MCID: GLC042
MIFTS: 39

Glucocorticoid Deficiency 1

Categories: Genetic diseases, Endocrine diseases

Aliases & Classifications for Glucocorticoid Deficiency 1

MalaCards integrated aliases for Glucocorticoid Deficiency 1:

Name: Glucocorticoid Deficiency 1 57 75 73
Acth Resistance 57 76 75 29 55 6 40
Glucocorticoid Deficiency, Due to Acth Unresponsiveness 57 13
Familial Glucocorticoid Deficiency 1 57 75
Adrenal Unresponsiveness to Acth 57 75
Gccd1 57 75
Fgd1 57 75
Hereditary Unresponsiveness to Adrenocorticotropic Hormone 75
Familial Glucocorticoid Deficiency 1; Fgd1 57
Isolated Glucocorticoid Deficiency 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
glucocorticoid deficiency 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Glucocorticoid Deficiency 1

UniProtKB/Swiss-Prot : 75 Glucocorticoid deficiency 1: A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.

MalaCards based summary : Glucocorticoid Deficiency 1, also known as acth resistance, is related to achalasia-addisonianism-alacrima syndrome and familial glucocorticoid deficiency. An important gene associated with Glucocorticoid Deficiency 1 is MC2R (Melanocortin 2 Receptor), and among its related pathways/superpathways are Aldosterone synthesis and secretion and G alpha (s) signalling events. Affiliated tissues include pituitary, adrenal gland and cortex, and related phenotypes are seizures and failure to thrive

OMIM : 57 Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol and, because of the failure of the negative feedback loop to the pituitary and hypothalamus, grossly elevated ACTH levels (summary by Clark et al., 2009). (202200)

Wikipedia : 76 Glucocorticoid deficiency 1 (FGD or GCCD) is an adrenocortical failure characterized by low levels of... more...

Related Diseases for Glucocorticoid Deficiency 1

Graphical network of the top 20 diseases related to Glucocorticoid Deficiency 1:



Diseases related to Glucocorticoid Deficiency 1

Symptoms & Phenotypes for Glucocorticoid Deficiency 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
coma

Laboratory Abnormalities:
hypoglycemia
low to undetectable plasma cortisol
elevated plasma acth
normal plasma renin
normal plasma aldosterone

Skeletal:
advanced bone age

Metabolic Features:
recurrent hypoglycemic episodes

Growth Other:
failure to thrive

Growth Height:
tall stature

Skin Nails Hair Skin:
hyperpigmentation

Immunology:
frequent, severe infections


Clinical features from OMIM:

202200

Human phenotypes related to Glucocorticoid Deficiency 1:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 failure to thrive 32 HP:0001508
3 coma 32 HP:0001259
4 recurrent infections 32 HP:0002719
5 tall stature 32 HP:0000098
6 accelerated skeletal maturation 32 HP:0005616
7 increased circulating acth level 32 HP:0003154
8 decreased circulating cortisol level 32 HP:0008163
9 recurrent hypoglycemia 32 HP:0001988
10 hyperpigmentation of the skin 32 HP:0000953

Drugs & Therapeutics for Glucocorticoid Deficiency 1

Search Clinical Trials , NIH Clinical Center for Glucocorticoid Deficiency 1

Genetic Tests for Glucocorticoid Deficiency 1

Genetic tests related to Glucocorticoid Deficiency 1:

# Genetic test Affiliating Genes
1 Acth Resistance 29 MC2R

Anatomical Context for Glucocorticoid Deficiency 1

MalaCards organs/tissues related to Glucocorticoid Deficiency 1:

41
Pituitary, Adrenal Gland, Cortex, Hypothalamus, Adrenal Cortex, Skin, Bone

Publications for Glucocorticoid Deficiency 1

Articles related to Glucocorticoid Deficiency 1:

