OBAIRH
MCID: OBS081
MIFTS: 37

Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair (OBAIRH)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases, Skin 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 72
Proopiomelanocortin Deficiency 57 20 43 29 6 70
Pomc Deficiency 20 43 58
Obesity, Adrenal Insufficiency, and Red Hair Due to Pomc Deficiency 57 13
Obesity, Early-Onset, Adrenal Insufficiency, and Red Hair 20 43
Obesity Due to Pro-Opiomelanocortin Deficiency 20 58
Obairh 57 72
Pro-Opiomelanocortinin Deficiency 72

Characteristics:

Orphanet epidemiological data:

58
obesity due to pro-opiomelanocortin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
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:

31
obesity, early-onset, with adrenal insufficiency and red hair:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare endocrine diseases


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

MedlinePlus Genetics : 43 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.Affected infants are usually a normal weight at birth, but they are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely obese by age 1. Affected individuals experience excessive hunger and remain obese for life. It is unclear if these individuals are prone to weight-related conditions like cardiovascular disease or type 2 diabetes.Low levels of ACTH lead to a condition called adrenal insufficiency, which occurs when the pair of small glands on top of the kidneys (the adrenal glands) do not produce enough hormones. Adrenal insufficiency often results in periods of severely low blood sugar (hypoglycemia) in people with POMC deficiency, which can cause seizures, elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia), and a reduced ability to produce and release a digestive fluid called bile (cholestasis). Without early treatment, adrenal insufficiency can be fatal.Pale skin that easily burns when exposed to the sun and red hair are common in POMC deficiency, although not everyone with the condition has these characteristics.

MalaCards based summary : Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair, also known as proopiomelanocortin deficiency, is related to body mass index quantitative trait locus 9 and body mass index quantitative trait locus 8. An important gene associated with Obesity, Early-Onset, with Adrenal Insufficiency and Red Hair is POMC (Proopiomelanocortin). The drugs Adrenocorticotropic Hormone and Melanocyte-Stimulating Hormones have been mentioned in the context of this disorder. Affiliated tissues include pituitary and thyroid, and related phenotypes are increased adipose tissue and polyphagia

GARD : 20 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.

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) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Obesity, early-onset, with adrenal insufficiency and red hair: An autosomal recessive disorder characterized by early-onset obesity due to severe hyperphagia, pigmentary abnormalities, mainly pale skin and red hair, and secondary hypocortisolism.

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

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

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

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 increased adipose tissue 58 31 obligate (100%) Obligate (100%) HP:0009126
2 polyphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002591
3 cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001396
4 hypopigmentation of the skin 58 31 frequent (33%) Frequent (79-30%) HP:0001010
5 red hair 58 31 frequent (33%) Frequent (79-30%) HP:0002297
6 central adrenal insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0011734
7 childhood-onset truncal obesity 58 31 frequent (33%) Frequent (79-30%) HP:0008915
8 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
9 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
10 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
11 hyperinsulinemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000842
12 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
13 pituitary hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0008245
14 gonadotropin deficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0008213
15 hypoglycemic seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002173
16 decreased response to growth hormone stimuation test 31 very rare (1%) HP:0000824
17 obesity 58 31 Obligate (100%) HP:0001513
18 growth delay 58 Occasional (29-5%)
19 hyperbilirubinemia 31 HP:0002904
20 adrenal hypoplasia 31 HP:0000835
21 adrenal insufficiency 31 HP:0000846
22 growth hormone deficiency 58 Occasional (29-5%)
23 adrenocorticotropic hormone deficiency 31 HP:0011748

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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 (Updated 05-Apr-2021)

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 Adrenocorticotropic Hormone Phase 2
2 Melanocyte-Stimulating Hormones Phase 2
3 beta-Endorphin Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Open Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of RM-493, a MC4R Agonist, in Early Onset POMC Deficiency Obesity Due to Bi-Allelic Loss-of-Function POMC or PCSK1 Genetic Mutation Completed NCT02896192 Phase 2, Phase 3 Setmelanotide;Placebo
2 Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity Recruiting NCT03013543 Phase 2, Phase 3 Setmelanotide
3 RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients Unknown status NCT02507492 Phase 2 RM-493
4 An Observational,Prospective Natural History Study of Early-Onset Extreme Obesity Due to Bi-Allelic Loss-of-Function Mutations in the POMC, PCSK1 or LEPR Genes Recruiting NCT03621007

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:

40
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:

(show all 13)
# Title Authors PMID Year
1
Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. 57 61 6
14557433 2003
2
Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene. 57 6
18765507 2008
3
Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. 6 57
9620771 1998
4
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. 61 57
27468060 2016
5
Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. 57
10470087 1999
6
Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases. 61
33666293 2021
7
A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index. 61
29858905 2018
8
A Patient with Proopiomelanocortin Deficiency: An Increasingly Important Diagnosis to Make. 61
28739551 2018
9
Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice. 61
27870313 2017
10
Proopiomelanocortin Deficiency – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
24354022 2013
11
Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin. 61
22077870 2011
12
The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature. 61
19221669 2009
13
The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin. 61
15231703 2004

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 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POMC NM_000939.4(POMC):c.313G>T (p.Glu105Ter) SNV Pathogenic 13353 rs121918111 GRCh37: 2:25384441-25384441
GRCh38: 2:25161572-25161572
2 POMC NM_000939.4(POMC):c.433del (p.Arg145fs) Deletion Pathogenic 13354 rs796065034 GRCh37: 2:25384321-25384321
GRCh38: 2:25161452-25161452
3 POMC NM_000939.4(POMC):c.-11C>A SNV Pathogenic 13355 rs753856820 GRCh37: 2:25387652-25387652
GRCh38: 2:25164783-25164783
4 POMC NM_000939.4(POMC):c.403_404dup (p.Lys136fs) Duplication Pathogenic 13357 rs796065035 GRCh37: 2:25384349-25384350
GRCh38: 2:25161480-25161481
5 POMC NM_000939.4(POMC):c.151A>T (p.Lys51Ter) SNV Pathogenic 13358 rs121918112 GRCh37: 2:25384603-25384603
GRCh38: 2:25161734-25161734
6 POMC POMC, 1-BP DEL, NT6996 Deletion Pathogenic 13359 GRCh37:
GRCh38:
7 POMC NM_000939.4(POMC):c.133-2A>C SNV Pathogenic 436364 rs1553400259 GRCh37: 2:25384623-25384623
GRCh38: 2:25161754-25161754
8 POMC POMC, 1-BP INS, 6922C Insertion Pathogenic 492966 GRCh37:
GRCh38:
9 POMC NM_000939.4(POMC):c.416dup (p.Tyr139Ter) Duplication Pathogenic 666581 rs1573250294 GRCh37: 2:25384337-25384338
GRCh38: 2:25161468-25161469
10 POMC NM_000939.4(POMC):c.84C>A (p.Cys28Ter) SNV Pathogenic 666582 rs1573254045 GRCh37: 2:25387558-25387558
GRCh38: 2:25164689-25164689
11 POMC NM_000939.4(POMC):c.573del (p.Asp192fs) Deletion Pathogenic 1034389 GRCh37: 2:25384181-25384181
GRCh38: 2:25161312-25161312
12 POMC NM_000939.4(POMC):c.642G>A (p.Glu214=) SNV Uncertain significance 898577 GRCh37: 2:25384112-25384112
GRCh38: 2:25161243-25161243
13 POMC NM_000939.4(POMC):c.638C>T (p.Ala213Val) SNV Uncertain significance 895579 GRCh37: 2:25384116-25384116
GRCh38: 2:25161247-25161247
14 POMC NM_000939.4(POMC):c.498C>T (p.Asp166=) SNV Uncertain significance 895580 GRCh37: 2:25384256-25384256
GRCh38: 2:25161387-25161387
15 POMC NM_000939.4(POMC):c.491C>T (p.Ala164Val) SNV Uncertain significance 895581 GRCh37: 2:25384263-25384263
GRCh38: 2:25161394-25161394
16 POMC , LOC108167315 NM_001035256.2(POMC):c.-263C>A SNV Uncertain significance 895643 GRCh37: 2:25391559-25391559
GRCh38: 2:25168690-25168690
17 POMC NM_000939.4(POMC):c.429C>G (p.His143Gln) SNV Uncertain significance 451178 rs201519174 GRCh37: 2:25384325-25384325
GRCh38: 2:25161456-25161456
18 POMC NM_000939.4(POMC):c.394C>G (p.Pro132Ala) SNV Uncertain significance 896986 GRCh37: 2:25384360-25384360
GRCh38: 2:25161491-25161491
19 POMC NM_000939.4(POMC):c.283A>G (p.Ser95Gly) SNV Uncertain significance 896987 GRCh37: 2:25384471-25384471
GRCh38: 2:25161602-25161602
20 POMC NM_000939.4(POMC):c.474G>T (p.Lys158Asn) SNV Uncertain significance 335355 rs373721473 GRCh37: 2:25384280-25384280
GRCh38: 2:25161411-25161411
21 POMC NM_000939.4(POMC):c.116C>T (p.Thr39Met) SNV Uncertain significance 897472 GRCh37: 2:25387526-25387526
GRCh38: 2:25164657-25164657
22 POMC NM_000939.4(POMC):c.801G>A (p.Glu267=) SNV Uncertain significance 898575 GRCh37: 2:25383953-25383953
GRCh38: 2:25161084-25161084
23 POMC NM_000939.4(POMC):c.583G>A (p.Ala195Thr) SNV Uncertain significance 716681 rs141309351 GRCh37: 2:25384171-25384171
GRCh38: 2:25161302-25161302
24 POMC NM_000939.4(POMC):c.*28del Deletion Uncertain significance 335353 rs756770132 GRCh37: 2:25383922-25383922
GRCh38: 2:25161053-25161053
25 POMC NM_000939.4(POMC):c.-20-906C>T SNV Uncertain significance 335361 rs886055855 GRCh37: 2:25388567-25388567
GRCh38: 2:25165698-25165698
26 POMC NM_000939.4(POMC):c.*120A>G SNV Uncertain significance 335351 rs886055853 GRCh37: 2:25383830-25383830
GRCh38: 2:25160961-25160961
27 POMC NM_000939.4(POMC):c.4C>T (p.Pro2Ser) SNV Uncertain significance 335359 rs752925315 GRCh37: 2:25387638-25387638
GRCh38: 2:25164769-25164769
28 POMC NM_000939.4(POMC):c.-20-904T>C SNV Uncertain significance 335360 rs886055854 GRCh37: 2:25388565-25388565
GRCh38: 2:25165696-25165696
29 POMC NM_000939.4(POMC):c.280_288AGCAGCGGC[3] (p.94_96SSG[3]) Microsatellite Likely benign 211935 rs10654394 GRCh37: 2:25384456-25384457
GRCh38: 2:25161587-25161588
30 POMC NM_000939.4(POMC):c.662A>G (p.Tyr221Cys) SNV Likely benign 898576 GRCh37: 2:25384092-25384092
GRCh38: 2:25161223-25161223
31 POMC NM_000939.4(POMC):c.158A>G (p.Asp53Gly) SNV Likely benign 335357 rs28932470 GRCh37: 2:25384596-25384596
GRCh38: 2:25161727-25161727
32 POMC NM_000939.4(POMC):c.18C>T (p.Cys6=) SNV Likely benign 335358 rs8192605 GRCh37: 2:25387624-25387624
GRCh38: 2:25164755-25164755
33 POMC NM_000939.4(POMC):c.261C>A (p.Phe87Leu) SNV Likely benign 710881 rs199636726 GRCh37: 2:25384493-25384493
GRCh38: 2:25161624-25161624
34 POMC NM_000939.4(POMC):c.585C>T (p.Ala195=) SNV Benign 335354 rs2071345 GRCh37: 2:25384169-25384169
GRCh38: 2:25161300-25161300
35 POMC NM_000939.4(POMC):c.706C>G (p.Arg236Gly) SNV Benign 13356 rs28932472 GRCh37: 2:25384048-25384048
GRCh38: 2:25161179-25161179
36 POMC NM_000939.4(POMC):c.*63C>T SNV Benign 335352 rs1042571 GRCh37: 2:25383887-25383887
GRCh38: 2:25161018-25161018
37 POMC NM_000939.4(POMC):c.282C>T (p.Ser94=) SNV Benign 335356 rs28930368 GRCh37: 2:25384472-25384472
GRCh38: 2:25161603-25161603
38 POMC , LOC108167315 NM_001035256.2(POMC):c.-203A>G SNV Benign 335362 rs139229417 GRCh37: 2:25391499-25391499
GRCh38: 2:25168630-25168630

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 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....