NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Proopiomelanocortin Deficiency

Synonym: POMC Deficiency

, BSc, MPhil, PhD, MRCP(UK) and , BSc, MBBS, PhD, FRCP.

Author Information

Initial Posting: .

Summary

Clinical characteristics.

Proopiomelanocortin (POMC) deficiency is characterized by severe, early-onset hyperphagic obesity and congenital adrenal insufficiency, the latter secondary to corticotropin (ACTH) deficiency. In the first months of life most children with POMC deficiency experience exponential weight gain, hyperphagia, cholestasis, and adrenal insufficiency. Weight gain continues rapidly, so that by the end of the first year of life obesity is severe (i.e., weight well above the 98th centile for age, without increased height). Red hair and Fitzpatrick type 1 skin (which always burns and never tans) are common, but not invariably present. On occasion central hypothyroidism (resulting from thyroid stimulating hormone [TSH] deficiency), adolescent-onset growth hormone (GH) deficiency, and adolescent-onset hypogonadotropic hypogonadism resulting from deficiency of luteinizing hormone (LH) and follicule stimulating hormone (FSH) can be observed.

Diagnosis/testing.

The diagnosis of POMC deficiency is confirmed by the presence of biallelic POMC pathogenic variants.

Management.

Treatment of manifestations: Neonatal adrenal insufficiency is treated in the usual manner with hydrocortisone replacement therapy. No effective medical therapy for hyperphagic obesity is known; thus, lifestyle measures are necessary to control weight gain. Skin care relies on avoiding sun exposure in the middle four hours of the day (i.e., 10 am – 2 pm), cover-up clothing, and high-factor sunscreen. Hypothyroidism is treated in the usual manner with levothyroxine; however, it is important to note that thyroid hormone replacement therapy should not begin until adrenal function has been evaluated and adrenal insufficiency (if present) has been treated. GH deficiency and hypogonadotropic hypogonadism are treated in the usual manner.

Prevention of primary manifestations: Prompt treatment of ACTH, TSH, GH, LH, and FSH deficiency prevents the consequences of these hormone deficiencies.

Surveillance: From the time of diagnosis, annual monitoring for deficiencies of TSH, GH, LH, and FSH. Surveillance of skin for premalignant lesions may be necessary depending on latitude and history of sun exposure. Malignant skin lesions have not specifically been reported to be associated with POMC deficiency, though a theoretic risk is assumed to exist.

Evaluation of relatives at risk: If the POMC pathogenic variants in the family are known, prenatal testing can clarify the genetic status of at-risk pregnancies so that glucocorticoid therapy can be initiated as soon as possible after birth in those infants known to have POMC deficiency.

If POMC deficiency has been previously diagnosed in a family and if the POMC pathogenic variants in the family are not known or if prenatal testing has not been performed, it is necessary to evaluate any at-risk newborns (e.g., sibs of a proband) for evidence of adrenal insufficiency and to initiate glucocorticoid therapy as soon as possible.

Genetic counseling.

POMC deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the POMC pathogenic variants have been identified in an affected family member.

Diagnosis

There are no formal diagnostic criteria for proopiomelanocortin (POMC) deficiency.

The diagnosis of POMC deficiency is suspected in a proband with the following clinical and laboratory findings:

  • Severe, hyperphagic obesity of onset in infancy
  • Congenital adrenal insufficiency, resulting from corticotropin (ACTH) deficiency

The diagnosis of POMC deficiency in a proband may also be supported by the following clinical and laboratory findings:

  • Very fair skin (Fitzpatrick skin type 1) which will never tan and always burns [Roberts 2009]
  • Red hair
  • Positive family history of obesity in sibs or other relatives who could share two pathogenic alleles with the proband
  • Central hypothyroidism (triodothyronine, tetraiodothyronine and thyrotropin, or TSH deficiency)
  • Growth hormone (GH) deficiency in later childhood or adolescence
  • Hypogonadotropic hypogonadism (deficiency of the gonadotropins LH and FSH)

The diagnosis of POMC deficiency is confirmed by the presence of biallelic POMC pathogenic variants (see Table 1).

Table 1.

Molecular Genetic Testing Used in Proopiomelanocortin Deficiency

Gene 1Test MethodVariants Detected 2Pathogenic Variant Detection Frequency by Test Method 3
POMCSequence analysis 4Sequence variantsUnknown
Deletion/duplication analysis 5Exon or whole-gene deletions or duplicationsUnknown, none reported 6
1.
2.