# Title Authors Year
1
Ketogenic diet therapy can improve ACTH-resistant West syndrome in Japan. ( 24559837 )
2014
2
Heterogeneity in the molecular basis of ACTH resistance syndrome. ( 18426811 )
2008
3
Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes. ( 17466001 )
2007
4
The genetics of ACTH resistance syndromes. ( 17161331 )
2006
5
The activation function of steroidogenic factor-1 is impaired in ACTH-resistant Y1 mutants. ( 11196409 )
2000
6
[ACTH resistance syndromes]. ( 11084394 )
2000
7
ACTH resistance syndromes. ( 10698592 )
1999
8
Genetic heterogeneity of adrenocorticotropin (ACTH) resistance syndromes: identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency. ( 9758716 )
1998
9
Exclusion of the adrenocorticotropin (ACTH) receptor (MC2R) locus in some families with ACTH resistance but no mutations of the MC2R coding sequence (familial glucocorticoid deficiency type 2). ( 9768670 )
1998
10
Molecular insights into inherited ACTH resistance syndromes. ( 18407210 )
1994

Variations for Glucocorticoid Deficiency 1

UniProtKB/Swiss-Prot genetic disease variations for Glucocorticoid Deficiency 1:

75
# Symbol AA change Variation ID SNP ID
1 MC2R p.Ser74Ile VAR_003510 rs104894658
2 MC2R p.Ser120Arg VAR_003511 rs104894656
3 MC2R p.Arg128Cys VAR_003512 rs104894657
4 MC2R p.Arg146His VAR_003513 rs758709668
5 MC2R p.Asp103Asn VAR_010702 rs768093045
6 MC2R p.Arg137Trp VAR_010703 rs104894660
7 MC2R p.Asp107Asn VAR_015095 rs104894661
8 MC2R p.Cys251Phe VAR_015096 rs104894662
9 MC2R p.Tyr254Cys VAR_015295 rs28940892

ClinVar genetic disease variations for Glucocorticoid Deficiency 1:

