MCID: FMR011
MIFTS: 60

Fumarate Hydratase Deficiency malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases categories
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Summaries for Fumarate Hydratase Deficiency

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Genetics Home Reference:21 Fumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood.

MalaCards based summary: Fumarate Hydratase Deficiency, also known as fumarase deficiency, is related to kidney cancer and leiomyomatosis, and has symptoms including An important gene associated with Fumarate Hydratase Deficiency is FH (fumarate hydratase), and among its related pathways are Trk receptor signaling mediated by the MAPK pathway and PDGFR-alpha signaling pathway. The compounds pilocarpine and cocl2 have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and spleen, and related mouse phenotypes are renal/urinary system and limbs/digits/tail.

NIH Rare Diseases:42 Fumarase deficiency is an inherited condition that primarily affects the nervous system, especially the brain. affected infants may have microcephaly, abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), failure to thrive, seizures, and/or distinctive facial features. other signs and symptoms may include hepatosplenomegaly, an excess of red blood cells (polycythemia), and/or or deficiency of white blood cells (leukopenia). affected individuals usually survive only a few months, but a few have lived into early adulthood. this condition is caused by mutations in the fh gene and is inherited in an autosomal recessive manner. no effective treatment is currently available. last updated: 11/6/2012

Wikipedia:65 Fumarase deficiency (or fumaric aciduria), also known as \"Polygamist Down\'s\", is an autosomal... more...

Description from OMIM:46 606812

GeneReviews summary for fum

Aliases & Classifications for Fumarate Hydratase Deficiency

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Sources:
19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 44Novoseek, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Fumarate Hydratase Deficiency, Aliases & Descriptions:

Name: Fumarate Hydratase Deficiency 19 42 20 21 62
Fumarase Deficiency 19 42 22 21 46 44 48 62
 
Fumaric Aciduria 19 42 21 48 62


Classifications:



Characteristics (Orphanet epidemiological data):

48
fumarase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy; Age of death: Before age 5


External Ids:

OMIM46 606812
MESH via Orphanet35 C538191
ICD10 via Orphanet26 E88.8
UMLS via Orphanet63 C0342770, C2936826

Related Diseases for Fumarate Hydratase Deficiency

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Diseases related to Fumarate Hydratase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 43)
idRelated DiseaseScoreTop Affiliating Genes
1kidney cancer31.0VHL, FH
2leiomyomatosis31.0VHL, FH
3hypoxia10.6
4cystadenoma10.3VHL
5renal cell carcinoma10.3
6leiomyoma10.3
7uterine fibroid10.3
8hereditary leiomyomatosis and renal cell cancer10.2FH, HIF1A
9familial colorectal cancer10.2VHL, FH
10cystic kidney10.2VHL, FH
11biliary atresia10.2
12polyhydramnios10.2
13cerebritis10.2
14mitochondrial encephalomyopathy10.2
15encephalomyopathy10.2
16hypotonia10.2
17oxyphilic adenoma10.1VHL, FH
18hemangioblastoma10.1HIF1A, VHL
19erythrocytosis10.1HIF1A, VHL
20von hippel-lindau disease10.1HIF1A, VHL
21polycythemia10.1HIF1A, VHL
22diabetic retinopathy10.1HIF1A, SRF
23glioblastoma multiforme10.0VHL, HIF1A
24paraganglioma10.0VHL, FH, HIF1A
25renal clear cell carcinoma10.0HIF1A, FH, VHL
26kidney rhabdoid cancer10.0VHL, FH, HIF1A
27t-cell leukemia9.8FOS, SRF, JUNB
28stomach cancer9.8VHL, JUNB, HIF1A
29retinoblastoma9.8JUNB, FOS, VHL
30astrocytoma9.7HIF1A, FOS, VHL
31glioblastoma9.7HIF1A, FOS, VHL
32adenocarcinoma9.7HIF1A, JUNB, SRF, VHL
33rheumatoid arthritis9.7FOS, SRF, JUNB
34ovarian cancer9.7FOS, SRF, HIF1A
35osteosarcoma9.6HIF1A, JUNB, SRF, FOS
36liver cancer9.6HIF1A, JUNB, SRF, FOS
37colonic benign neoplasm9.6HIF1A, SRF, FOS
38lung cancer9.6VHL, SRF, HIF1A
39malignant glioma9.6VHL, FOS, JUNB, HIF1A
40burkitt's lymphoma9.6JUNB, SRF, FOS, VHL
41tongue squamous cell carcinoma9.5HIF1A, SRF, FOS, VHL
42pheochromocytoma9.4HIF1A, JUNB, FOS, FH, VHL
43breast cancer9.4VHL, FOS, SRF, JUNB, HIF1A

