MCID: OBS081
MIFTS: 34

Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Metabolic diseases

Aliases & Classifications for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

MalaCards integrated aliases for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

Name: Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair 57
Proopiomelanocortin Deficiency 57 24 53 25 29 6 40 73
Pomc Deficiency 24 53 25 59
Obesity, Adrenal Insufficiency, and Red Hair Due to Pomc Deficiency 57 13
Obesity, Early-Onset, Adrenal Insufficiency, and Red Hair 53 25
Obesity Due to Pro-Opiomelanocortin Deficiency 53 59
Pro-Opiomelanocortinin Deficiency 75
Proopiomelanocortin 13
Obairh 57
Pomcd 75

Characteristics:

Orphanet epidemiological data:

59
obesity due to pro-opiomelanocortin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
gonadotropin, growth hormone, and tsh deficiency may become apparent in the teenage years
favorable response to treatment of hyperphagia with setmelanotide, a melanocortin-4 receptor agonist


HPO:

32
obesity, early-onset, with adrenal insufficiency and red hair:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare endocrine diseases


Summaries for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

NIH Rare Diseases : 53 Proopiomelanocortin (POMC) deficiency is characterized by severe obesity that begins at an early age. Affected infants are usually a normal weight at birth, but they are constantly hungry, which leads to excessive feeding and weight gain during the first year and throughout life. In addition, people with this condition have low levels of a hormone known as adrenocorticotropic hormone (ACTH) which leads to adrenal insufficiency. They also tend to have red hair and pale skin. POMC deficiency is caused by mutations in the POMC gene. The condition is inherited in an autosomal recessive pattern. Adrenal insufficiency requires prompt treatment with hydrocortisone to avoid life-threatening complications.  

MalaCards based summary : Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair, also known as proopiomelanocortin deficiency, is related to adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency and neuronitis. An important gene associated with Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair is POMC (Proopiomelanocortin). The drugs alpha-MSH and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include skin, pituitary and thyroid, and related phenotypes are obesity and failure to thrive

OMIM : 57 OBAIRH is an autosomal recessive endocrine disorder characterized by early-onset obesity due to severe hyperphagia, pigmentary abnormalities, mainly pale skin and red hair, and secondary hypocortisolism. In the neonatal period, affected individuals are prone to hypoglycemia, hyperbilirubinemia, and cholestasis that may result in death if not treated. The disorder results from mutation in the POMC gene, which encodes a preproprotein that is processed into a range of bioactive peptides, including alpha-melanocyte-stimulating hormone (MSH) and ACTH (summary by Kuhnen et al., 2016 and Clement et al., 2008). (609734)

UniProtKB/Swiss-Prot : 75 Pro-opiomelanocortinin deficiency: Affected individuals present early-onset obesity, adrenal insufficiency and red hair.

Genetics Home Reference : 25 Proopiomelanocortin (POMC) deficiency causes severe obesity that begins at an early age. In addition to obesity, people with this condition have low levels of a hormone known as adrenocorticotropic hormone (ACTH) and tend to have red hair and pale skin.

GeneReviews: NBK174451

Related Diseases for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Diseases related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 10.9
2 neuronitis 10.3
3 leukemia 10.1
4 conn's syndrome 10.1
5 diabetes mellitus, noninsulin-dependent 9.8
6 diabetes mellitus 9.8
7 thyroiditis 9.8

Graphical network of the top 20 diseases related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:



Diseases related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Symptoms & Phenotypes for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Symptoms via clinical synopsis from OMIM:

57
Laboratory Abnormalities:
hyperbilirubinemia
decreased plasma cortisol

Abdomen Gastrointestinal:
hyperphagia

Abdomen Liver:
cholestasis, early-onset, neonatal
hepatic failure, neonatal (in some patients)

Skin Nails Hair Skin:
pale skin (in most patients)

Endocrine Features:
adrenal hypoplasia
adrenal insufficiency
gonadotropin deficiency
delayed or absent puberty
acth deficiency
more
Growth Weight:
obesity, early-onset

Skin Nails Hair:
pigmentation abnormalities (in most patients)

Skin Nails Hair Hair:
red hair (in most patients)


Clinical features from OMIM:

