10.1016/j.metabol.2014.10.016. PMID: 25497344
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
N Engl J Med 2007 Jan 18;356(3):237-47. doi: 10.1056/NEJMoa063988. PMID: 17229951Free PMC Article

Clinical prediction guides

Rajcsanyi LS, Zheng Y, Fischer-Posovszky P, Wabitsch M, Hebebrand J, Hinney A
PLoS One 2022;17(9):e0266642. Epub 2022 Sep 19 doi: 10.1371/journal.pone.0266642. PMID: 36121795Free PMC Article
Santos JL, Cortés VA
Obes Rev 2021 Jan;22(1):e13114. Epub 2020 Aug 2 doi: 10.1111/obr.13114. PMID: 33030294
Paz-Filho G, Mastronardi CA, Licinio J
Metabolism 2015 Jan;64(1):146-56. Epub 2014 Aug 3 doi: 10.1016/j.metabol.2014.07.014. PMID: 25156686
Blüher S, Shah S, Mantzoros CS
J Investig Med 2009 Oct;57(7):784-8. doi: 10.2310/JIM.0b013e3181b9163d. PMID: 19730134Free PMC Article
Farooqi IS, O'Rahilly S
Am J Clin Nutr 2009 Mar;89(3):980S-984S. Epub 2009 Feb 11 doi: 10.3945/ajcn.2008.26788C. PMID: 19211814

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...