Graphical network of the top 20 diseases related to Fumarate Hydratase Deficiency:



Diseases related to fumarate hydratase deficiency

Symptoms for Fumarate Hydratase Deficiency

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Symptoms by clinical synopsis from OMIM:

606812

Clinical features from OMIM:

606812

HPO human phenotypes related to Fumarate Hydratase Deficiency:

(show all 31)
id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 high palate HP:0000218
3 microcephaly HP:0000252
4 hypertelorism HP:0000316
5 anteverted nares HP:0000463
6 visual impairment HP:0000505
7 optic atrophy HP:0000648
8 pallor HP:0000980
9 decreased subcutaneous fat HP:0001002
10 muscular hypotonia HP:0001252
11 global developmental delay HP:0001263
12 agenesis of corpus callosum HP:0001274
13 cholestasis HP:0001396
14 hepatic failure HP:0001399
15 failure to thrive HP:0001508
16 polycythemia HP:0001901
17 metabolic acidosis HP:0001942
18 frontal bossing HP:0002007
19 cerebral atrophy HP:0002059
20 polymicrogyria HP:0002126
21 status epilepticus HP:0002133
22 neurological speech impairment HP:0002167
23 intellectual disability, profound HP:0002187
24 choroid plexus cyst HP:0002190
25 hypoplasia of the brainstem HP:0002365
26 lactic acidosis HP:0003128
27 aminoaciduria HP:0003355
28 relative macrocephaly HP:0004482
29 depressed nasal bridge HP:0005280
30 cutaneous leiomyoma HP:0007620
31 open operculum HP:0100954

Drugs & Therapeutics for Fumarate Hydratase Deficiency

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Drug clinical trials:

Search ClinicalTrials for Fumarate Hydratase Deficiency

Search NIH Clinical Center for Fumarate Hydratase Deficiency

Genetic Tests for Fumarate Hydratase Deficiency

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Genetic tests related to Fumarate Hydratase Deficiency:

id Genetic test Affiliating Genes
1 Fumarate Hydratase Deficiency20 FH
2 Fumarase Deficiency22

Anatomical Context for Fumarate Hydratase Deficiency

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MalaCards organs/tissues related to Fumarate Hydratase Deficiency:

32
Brain, Eye, Spleen, Liver, Kidney

Animal Models for Fumarate Hydratase Deficiency or affiliated genes

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MGI Mouse Phenotypes related to Fumarate Hydratase Deficiency:

36 (show all 13)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.3HIF1A, JUNB, FH, VHL
2MP:00053718.3VHL, FOS, JUNB, HIF1A
3MP:00053808.3VHL, FOS, SRF, HIF1A
4MP:00020068.2HIF1A, JUNB, FOS, VHL
5MP:00107718.1HIF1A, JUNB, FOS, VHL
6MP:00028738.1HIF1A, SRF, FOS, VHL
7MP:00053858.1VHL, SRF, JUNB, HIF1A
8MP:00053907.8HIF1A, JUNB, SRF, FOS, VHL
9MP:00053977.7VHL, FOS, SRF, JUNB, HIF1A
10MP:00053877.6VHL, FOS, SRF, JUNB, HIF1A
11MP:00053847.4VHL, FH, FOS, SRF, JUNB, HIF1A
12MP:00053767.4HIF1A, JUNB, SRF, FOS, FH, VHL
13MP:00107687.3HIF1A, JUNB, SRF, FOS, FH, VHL