6
(show all 32)
# Gene Variation Type Significance SNP ID Assembly Location
1 MRAP NM_206898.1(MRAP): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs80358231 GRCh37 Chromosome 21, 33671285: 33671285
2 MRAP NM_206898.1(MRAP): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs80358231 GRCh38 Chromosome 21, 32298974: 32298974
3 MC2R NM_000529.2(MC2R): c.221G> T (p.Ser74Ile) single nucleotide variant Pathogenic rs104894658 GRCh37 Chromosome 18, 13885297: 13885297
4 MC2R NM_000529.2(MC2R): c.221G> T (p.Ser74Ile) single nucleotide variant Pathogenic rs104894658 GRCh38 Chromosome 18, 13885298: 13885298
5 MC2R NM_000529.2(MC2R): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs104894659 GRCh37 Chromosome 18, 13884917: 13884917
6 MC2R NM_000529.2(MC2R): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs104894659 GRCh38 Chromosome 18, 13884918: 13884918
7 MC2R NM_000529.2(MC2R): c.360C> G (p.Ser120Arg) single nucleotide variant Pathogenic rs104894656 GRCh37 Chromosome 18, 13885158: 13885158
8 MC2R NM_000529.2(MC2R): c.360C> G (p.Ser120Arg) single nucleotide variant Pathogenic rs104894656 GRCh38 Chromosome 18, 13885159: 13885159
9 MC2R NM_000529.2(MC2R): c.382C> T (p.Arg128Cys) single nucleotide variant Pathogenic rs104894657 GRCh37 Chromosome 18, 13885136: 13885136
10 MC2R NM_000529.2(MC2R): c.382C> T (p.Arg128Cys) single nucleotide variant Pathogenic rs104894657 GRCh38 Chromosome 18, 13885137: 13885137
11 MC2R NM_000529.2(MC2R): c.319G> A (p.Asp107Asn) single nucleotide variant Pathogenic rs104894661 GRCh37 Chromosome 18, 13885199: 13885199
12 MC2R NM_000529.2(MC2R): c.319G> A (p.Asp107Asn) single nucleotide variant Pathogenic rs104894661 GRCh38 Chromosome 18, 13885200: 13885200
13 MC2R MC2R, 1-BP INS, 1347A insertion Pathogenic
14 MC2R NM_000529.2(MC2R): c.752G> T (p.Cys251Phe) single nucleotide variant Pathogenic rs104894662 GRCh37 Chromosome 18, 13884766: 13884766
15 MC2R NM_000529.2(MC2R): c.752G> T (p.Cys251Phe) single nucleotide variant Pathogenic rs104894662 GRCh38 Chromosome 18, 13884767: 13884767
16 MC2R NM_000529.2(MC2R): c.409C> T (p.Arg137Trp) single nucleotide variant Pathogenic rs104894660 GRCh37 Chromosome 18, 13885109: 13885109
17 MC2R NM_000529.2(MC2R): c.409C> T (p.Arg137Trp) single nucleotide variant Pathogenic rs104894660 GRCh38 Chromosome 18, 13885110: 13885110
18 MC2R NM_000529.2(MC2R): c.761A> G (p.Tyr254Cys) single nucleotide variant Pathogenic rs28940892 GRCh37 Chromosome 18, 13884757: 13884757
19 MC2R NM_000529.2(MC2R): c.761A> G (p.Tyr254Cys) single nucleotide variant Pathogenic rs28940892 GRCh38 Chromosome 18, 13884758: 13884758
20 MC2R NM_000529.2(MC2R): c.376G> T (p.Ala126Ser) single nucleotide variant Pathogenic rs267607231 GRCh37 Chromosome 18, 13885142: 13885142
21 MC2R NM_000529.2(MC2R): c.376G> T (p.Ala126Ser) single nucleotide variant Pathogenic rs267607231 GRCh38 Chromosome 18, 13885143: 13885143
22 MC2R NM_000529.2(MC2R): c.674T> G (p.Leu225Arg) single nucleotide variant Pathogenic GRCh37 Chromosome 18, 13884844: 13884844
23 MC2R NM_000529.2(MC2R): c.674T> G (p.Leu225Arg) single nucleotide variant Pathogenic GRCh38 Chromosome 18, 13884845: 13884845
24 MC2R NM_000529.2(MC2R): c.459dup (p.Ile154Hisfs) duplication Pathogenic GRCh38 Chromosome 18, 13885060: 13885060
25 MC2R NM_000529.2(MC2R): c.459dup (p.Ile154Hisfs) duplication Pathogenic GRCh37 Chromosome 18, 13885059: 13885059
26 MC2R NM_000529.2(MC2R): c.424G> T (p.Val142Leu) single nucleotide variant Pathogenic rs199950178 GRCh37 Chromosome 18, 13885094: 13885094
27 MC2R NM_000529.2(MC2R): c.424G> T (p.Val142Leu) single nucleotide variant Pathogenic rs199950178 GRCh38 Chromosome 18, 13885095: 13885095
28 MRAP NM_206898.1(MRAP): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic GRCh38 Chromosome 21, 32298972: 32298972
29 MRAP NM_206898.1(MRAP): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic GRCh37 Chromosome 21, 33671283: 33671283
30 MRAP NM_206898.1(MRAP): c.106+1delG deletion Pathogenic GRCh38 Chromosome 21, 32299078: 32299078
31 MC2R NM_000529.2(MC2R): c.702delC (p.Phe235Leufs) deletion Pathogenic GRCh37 Chromosome 18, 13884816: 13884816
32 MC2R NM_000529.2(MC2R): c.702delC (p.Phe235Leufs) deletion Pathogenic GRCh38 Chromosome 18, 13884817: 13884817

Expression for Glucocorticoid Deficiency 1

Search GEO for disease gene expression data for Glucocorticoid Deficiency 1.

GO Terms for Glucocorticoid Deficiency 1

Biological processes related to Glucocorticoid Deficiency 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuropeptide signaling pathway GO:0007218 8.62 MC2R POMC

Molecular functions related to Glucocorticoid Deficiency 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 type 4 melanocortin receptor binding GO:0031782 9.16 MRAP POMC
2 type 3 melanocortin receptor binding GO:0031781 8.96 MRAP POMC
3 type 1 melanocortin receptor binding GO:0070996 8.62 MRAP POMC

Sources for Glucocorticoid Deficiency 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
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35 ICD9CM
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37 KEGG
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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