GCCD4
MCID: GLC105
MIFTS: 34

Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (GCCD4)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

MalaCards integrated aliases for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

Name: Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency 57 74 29 6
Gccd4 57 74
Glucocorticoid Deficiency 4, with or Without Mineralocorticoid Deficiency 57
Familial Glucocorticoid Deficiency 4 74
Glucocorticoid Deficiency 4 72
Fgd4 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable features may be present
patients may present with recurrent illnesses or infections, or shock
disease is life-threatening if untreated


HPO:

32
glucocorticoid deficiency 4 with or without mineralocorticoid deficiency:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

MeSH 44 D000309
UMLS 72 C3553587

Summaries for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

UniProtKB/Swiss-Prot : 74 Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency: 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 4 with or Without Mineralocorticoid Deficiency, also known as gccd4, is related to charcot-marie-tooth disease, type 4h and charcot-marie-tooth disease. An important gene associated with Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency is NNT (Nicotinamide Nucleotide Transhydrogenase). The drugs Paclitaxel and Antineoplastic Agents, Phytogenic have been mentioned in the context of this disorder. Affiliated tissues include cortex, adrenal cortex and breast, and related phenotypes are precocious puberty and cryptorchidism

OMIM : 57 Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by an inability of the adrenal cortex to produce cortisol in response to stimulation by adrenocorticotropic hormone (ACTH). Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, hypoglycemia, convulsions, and shock. The disease is life-threatening if untreated (summary by Meimaridou et al., 2012). For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200). (614736)

Related Diseases for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Graphical network of the top 20 diseases related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:



Diseases related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency

Symptoms & Phenotypes for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Human phenotypes related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 precocious puberty 32 occasional (7.5%) HP:0000826
2 cryptorchidism 32 occasional (7.5%) HP:0000028
3 hyponatremia 32 occasional (7.5%) HP:0002902
4 hyperkalemia 32 occasional (7.5%) HP:0002153
5 renal salt wasting 32 occasional (7.5%) HP:0000127
6 congenital hypothyroidism 32 occasional (7.5%) HP:0000851
7 hypoglycemic coma 32 occasional (7.5%) HP:0001325
8 seizures 32 HP:0001250
9 failure to thrive 32 HP:0001508
10 hypoglycemia 32 HP:0001943

Symptoms via clinical synopsis from OMIM:

57
Genitourinary External Genitalia Male:
precocious puberty

Growth Other:
failure to thrive

Genitourinary Internal Genitalia Male:
cryptorchidism
testicular enlargement
testicular adrenal rest tumors
leydig cell tumors

Skin Nails Hair Skin:
hyperpigmentation

Endocrine Features:
precocious puberty
hypothyroidism, congenital (rare)

Metabolic Features:
hypoglycemia
salt wasting
addisonian crisis

Laboratory Abnormalities:
hyponatremia
hyperkalemia
elevated acth
low cortisol level
unresponsive to acth stimulation
more
Neurologic Central Nervous System:
seizures, hypoglycemic
coma, hypoglycemic

Clinical features from OMIM:

614736

Drugs & Therapeutics for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Drugs for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paclitaxel Approved, Vet_approved Phase 3 33069-62-4 36314
2 Antineoplastic Agents, Phytogenic Phase 3
3 Halichondrin B Phase 3
4 Tubulin Modulators Phase 3
5 Albumin-Bound Paclitaxel Phase 3
6 Antimitotic Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized Phase III Trial of Eribulin Compared to Standard Weekly Paclitaxel as First- or Second-Line Therapy for Locally Recurrent or Metastatic Breast Cancer Suspended NCT02037529 Phase 3 Eribulin Mesylate;Paclitaxel

Search NIH Clinical Center for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency

Genetic Tests for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Genetic tests related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

# Genetic test Affiliating Genes
1 Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency 29 NNT

Anatomical Context for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

MalaCards organs/tissues related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

41
Cortex, Adrenal Cortex, Breast, Prostate, Brain, Testes, Retina

Publications for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Articles related to Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