Publications for Fumarate Hydratase Deficiency

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Articles related to Fumarate Hydratase Deficiency:

(show all 18)
idTitleAuthorsYear
1
Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer. (23633457)
2013
2
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. (23499446)
2013
3
A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer. (22867999)
2012
4
The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. (21907923)
2011
5
Structural basis of fumarate hydratase deficiency. (21445611)
2011
6
Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism. (20660115)
2010
7
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. (20978192)
2010
8
UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer. (19963135)
2010
9
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. (19151755)
2009
10
Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species. (19470762)
2009
11
Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? (17418405)
2007
12
Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. (16319128)
2006
13
Fumarate hydratase deficiency in monozygotic twins. (16876016)
2006
14
Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. (12761039)
2003
15
Fumarate hydratase deficiency: increased fumaric acid in amniotic fluid of two affected pregnancies. (11117439)
2000
16
Fumarate hydratase deficiency. (9700607)
1998
17
Fumarate Hydratase Deficiency (20301679)
1993
18
Variability of clinical presentation in fumarate hydratase deficiency. (1432428)
1992

Variations for Fumarate Hydratase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Fumarate Hydratase Deficiency:

64
id Symbol AA change Variation ID SNP ID
1FHp.Lys230ArgVAR_002445
2FHp.Ala308ThrVAR_002446
3FHp.Phe312CysVAR_002447
4FHp.Asp425ValVAR_002448

Clinvar genetic disease variations for Fumarate Hydratase Deficiency:

6
id Gene Name Type Significance SNP ID Assembly Location
1FHNM_000143.3(FH): c.793G> A (p.Ala265Thr)single nucleotide variantPathogenicrs387906545GRCh37Chr 1, 241669414: 241669414
2FHNM_000143.3(FH): c.1084G> C (p.Glu362Gln)single nucleotide variantPathogenicrs121913119GRCh37Chr 1, 241667366: 241667366
3FHNM_000143.3(FH): c.521C> G (p.Pro174Arg)single nucleotide variantPathogenicrs199822819GRCh37Chr 1, 241675301: 241675301
4FHFH, DELdeletionPathogenic
5FHNM_000143.3(FH): c.1127A> C (p.Gln376Pro)single nucleotide variantPathogenicrs200796606GRCh37Chr 1, 241665852: 241665852
6FHNM_000143.3(FH): c.1431_1433dupAAA (p.Lys477_Asn478insLys)duplicationPathogenicrs367543046GRCh37Chr 1, 241661228: 241661230

Expression for genes affiliated with Fumarate Hydratase Deficiency

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Expression patterns in normal tissues for genes affiliated with Fumarate Hydratase Deficiency

Search GEO for disease gene expression data for Fumarate Hydratase Deficiency.