See Molecular Genetics for information on allelic variants.

3.

The ability of the test method used to detect a pathogenic variant that is present in the indicated gene

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

5.

Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

6.

No deletions or duplications of POMC have been reported to cause proopiomelanocortin deficiency. (Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic DNA.)

Clinical Characteristics

Clinical Description

In the first months of life most children with proopiomelanocortin (POMC) deficiency experience exponential weight gain, hyperphagia, cholestasis, and adrenal insufficiency. Weight gain continues rapidly, so that by the end of the first year of life obesity is severe (i.e., weight well above the 98th centile for age without increased height).

Red hair and Fitzpatrick type 1 skin (which always burns and never tans) are common, but not invariably present.

Krude et al [1998] reported the first two children with POMC deficiency, one of whom was a girl age three years. Both had adrenal insufficiency, severe obesity, and red hair.

Krude et al [2003] reported three additional unrelated European children with POMC deficiency who had congenital adrenal insufficiency, severe early onset obesity, and red hair; two had mild central hypothyroidism.

Farooqi et al [2006] described a child of Turkish origin with severe obesity and hypoadrenalism but without red hair.

Clément et al [2008] described an individual of North African ancestry. In addition to hypoadrenalism, obesity, and central hypothyroidism, the patient developed growth hormone (GH) and gonadotropin deficiency at the onset of puberty. Clinically, the patient did not have abnormal pigmentation; however, chemical analysis of hair pigment revealed increased production of pheomelanin and eumelanin compared with unaffected relatives.

Mendiratta et al [2011] reported a Hispanic girl age 18 months with congenital adrenal insufficiency (presenting with hypoglycemia at age 9 months) and severe obesity due to homozygosity for a pathogenic POMC variant that results in a premature termination codon. She did not have the typical pigmentary phenotype; detailed analysis of hair pigment was not described.

Cirillo et al [2012] described a boy age three years of North African ancestry who experienced hypoglycemia in the first days of life and was diagnosed with ACTH deficiency at age nine months, by which time he had developed severe obesity which worsened during the second and third years of life. Although he had dark brown to black hair, hair pigment analysis revealed significantly increased levels of pheomelanin and minimally reduced eumelanin when compared with other family members.

Aslan et al [2014] reported an individual who was homozygous for a rare variant upstream of the POMC coding sequence that abolished gene transcription. This patient also had type 1 diabetes mellitus with normal insulin requirements.

Pathogenesis

The phenotypic consequences of POMC deficiency (including adrenal insufficiency, altered pigmentation, and severe obesity) result from reduced or absent melanocortin signaling in target tissues. For example:

  • Impaired ACTH signaling through the MC2R in the adrenal cortex results in hypoadrenalism (i.e., absence of adrenal steroidogenesis).
  • Absence of α-MSH induced activation of MC1R in skin melanocytes results in the red hair and pale skin observed in some affected individuals.
  • Reduced activation of MC3- and MC4R proteins in the hypothalamic nuclei that regulate energy homeostasis causes severe early-onset obesity, in a manner similar to the severe early-onset obesity observed in children with deficiency of the MC4R protein itself.

Genotype-Phenotype Correlations

Large numbers of pathogenic variants (see Table 2) lead to the full phenotype as described in Clinical Description.

However, a number of individuals described have a single (i.e., heterozygous) base-pair pathogenic variant in a critical site, leading to severe, early-onset obesity without adrenal insufficiency or hypopigmentation [Challis et al 2002, Lee et al 2006, Dubern et al 2008].

Nomenclature

Proopiomelanocortin (POMC) was previously called proopiocortin (POC).

Prevalence

POMC is an extremely rare disease. Fewer than 50 affected individuals have been reported in the world literature.

There is no known increased prevalence in any particular ethnic group or geographic location.

Differential Diagnosis

Prohormone convertase-1 (PC-1) deficiency (OMIM 600955) mimics the obesity and adrenal failure of classic POMC deficiency; however, in addition, PC-1 deficiency is characterized by multiple other endocrinopathies and, in some instances, small-intestine dysfunction resulting in severe diarrhea and malabsorption.

Melanocortin-1 receptor (MC1R) deficiency (OMIM 155555) has a common genetic variant in the population (particularly in European populations) that is associated with red hair. This common variant could easily be co-inherited with another rarer disorder leading to early-onset obesity.

Beckwith-Wiedemann syndrome presents with high birth weight and neonatal hypoglycemia. Postnatal hyperphagia is not typically associated with BWS.