(show all 41)
# Title Authors PMID Year
1
NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects. 8 71
27129361 2016
2
A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency. 8 71
23474776 2013
3
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. 8 71
22634753 2012
4
Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency. 8
25879317 2015
5
Combined mineralocorticoid and glucocorticoid deficiency is caused by a novel founder nicotinamide nucleotide transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress. 8
26070314 2015
6
A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4. 38
31152969 2019
7
Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer. 38
30558664 2018
8
Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review. 38
30044129 2018
9
Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. 38
28902413 2017
10
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. 38
28847448 2017
11
A novel mutation in the FGD4 gene causing Charcot-Marie-Tooth disease. 38
28543957 2017
12
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. 38
28321468 2017
13
Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes. 38
28130497 2017
14
The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. 38
27650539 2016
15
Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise. 38
27832807 2016
16
Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients. 38
27736846 2016
17
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance). 38
26763541 2016
18
[Peroneal myoatrophy type 4H FGD4 new gene mutation in one case and literature review]. 38
26957070 2016
19
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. 38
26400421 2015
20
Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects. 38
26086592 2015
21
Aluminum Nanoparticles Induce ERK and p38MAPK Activation in Rat Brain. 38
24386518 2013
22
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation. 38
23770104 2013
23
Charcot-Marie-Tooth Neuropathy Type 4H 38
23926620 2013
24
A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family. 38
23550889 2013
25
Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes. 38
23781959 2013
26
Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan. 38
23466821 2013
27
p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells. 38
23380069 2013
28
Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells. 38
23171661 2012
29
A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. 38
22843789 2012
30
Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H). 38
22734899 2012
31
Peripheral blood DNA methylation profiles are indicative of head and neck squamous cell carcinoma: an epigenome-wide association study. 38
22430805 2012
32
Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells. 38
22589722 2012
33
Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking. 38
22295116 2012
34
Genetic spectrum of hereditary neuropathies with onset in the first year of life. 38
21840889 2011
35
Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. 38
19332693 2009
36
A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. 38
19221294 2009
37
[Ultrastructural lesions of axonal mitochondria in patients with childhood-onset Charcot-Marie-Tooth disease due to MFN2 mutations]. 38
19718987 2009
38
Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations. 38
18957892 2008
39
Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. 38
17564959 2007
40
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. 38
17564972 2007
41
Charcot-Marie-Tooth Neuropathy Type 4 38
20301641 1998

Variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

ClinVar genetic disease variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NNT NM_012343.4(NNT): c.1598C> T (p.Ala533Val) single nucleotide variant Pathogenic rs387907232 5:43649402-43649402 5:43649300-43649300
2 NNT NM_012343.4(NNT): c.600-1del deletion Pathogenic rs786205344 5:43619133-43619133 5:43619031-43619031
3 NNT NM_012343.4(NNT): c.2930T> C (p.Leu977Pro) single nucleotide variant Pathogenic rs387907233 5:43700274-43700274 5:43700172-43700172
4 NNT NM_012343.4(NNT): c.1107_1110del (p.Thr369_His370insTer) deletion Pathogenic rs786205345 5:43644721-43644724 5:43644619-43644622
5 NNT NM_012343.4(NNT): c.3027T> G (p.Asn1009Lys) single nucleotide variant Pathogenic rs370273690 5:43702754-43702754 5:43702652-43702652
6 NNT NM_012343.4(NNT): c.3022G> C (p.Ala1008Pro) single nucleotide variant Pathogenic rs387907234 5:43702749-43702749 5:43702647-43702647
7 NNT NM_012343.4(NNT): c.1259dup (p.His421fs) duplication Pathogenic rs864309519 5:43644873-43644873 5:43644771-43644771
8 NNT NM_012343.4(NNT): c.644T> C (p.Phe215Ser) single nucleotide variant Pathogenic rs886039786 5:43619178-43619178 5:43619076-43619076
9 NNT NM_012343.4(NNT): c.385C> T (p.Arg129Ter) single nucleotide variant Pathogenic rs886039789 5:43615953-43615953 5:43615851-43615851
10 NNT NM_012343.4(NNT): c.211C> T (p.Arg71Ter) single nucleotide variant Pathogenic rs886039790 5:43613069-43613069 5:43612967-43612967

UniProtKB/Swiss-Prot genetic disease variations for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency:

74 (show all 11)
# Symbol AA change Variation ID SNP ID
1 NNT p.Ser193Asn VAR_068781 rs867004061
2 NNT p.Thr357Ala VAR_068782 rs144740886
3 NNT p.His365Pro VAR_068783
4 NNT p.Pro437Leu VAR_068784 rs781183677
5 NNT p.Ala533Val VAR_068785 rs387907232
6 NNT p.Gly664Arg VAR_068786 rs371979800
7 NNT p.Gly678Arg VAR_068787
8 NNT p.Gly862Asp VAR_068788 rs147442141
9 NNT p.Leu977Pro VAR_068789 rs387907233
10 NNT p.Ala1008Pro VAR_068790 rs387907234
11 NNT p.Asn1009Lys VAR_068791 rs370273690

Expression for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Search GEO for disease gene expression data for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid Deficiency.

Pathways for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

GO Terms for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

Sources for Glucocorticoid Deficiency 4 with or Without Mineralocorticoid...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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30 HGMD
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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