Pathways for genes affiliated with Fumarate Hydratase Deficiency

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Pathways related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show all 40)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.4SRF, FOS
29.4FOS, SRF
39.4SRF, FOS
49.4FOS, SRF
59.4FOS, SRF
6
Show member pathways
9.4SRF, FOS
7
Show member pathways
9.4FOS, SRF
89.4HIF1A, VHL
9
Show member pathways
VEGFR1 specific signals37
9.4VHL, HIF1A
109.4VHL, HIF1A
119.4HIF1A, VHL
129.4HIF1A, VHL
13
Show member pathways
9.4VHL, HIF1A
14
Show member pathways
Development Ligand dependent activation of the ESR1 AP 1 pathway60
9.3FOS, HIF1A
15
Show member pathways
9.3FOS, HIF1A
169.3HIF1A, FOS
17
Show member pathways
9.3FOS, HIF1A
18
Show member pathways
Immune response IL 3 activation and signaling pathway60
9.1FOS, JUNB
19
Show member pathways
9.1FOS, JUNB
20
Show member pathways
Immune response MIF in innate immunity response60
9.1FOS, JUNB
219.1FOS, JUNB
229.1JUNB, FOS
23
Show member pathways
MAPK Cascade37
Immune response Oncostatin M signaling via MAPK in human cells60
Oncostatin M Signaling Pathway37
9.1FOS, JUNB
249.1JUNB, FOS
259.1FOS, JUNB
26
Show member pathways
Ras signaling in the CD4+ TCR pathway37
9.1FOS, JUNB
27
Show member pathways
9.1FOS, JUNB
289.1FOS, JUNB
299.1JUNB, FOS
309.1FOS, JUNB
31
Show member pathways
Calcium signaling in the CD4+ TCR pathway37
9.1JUNB, FOS
32
Show member pathways
IL27-mediated signaling events37
9.1JUNB, FOS
339.1JUNB, FOS
349.0HIF1A, FH, VHL
35
Show member pathways
8.9HIF1A, FOS, VHL
36
Show member pathways
8.6FOS, SRF, JUNB
37
Show member pathways
8.6FOS, SRF, JUNB
38
Show member pathways
Transcription Receptor mediated HIF regulation60
Development CNTF receptor signaling60
Class IB PI3K non-lipid kinase events37
ErbB2/ErbB3 signaling events37
Development Growth hormone signaling via PI3K AKT and MAPK cascades60
Translation Regulation activity of EIF260
Regulation of lipid metabolism Insulin signaling generic cascades60
Transcription PPAR Pathway60
Cell adhesion PLAU signaling60
Translation Regulation activity of EIF4F60
8.5HIF1A, JUNB, FOS
398.5VHL, FH, FOS, HIF1A
40
Show member pathways
7.5HIF1A, JUNB, SRF, FOS, VHL

Compounds for genes affiliated with Fumarate Hydratase Deficiency

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Compounds related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show top 50)    (show all 65)
idCompoundScoreTop Affiliating Genes
1pilocarpine44 28 1111.8FOS, SRF
2cocl2449.8VHL, HIF1A
3cobalt chloride449.8HIF1A, VHL
4sunitinib44 50 1111.7VHL, HIF1A
5deferoxamine44 1110.7HIF1A, VHL
6cobalt44 2410.6VHL, HIF1A
7bapta449.6FOS, HIF1A
8sch 39166449.6FOS, JUNB
9sch 23390449.5FOS, JUNB
10dizocilpine449.5FOS, JUNB
11fumarate44 1110.4VHL, FH, HIF1A
12alpha-ketoglutarate449.4HIF1A, FH, VHL
13succinate449.4VHL, FH, HIF1A
14naloxone44 28 50 1112.3FOS, JUNB
15agar449.2FOS, SRF, HIF1A
16ly294002449.2HIF1A, FOS, VHL
17amphetamine44 50 1111.1JUNB, FOS
18lactate449.1HIF1A, SRF, FH
19iron44 2410.1VHL, SRF, HIF1A
20superoxide44 2410.0HIF1A, SRF, FH
21capsaicin44 2810.0FOS, HIF1A
22ionomycin449.0FOS, SRF, JUNB
2312-o-tetradecanoylphorbol 13-acetate449.0FOS, SRF, JUNB
24nmda44 289.9JUNB, SRF, FOS
25forskolin44 50 1110.9JUNB, SRF, FOS
26proline448.9HIF1A, SRF, FH, VHL
27arachidonic acid44 28 24 1111.9FOS, SRF, JUNB
28thymidine44 249.9FOS, SRF, HIF1A
29sb 20358044 619.9FOS, JUNB, HIF1A
30tamoxifen44 50 28 1111.8HIF1A, JUNB, FOS
31oxygen44 249.8HIF1A, SRF, FH, VHL
32pd 98,059448.8FOS, JUNB, HIF1A
33vegf448.7HIF1A, SRF, FOS, VHL
34cyclosporin a44 28 6110.7HIF1A, JUNB, SRF
35cyclic amp44 249.6FOS, SRF, JUNB
36leucine448.5FOS, SRF, JUNB
37actinomycin d448.5VHL, FOS, JUNB, HIF1A
38atp44 289.5HIF1A, JUNB, SRF, FH
39genistein44 28 61 2 24 1113.4HIF1A, JUNB, SRF, FOS
40pge2448.4HIF1A, JUNB, SRF, FOS
41cycloheximide448.4HIF1A, JUNB, SRF, FOS
42dexamethasone44 50 28 1111.4HIF1A, JUNB, SRF, FOS
43threonine448.4HIF1A, JUNB, SRF, FOS
44retinoic acid44 249.3FOS, SRF, JUNB, HIF1A
45glucose448.1HIF1A, JUNB, SRF, FH, VHL
46oligonucleotide448.0HIF1A, JUNB, SRF, FOS, VHL
47phosphatidylinositol448.0VHL, FOS, SRF, JUNB, HIF1A
48estrogen448.0HIF1A, JUNB, SRF, FOS, VHL
49serine447.9HIF1A, JUNB, SRF, FOS, VHL
50tyrosine447.6HIF1A, JUNB, SRF, FOS, FH, VHL