The following are all causes of childhood-onset obesity:

Table 2.

Monogenic Obesity Syndromes

Monogenic Obesity SyndromeGene(s) or Chromosome(s) Involved 1OMIM
Autosomal dominant
Brain-derived neurotrophic factor (BDNF) deficiencyBDNF113505
Melanocortin-4 receptor deficiencyMC4R155541
Rubinstein-Taybi syndromeCREBBP, EP300180849; 613684
TrkB deficiencyNTRK2613886
Ulnar-mammary syndromeTBX3181450
Autosomal recessive
Alström syndromeALMS1203800
Bardet-Biedl syndromeBBS1-16, ARL6, MKKS, MKS1, CEP290209900
Carpenter syndromeRAB23201000; 614976
Cohen syndromeVPS13B216550
Leptin deficiencyLEP614962
Leptin receptor deficiencyLEPR614963
Macrosomia, obesity, macrocephaly, and ocular abnormalities (MOMO) syndromeUnknown; AR inheritance unconfirmed157980
Majewski osteodysplastic primordial dwarfism type IIPCNT210720
Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM) syndromeINPP5E610156
Prohormone convertase 1/3 deficiencyPCSK1600955
SIM1 deficiencySIM1601665
X-linked
Börjeson-Forssman-Lehman syndromePHF6301900
Coffin–Lowry syndromeRPS6KA3303600
Fragile X syndromeFMR1300624
Chromosome defect
Diploid/triploid mosaicismDiploid/triploid mosaicism
Mental retardation, obesity, mandibular prognathism, and eye and skin anomalies (MOMES) syndromedel4q35.1, dup5p14.3606772
Microdeletion
16p11.2 microdeletion (SH2B deficiency)SH2B613444
Imprinted gene/region
Albright hereditary osteodystrophy (pseudohypoparathyroidism)GNAS103580
Prader-Willi syndromePWS region15q11-q13 (SNRPN, NDN, MAGEL2)176270
1.

Chromosome locus included when gene is unknown

The following inherited disorders of glucocorticoid metabolism leading to adrenal failure need consideration, as they could be inherited in association with non-syndromic obesity:

  • Melanocortin-2 receptor deficiency (OMIM 202200)
  • Melanocortin 2 receptor accessory protein (MRAP) deficiency (OMIM 607398)
  • Steroidogenic acute regulatory protein (STAR) deficiency (OMIM 201710)
  • Nicotinamide nucleotide transhydrogenase (NNT) deficiency (OMIM 614736)
  • Autoimmune polyendocrine syndrome, type 1 (OMIM 240300)
  • Natural killer cell and glucocorticoid deficiency with DNA repair defect (OMIM 609981)
  • Combined pituitary hormone deficiency, type 1 and type 2

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with proopiomelanocortin (POMC) deficiency, the following evaluations are recommended:

  • For adrenal insufficiency as a result of ACTH deficiency: 9 am plasma cortisol; plasma ACTH concentration; ACTH stimulation test
  • For central hypothyroidism: TRH test, serum TSH, total T4
  • For adolescent-onset growth hormone (GH) deficiency: insulin tolerance test and serum IGF-1 levels
  • For adolescent-onset hypogonadism: FSH, LH, testosterone and/or estradiol
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

The main treatment for POMC deficiency is hormone replacement therapy with glucocorticoids with other hormones as required, as well as skin care in the sun.

Adrenal insufficiency. Adrenal insufficiency is treated in the usual manner with hydrocortisone replacement therapy. Care by a pediatric endocrinologist is recommended.

Severe obesity. Hyperphagic obesity is recognized in the neonatal period and persists into adolescence and adulthood. At present, there is no recognized effective medical therapy to prevent weight gain; therefore, lifestyle measures should be instigated.

Fair skin. The individual may need appropriate verbal and written sun care advice (avoidance of sun exposure in the middle 4 hours of the day [i.e., 10 am - 2 pm], cover-up clothing, high-factor sunscreen). Discussion about the potential lifelong risk for skin cancer is recommended.

Hypothyroidism. The mild central hypothyroidism reported in POMC deficiency is treated with levothyroxine. Importantly, thyroid hormone replacement should not be initiated until adrenal function has been evaluated and adrenal insufficiency (if present) has been treated. Care by a pediatric endocrinologist is recommended.

Growth hormone (GH) deficiency. Adolescent-onset GH deficiency (a rare manifestation of POMC deficiency) is treated with daily subcutaneous GH injections. Care by a pediatric endocrinologist is recommended.

Hypogonadotropic hypogonadism. Adolescent-onset hypogonadism (a rare manifestation of POMC deficiency) can be treated with sex hormone replacement. Care by an endocrinologist experienced in treating this disorder is recommended.

Prevention of Primary Manifestations

Prompt treatment of ACTH, TSH, GH, LH, and FSH deficiency prevents the consequences of these hormone deficiencies.

Surveillance

From the time of diagnosis, annual monitoring for deficiencies of TSH, GH, LH, and FSH is indicated.

Surveillance of skin for premalignant lesions may be necessary depending on latitude and history of sun exposure. Malignant skin lesions have not specifically been reported to be associated with POMC deficiency, though a theoretic risk is assumed to exist.

Evaluation of Relatives at Risk

If the pathogenic variants in the family are known, prenatal testing can clarify the genetic status of at-risk pregnancies so that glucocorticoid therapy can be initiated as soon as possible after birth in those newborns known to have POMC deficiency.

If POMC deficiency has been previously diagnosed in a family member, and if the pathogenic variants in the family are not known or if prenatal testing has not been performed, it is necessary to evaluate any at-risk newborn (e.g., sibs of a proband) for evidence of adrenal insufficiency and to initiate glucocorticoid therapy as soon as possible if adrenal insufficiency is found.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Proopiomelanocortin (POMC) deficiency is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing adrenal insufficiency; however, a predisposition to obesity is conferred.

Offspring of a proband

  • It is unknown whether fertility is reduced in individuals with POMC deficiency.
  • The offspring of an individual with POMC deficiency are obligate heterozygotes (carriers) for a POMC pathogenic variant.

Other family members

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives is possible if the POMC pathogenic variants in an affected family member have been identified.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for POMC deficiency are possible.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • National Adrenal Diseases Foundation (NADF)
    505 Northern Boulevard
    Great Neck NY 11021
    Phone: 516-487-4992
    Email: nadfmail@aol.com

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Proopiomelanocortin Deficiency: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
POMC2p23​.3Pro-opiomelanocortinPOMC databasePOMCPOMC

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Proopiomelanocortin Deficiency (View All in OMIM)

176830PROOPIOMELANOCORTIN; POMC
609734OBESITY, EARLY-ONSET, WITH ADRENAL INSUFFICIENCY AND RED HAIR; OBAIRH

Gene structure. POMC comprises three exons of 406, 102, and 838 bp and spans approximately 7.8 kb. The predominant transcript is 1426 bp nucleotides long and encodes for a 267-amino acid polypeptide.

Pathogenic variants. Krude et al [1998] reported the first cases of human POMC deficiency in two children:

Krude et al [2003] reported three additional unrelated European children with POMC deficiency who were either compound heterozygous (c.[6851A>T] + [6996del]; c.[3804C>A] + [7100insGG]) or homozygous (c.3804C>A) for POMC pathogenic variants.

Farooqi et al [2006] described a homozygous pathogenic frame shift variant (c.6906Cdel) in POMC in a child of Turkish background.

Clément et al [2008] described a novel homozygous variant (c.6922insC) that impaired the production of all POMC-derived peptides in an individual of North African ancestry.

Mendiratta et al [2011] reported a novel homozygous nonsense variant (c.231C>A) in a Hispanic girl age 18 months.

Cirillo et al [2012] described a novel homozygous nonsense variant (c.202C>T) in a boy age three years of North African ancestry.

Aslan et al [2014] described a novel homozygous variant in the 5' untranslated region (-11C>A) of POMC in an individual with POMC deficiency and coincidental type 1 diabetes mellitus. Functional studies of this variant showed that it strongly attenuated transcription of POMC.

See Table 3 (pdf) for a list of pathogenic variants discussed in this section.

Table 4.

POMC Genotypes Detected in Affected Individuals

Variants DetectedReferences
c.7013G>T, c.7133delC compound heterozygote (n=1)Krude et al [1998]
c.3804C>A homozygote (n=2)Krude et al [1998], Krude et al [2003]
c.6851A>T, 6996del compound heterozygote (n=1)Krude et al [2003]
c.3804C>A + 7100insGG compound heterozygote (n=1)Krude et al [2003]
c.6906Cdel homozygote (n=1)Farooqi et al [2006]
c.6922InsC homozygote (n=1)Clément et al [2008]
c.231C>A homozygote (n=1)Mendiratta et al [2011]
c.202C>T homozygote (n=1)Cirillo et al [2012]
-11C>A homozygote (n=1)Aslan et al [2014]

Normal gene product. The product of POMC is proopiomelanocortin, a complex polypeptide that is post-translationally processed by endoproteases in a tissue specific manner to produce a number of biologically active peptides. These include corticotropin (ACTH), β-endorphin, and α-, β- and γ-melanocyte stimulating hormone (MSH) which are implicated in a number of physiologic actions including energy homeostasis, adrenal steroidogenesis, and hair pigmentation. The biologic actions of melanocortin peptides are mediated by the melanocortin receptors (MC1R-MC5R), members of the G-protein coupled receptor family.

Abnormal gene product. The phenotypic consequences of POMC deficiency - including adrenal insufficiency, altered pigmentation, and severe obesity - result from an absence of melanocortin signaling in target tissues. For example, hypoadrenalism due to an absence of adrenal steroidogenesis results from impaired ACTH signaling through the MC2R in the adrenal cortex, whereas an absence of α-MSH induced activation of MC1R in skin melanocytes results in the red hair and pale skin observed in some affected individuals. Severe early-onset obesity is caused by reduced activation of MC3- and MC4R in hypothalamic nuclei that regulate energy homeostasis. The importance of hypothalamic melanocortin signaling in the regulation of body weight is emphasised by the observation that human MC4R deficiency also results in severe obesity in children.

References

Literature Cited

  • Aslan IR, Ranadive SA, Valle I, Kollipara S, Noble JA, Vaisse C. The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus. Int J Obes (Lond). 2014;38:148–51. [PMC free article: PMC4648369] [PubMed: 23649472]
  • Challis BG, Pritchard LE, Creemers JWM, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GSH, Bhattacharyya S, Froguel P, White A, Farooqi IS, O’Rahilly S. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Human Molecular Genetics. 2002;11:1997–2004. [PubMed: 12165561]
  • Cirillo G, Marini R, Ito S, Wakamatsu K, Scianguetta S, Bizzarri C, Romano A, Grandone A, Perrone L, Cappa M, Miraglia Del Giudice E. Lack of red hair phenotype in a North-African obese child homozygous for a novel POMC null mutation: nonsense-mediated decay RNA evaluation and hair pigment chemical analysis. Br J Dermatol. 2012;167:1393–5. [PubMed: 22612534]
  • Clément K, Dubern B, Mencarelli M, Czernichow P, Ito S, Wakamatsu K, Barsh GS, Vaisse C, Leger J. Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene. J Clin Endocrinol Metab. 2008;93:4955–62. [PMC free article: PMC2729235] [PubMed: 18765507]
  • Dubern B, Lubrano-Berthelier C, Mencarelli M, Ersoy B, Frelut ML, Bouglé D, Costes B, Simon C, Tounian P, Vaisse C, Clément K. Mutational analysis of the pro-opiomelanocortin gene in French obese children led to the identification of a novel deleterious heterozygous mutation located in the alpha-melanocyte stimulating hormone domain. Pediatr Res. 2008;63:211–6. [PubMed: 18091355]
  • Farooqi IS, Drop S, Clements A, Keogh JM, Biernacka J, Lowenbein S, Challis BG, O'Rahilly S. Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes. 2006;55:2549–53. [PubMed: 16936203]
  • Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19:155–7. [PubMed: 9620771]
  • Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, Grüters A. Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab. 2003;88:4633–40. [PubMed: 14557433]
  • Lee YS, Challis BG, Thompson DA, Yeo GS, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CC, Wareham NJ, Froguel P, Millhauser GL, O'Rahilly S, Farooqi IS. A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab. 2006;3:135–40. [PubMed: 16459314]
  • Mendiratta MS, Yang Y, Balazs AE, Willis AS, Eng CM, Karaviti LP, Potocki L. Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation. Int J Pediatr Endocrinol. 2011:5. [PMC free article: PMC3159139] [PubMed: 21860632]
  • Roberts WE. Skin type classification systems old and new. Dermatol Clin. 2009;27:529–33. [PubMed: 19850202]

Suggested Reading

  • Baker M, Gaukrodger N, Mayosi BM, Imrie H, Farrall M, Watkins H, Connell JM, Avery PJ, Keavney B. Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Diabetes. 2005;54:2492–6. [PubMed: 16046320]
  • Buono P, Pasanisi F, Nardelli C, Ieno L, Capone S, Liguori R, Finelli C, Oriani G, Contaldo F, Sacchetti L. Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy. Clin Chem. 2005;51:1358–64. [PubMed: 15951321]
  • Chen Y, Snieder H, Wang X, Kaviya B, McCaffrey C, Spector TD, Carter ND, O'Dell SD. Proopiomelanocortin gene variants are associated with serum leptin and body fat in a normal female population. Eur J Hum Genet. 2005;13:772–80. [PubMed: 15812563]
  • Coll AP, Farooqi IS, Challis BG, Yeo GS, O'Rahilly S. Proopiomelanocortin and energy balance: insights from human and murine genetics. J Clin Endocrinol Metab. 2004;89:2557–62. [PubMed: 15181023]
  • Creemers JW, Lee YS, Oliver RL, Bahceci M, Tuzcu A, Gokalp D, Keogh J, Herber S, White A, O'Rahilly S, Farooqi IS. Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway. J Clin Endocrinol Metab. 2008;93:4494–9. [PubMed: 18697863]
  • Dubern B, Clément K, Pelloux V, Froguel P, Girardet JP, Guy-Grand B, Tounian P. Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J Pediatr. 2001;139:204–9. [PubMed: 11487744]
  • Echwald SM, Sørensen TI, Andersen T, Tybjaerg-Hansen A, Clausen JO, Pedersen O. Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity. Int J Obes Relat Metab Disord. 1999;23:293–8. [PubMed: 10193875]
  • Hixson JE, Almasy L, Cole S, Birnbaum S, Mitchell BD, Mahaney MC, Stern MP, MacCluer JW, Blangero J, Comuzzie AG. Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC. J Clin Endocrinol Metab. 1999;84:3187–91. [PubMed: 10487685]
  • Hung CN, Poon WT, Lee CY, Law CY, Chan AY. A case of early-onset obesity, hypocortisolism, and skin pigmentation problem due to a novel homozygous mutation in the proopiomelanocortin (POMC) gene in an Indian boy. J Pediatr Endocrinol Metab. 2012;25:175–9. [PubMed: 22570972]
  • Mencarelli M, Zulian A, Cancello R, Alberti L, Gilardini L, Di Blasio AM, Invitti C. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity. Eur J Hum Genet. 2012;20:1290–4. [PMC free article: PMC3499745] [PubMed: 22643178]
  • Millington GWM. Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors. Clin Exp Dermatol. 2006;31:407–12. [PubMed: 16681590]
  • Millington GWM. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab (Lond). 2007;4:18. [PMC free article: PMC2018708] [PubMed: 17764572]
  • Millington GWM. Obesity, genetics and the skin. Clin Exp Dermatol. 2013;38:50–6. [PubMed: 23252752]
  • Ohshiro Y, Ueda K, Wakasaki H, Kosaka M, Nishi M, Sasaki H, Takasu N, Nanjo K. Sequence analysis of the pro-opiomelanocortin (POMC) gene in obese/diabetic Japanese. Int J Obes Relat Metab Disord. 2002;26:730–1. [PubMed: 12032760]
  • Ozen S, Aldemir O. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency. Genet Couns. 2012;23:493–5. [PubMed: 23431750]
  • Rosmond R, Ukkola O, Bouchard C, Björntorp P. Polymorphisms in exon 3 of the proopiomelanocortin gene in relation to serum leptin, salivary cortisol, and obesity in Swedish men. Metabolism. 2002;51:642–4. [PubMed: 11979399]
  • Santoro N, Perrone L, Cirillo G, Raimondo P, Amato A, Coppola F, Santarpia M, D'Aniello A, Miraglia Del Giudice E. Weight loss in obese children carrying the proopiomelanocortin R236G variant. J Endocrinol Invest. 2006;29:226–30. [PubMed: 16682835]
  • Sutton BS, Langefeld CD, Williams AH, Norris JM, Saad MF, Haffner SM, Bowden DW. Association of proopiomelanocortin gene polymorphisms with obesity in the IRAS family study. Obes Res. 2005;13:1491–8. [PubMed: 16222047]
  • Suviolahti E, Ridderstråle M, Almgren P, Klannemark M, Melander O, Carlsson E, Carlsson M, Hedenbro J, Orho-Melander M. Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals. Int J Obes Relat Metab Disord. 2003;27:1204–11. [PubMed: 14513068]

Chapter Notes

Revision History

  • 12 December 2013 (bp) Review posted live
  • 13 August 2013 (bgc) Original submission
Copyright © 1993-2018, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2018 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK174451PMID: 24354022

Views

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed
  • Gene
    Locus Links

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...