609734

Human phenotypes related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

59 32 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 obesity 59 32 Obligate (100%) HP:0001513
2 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
3 delayed skeletal maturation 59 32 occasional (7.5%) Occasional (29-5%) HP:0002750
4 delayed puberty 59 32 occasional (7.5%) Occasional (29-5%) HP:0000823
5 acanthosis nigricans 59 32 occasional (7.5%) Occasional (29-5%) HP:0000956
6 hyperinsulinemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000842
7 cholestasis 59 32 frequent (33%) Frequent (79-30%) HP:0001396
8 polyphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002591
9 increased adipose tissue 59 32 obligate (100%) Obligate (100%) HP:0009126
10 pituitary hypothyroidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0008245
11 hypopigmentation of the skin 59 32 frequent (33%) Frequent (79-30%) HP:0001010
12 hypoglycemic seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0002173
13 growth hormone deficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000824
14 central adrenal insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0011734
15 gonadotropin deficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0008213
16 red hair 59 32 frequent (33%) Frequent (79-30%) HP:0002297
17 childhood-onset truncal obesity 59 32 frequent (33%) Frequent (79-30%) HP:0008915
18 growth delay 59 Occasional (29-5%)
19 adrenal insufficiency 32 HP:0000846
20 adrenocorticotropic hormone deficiency 32 HP:0011748

Drugs & Therapeutics for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Drugs for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 alpha-MSH Phase 2, Phase 3 581-05-5
2 Hormone Antagonists Phase 2, Phase 3
3 Hormones Phase 2, Phase 3
4 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Setmelanotide for the Treatment of Early-Onset POMC Deficiency Obesity Recruiting NCT02896192 Phase 2, Phase 3 Setmelanotide;Placebo
2 Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity Recruiting NCT03013543 Phase 2, Phase 3 Setmelanotide

Search NIH Clinical Center for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Genetic Tests for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Genetic tests related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

# Genetic test Affiliating Genes
1 Proopiomelanocortin Deficiency 29 POMC

Anatomical Context for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

MalaCards organs/tissues related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

41
Skin, Pituitary, Thyroid

Publications for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Articles related to Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

# Title Authors Year
1
Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice. ( 27870313 )
2017
2
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. ( 27468060 )
2016
3
Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice on a nonagouti (a/a) genetic background. ( 15564334 )
2005
4
The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin. ( 15231703 )
2004
5
Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. ( 14557433 )
2003
6
Proopiomelanocortin Deficiency ( 24354022 )
1993

Variations for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

ClinVar genetic disease variations for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair:

6
(show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 POMC NM_001035256.2(POMC): c.-11C> A single nucleotide variant Pathogenic rs753856820 GRCh38 Chromosome 2, 25164783: 25164783
2 POMC NM_001035256.2(POMC): c.-11C> A single nucleotide variant Pathogenic rs753856820 GRCh37 Chromosome 2, 25387652: 25387652
3 POMC NM_001035256.2(POMC): c.313G> T (p.Glu105Ter) single nucleotide variant Pathogenic rs121918111 GRCh37 Chromosome 2, 25384441: 25384441
4 POMC NM_001035256.2(POMC): c.313G> T (p.Glu105Ter) single nucleotide variant Pathogenic rs121918111 GRCh38 Chromosome 2, 25161572: 25161572
5 POMC NM_001035256.2(POMC): c.433delC (p.Arg145Alafs) deletion Pathogenic rs796065034 GRCh38 Chromosome 2, 25161452: 25161452
6 POMC NM_001035256.2(POMC): c.433delC (p.Arg145Alafs) deletion Pathogenic rs796065034 GRCh37 Chromosome 2, 25384321: 25384321
7 POMC NM_001035256.2(POMC): c.403_404dupGG (p.Lys136Alafs) duplication Pathogenic rs796065035 GRCh38 Chromosome 2, 25161481: 25161482
8 POMC NM_001035256.2(POMC): c.403_404dupGG (p.Lys136Alafs) duplication Pathogenic rs796065035 GRCh37 Chromosome 2, 25384350: 25384351
9 POMC NM_001035256.2(POMC): c.151A> T (p.Lys51Ter) single nucleotide variant Pathogenic rs121918112 GRCh37 Chromosome 2, 25384603: 25384603
10 POMC NM_001035256.2(POMC): c.151A> T (p.Lys51Ter) single nucleotide variant Pathogenic rs121918112 GRCh38 Chromosome 2, 25161734: 25161734
11 POMC POMC, 1-BP DEL, NT6996 deletion Pathogenic
12 POMC NM_001035256.2(POMC): c.289_297dupAGCAGCGGC (p.Gly99_Ala100insSerSerGly) duplication Likely benign rs10654394 GRCh38 Chromosome 2, 25161588: 25161596
13 POMC NM_001035256.2(POMC): c.289_297dupAGCAGCGGC (p.Gly99_Ala100insSerSerGly) duplication Likely benign rs10654394 GRCh37 Chromosome 2, 25384457: 25384465
14 POMC NM_001035256.2(POMC): c.*120A> G single nucleotide variant Uncertain significance rs886055853 GRCh37 Chromosome 2, 25383830: 25383830
15 POMC NM_001035256.2(POMC): c.*120A> G single nucleotide variant Uncertain significance rs886055853 GRCh38 Chromosome 2, 25160961: 25160961
16 POMC NM_001035256.2(POMC): c.282C> T (p.Ser94=) single nucleotide variant Likely benign rs28930368 GRCh38 Chromosome 2, 25161603: 25161603
17 POMC NM_001035256.2(POMC): c.282C> T (p.Ser94=) single nucleotide variant Likely benign rs28930368 GRCh37 Chromosome 2, 25384472: 25384472
18 POMC NM_001035256.2(POMC): c.18C> T (p.Cys6=) single nucleotide variant Uncertain significance rs8192605 GRCh38 Chromosome 2, 25164755: 25164755
19 POMC NM_001035256.2(POMC): c.18C> T (p.Cys6=) single nucleotide variant Uncertain significance rs8192605 GRCh37 Chromosome 2, 25387624: 25387624
20 POMC NM_001035256.2(POMC): c.4C> T (p.Pro2Ser) single nucleotide variant Uncertain significance rs752925315 GRCh38 Chromosome 2, 25164769: 25164769
21 POMC NM_001035256.2(POMC): c.4C> T (p.Pro2Ser) single nucleotide variant Uncertain significance rs752925315 GRCh37 Chromosome 2, 25387638: 25387638
22 POMC NM_001035256.2(POMC): c.-203A> G single nucleotide variant Uncertain significance rs139229417 GRCh38 Chromosome 2, 25168630: 25168630
23 POMC NM_001035256.2(POMC): c.-203A> G single nucleotide variant Uncertain significance rs139229417 GRCh37 Chromosome 2, 25391499: 25391499
24 POMC NM_001035256.2(POMC): c.474G> T (p.Lys158Asn) single nucleotide variant Uncertain significance rs373721473 GRCh38 Chromosome 2, 25161411: 25161411
25 POMC NM_001035256.2(POMC): c.474G> T (p.Lys158Asn) single nucleotide variant Uncertain significance rs373721473 GRCh37 Chromosome 2, 25384280: 25384280
26 POMC NM_001035256.2(POMC): c.-70-13C> T single nucleotide variant Uncertain significance rs886055855 GRCh38 Chromosome 2, 25165698: 25165698
27 POMC NM_001035256.2(POMC): c.-70-13C> T single nucleotide variant Uncertain significance rs886055855 GRCh37 Chromosome 2, 25388567: 25388567
28 POMC NM_001035256.2(POMC): c.*28delT deletion Uncertain significance rs756770132 GRCh37 Chromosome 2, 25383922: 25383922
29 POMC NM_001035256.2(POMC): c.*28delT deletion Uncertain significance rs756770132 GRCh38 Chromosome 2, 25161053: 25161053
30 POMC NM_001035256.2(POMC): c.585C> T (p.Ala195=) single nucleotide variant Likely benign rs2071345 GRCh38 Chromosome 2, 25161300: 25161300
31 POMC NM_001035256.2(POMC): c.585C> T (p.Ala195=) single nucleotide variant Likely benign rs2071345 GRCh37 Chromosome 2, 25384169: 25384169
32 POMC NM_001035256.2(POMC): c.*63C> T single nucleotide variant Likely benign rs1042571 GRCh37 Chromosome 2, 25383887: 25383887
33 POMC NM_001035256.2(POMC): c.*63C> T single nucleotide variant Likely benign rs1042571 GRCh38 Chromosome 2, 25161018: 25161018
34 POMC NM_001035256.2(POMC): c.158A> G (p.Asp53Gly) single nucleotide variant Uncertain significance rs28932470 GRCh38 Chromosome 2, 25161727: 25161727
35 POMC NM_001035256.2(POMC): c.158A> G (p.Asp53Gly) single nucleotide variant Uncertain significance rs28932470 GRCh37 Chromosome 2, 25384596: 25384596
36 POMC NM_001035256.2(POMC): c.-70-11T> C single nucleotide variant Uncertain significance rs886055854 GRCh38 Chromosome 2, 25165696: 25165696
37 POMC NM_001035256.2(POMC): c.-70-11T> C single nucleotide variant Uncertain significance rs886055854 GRCh37 Chromosome 2, 25388565: 25388565
38 POMC NM_001035256.2(POMC): c.133-2A> C single nucleotide variant Pathogenic GRCh37 Chromosome 2, 25384623: 25384623
39 POMC NM_001035256.2(POMC): c.133-2A> C single nucleotide variant Pathogenic GRCh38 Chromosome 2, 25161754: 25161754
40 POMC POMC, 1-BP INS, 6922C insertion Pathogenic

Expression for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Search GEO for disease gene expression data for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair.

Pathways for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

GO Terms for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

Sources for Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....