GO Terms for genes affiliated with Fumarate Hydratase Deficiency

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Cellular components related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nucleoplasmGO:0056548.0VHL, FOS, JUNB, HIF1A
2nucleolusGO:0057307.8HIF1A, JUNB, FOS, VHL
3nucleusGO:0056347.5VHL, FOS, SRF, JUNB, HIF1A

Biological processes related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show all 18)
idNameGO IDScoreTop Affiliating Genes
1regulation of transcription from RNA polymerase II promoter in response to hypoxiaGO:0614189.6HIF1A, VHL
2mRNA transcription from RNA polymerase II promoterGO:0427899.6SRF, HIF1A
3muscle cell cellular homeostasisGO:0467169.6HIF1A, SRF
4response to light stimulusGO:0094169.4JUNB, FOS
5heart loopingGO:0019479.4HIF1A, SRF
6cellular response to hypoxiaGO:0714569.4VHL, HIF1A
7trophectodermal cell differentiationGO:0018299.4JUNB, SRF
8response to corticosteroneGO:0514129.4FOS, JUNB
9cellular response to hormone stimulusGO:0328709.3FOS, JUNB
10response to progesteroneGO:0325709.3FOS, JUNB
11cellular response to calcium ionGO:0712779.3JUNB, FOS
12response to cAMPGO:0515919.2FOS, JUNB
13response to mechanical stimulusGO:0096129.1FOS, JUNB
14response to toxic substanceGO:0096369.1FOS, SRF
15positive regulation of cell differentiationGO:0455979.0VHL, SRF, JUNB
16response to cytokineGO:0340978.9JUNB, SRF, FOS
17positive regulation of transcription, DNA-templatedGO:0458938.8HIF1A, FOS, VHL
18positive regulation of transcription from RNA polymerase II promoterGO:0459448.3FOS, SRF, JUNB, HIF1A

Molecular functions related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1RNA polymerase II transcription factor binding transcription factor activityGO:0010769.4SRF, HIF1A
2RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptionGO:0010779.2SRF, HIF1A
3double-stranded DNA bindingGO:0036909.1FOS, JUNB
4RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:0037059.0SRF, HIF1A
5transcription factor bindingGO:0081348.5VHL, FOS, SRF, HIF1A
6sequence-specific DNA binding transcription factor activityGO:0037008.0HIF1A, JUNB, SRF, FOS

Products for genes affiliated with Fumarate Hydratase Deficiency

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Sources for Fumarate Hydratase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet