FMRD
MCID: FMR004
MIFTS: 38

Fumarase Deficiency (FMRD) malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Fumarase Deficiency

Aliases & Descriptions for Fumarase Deficiency:

Name: Fumarase Deficiency 54 50 25 56 66 29 13 52 69
Fumaric Aciduria 50 25 56 66 69
Fumarate Hydratase Deficiency 50 25
Fmrd 66

Characteristics:

Orphanet epidemiological data:

56
fumaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

HPO:

32
fumarase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 606812
Orphanet 56 ORPHA24
MESH via Orphanet 43 C538191
ICD10 via Orphanet 34 E88.8
UMLS via Orphanet 70 C0342770 C2936826

Summaries for Fumarase Deficiency

Genetics Home Reference : 25 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 : Fumarase Deficiency, also known as fumaric aciduria, is related to fumarate hydratase deficiency and encephalopathy, and has symptoms including hypertelorism, agenesis of corpus callosum and frontal bossing. An important gene associated with Fumarase Deficiency is FH (Fumarate Hydratase). The drugs Everolimus and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and liver.

NIH Rare Diseases : 50 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

OMIM : 54 Fumarase deficiency is a severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound... (606812) more...

UniProtKB/Swiss-Prot : 66 Fumarase deficiency: A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy.

Wikipedia : 71 Fumarase deficiency (or fumaric aciduria), also known as \"Polygamist Down\'s\", is an autosomal... more...

Related Diseases for Fumarase Deficiency

Diseases related to Fumarase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 fumarate hydratase deficiency 11.1
2 encephalopathy 10.0
3 biliary atresia 9.8
4 cerebritis 9.8
5 tuberculosis 9.8
6 polyhydramnios 9.8
7 mitochondrial encephalomyopathy 9.8
8 encephalomyopathy 9.8
9 hypotonia 9.8

Graphical network of the top 20 diseases related to Fumarase Deficiency:



Diseases related to Fumarase Deficiency

Symptoms & Phenotypes for Fumarase Deficiency

Symptoms by clinical synopsis from OMIM:

606812

Clinical features from OMIM:

606812

Human phenotypes related to Fumarase Deficiency:

32 (show all 30)
id Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 agenesis of corpus callosum 32 HP:0001274
3 frontal bossing 32 HP:0002007
4 high palate 32 HP:0000218
5 muscular hypotonia 32 HP:0001252
6 failure to thrive 32 HP:0001508
7 neurological speech impairment 32 HP:0002167
8 global developmental delay 32 HP:0001263
9 depressed nasal bridge 32 HP:0005280
10 microcephaly 32 HP:0000252
11 anteverted nares 32 HP:0000463
12 visual impairment 32 HP:0000505
13 optic atrophy 32 HP:0000648
14 aminoaciduria 32 HP:0003355
15 pallor 32 HP:0000980
16 lactic acidosis 32 HP:0003128
17 cholestasis 32 HP:0001396
18 intellectual disability, profound 32 HP:0002187
19 hepatic failure 32 HP:0001399
20 metabolic acidosis 32 HP:0001942
21 polymicrogyria 32 HP:0002126
22 status epilepticus 32 HP:0002133
23 cerebral atrophy 32 HP:0002059
24 reduced subcutaneous adipose tissue 32 HP:0003758
25 cutaneous leiomyoma 32 HP:0007620
26 polycythemia 32 HP:0001901
27 hypoplasia of the brainstem 32 HP:0002365
28 relative macrocephaly 32 HP:0004482
29 choroid plexus cyst 32 HP:0002190
30 open operculum 32 HP:0100954

UMLS symptoms related to Fumarase Deficiency:


seizures

Drugs & Therapeutics for Fumarase Deficiency

Drugs for Fumarase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Everolimus Approved Phase 1 159351-69-6 6442177
2
Miconazole Approved, Investigational, Vet_approved Phase 1 22916-47-8 4189
3
Paclitaxel Approved, Vet_approved Phase 1 33069-62-4 36314
4
Sirolimus Approved, Investigational Phase 1 53123-88-9 5284616 6436030 46835353
5
Docetaxel Approved May 1996, Investigational Phase 1 114977-28-5 148124 9877265
6 Albumin-Bound Paclitaxel Phase 1
7 Anti-Bacterial Agents Phase 1
8 Antibiotics, Antitubercular Phase 1
9 Antifungal Agents Phase 1
10 Anti-Infective Agents Phase 1
11 Antimitotic Agents Phase 1
12 Antineoplastic Agents, Phytogenic Phase 1
13 Immunosuppressive Agents Phase 1
14 glutamine Nutraceutical Phase 1

Interventional clinical trials:


id Name Status NCT ID Phase
1 Study of the Glutaminase Inhibitor CB-839 in Solid Tumors Recruiting NCT02071862 Phase 1

Search NIH Clinical Center for Fumarase Deficiency

Genetic Tests for Fumarase Deficiency

Genetic tests related to Fumarase Deficiency:

id Genetic test Affiliating Genes
1 Fumarase Deficiency 29

Anatomical Context for Fumarase Deficiency

MalaCards organs/tissues related to Fumarase Deficiency:

39
Brain, Eye, Liver, Spleen

Publications for Fumarase Deficiency

Articles related to Fumarase Deficiency:

(show all 26)
id Title Authors Year
1
Fumarase Deficiency Causes Protein and Metabolite Succination and Intoxicates Mycobacterium tuberculosis. ( 28219662 )
2017
2
Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer. ( 27541980 )
2016
3
Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene. ( 23612258 )
2013
4
Infantile metabolic encephalopathy due to fumarase deficiency. ( 22772160 )
2013
5
Fumarase deficiency in dichorionic diamniotic twins. ( 24182348 )
2013
6
Fumarase Deficiency Associated With Non-Inflammatory Biliary Atresia. ( 22922375 )
2012
7
Mild fumarase deficiency and a trial of low protein diet. ( 22595425 )
2012
8
Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency. ( 22069215 )
2012
9
Clinical and biochemical heterogeneity associated with fumarase deficiency. ( 21560188 )
2011
10
The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. ( 18366737 )
2008
11
Molecular and biochemical investigations in fumarase deficiency. ( 16510303 )
2006
12
Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1. ( 16575891 )
2006
13
Fumarase deficiency presenting with periventricular cysts. ( 16151915 )
2005
14
A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency. ( 15221078 )
2004
15
[Fumarase deficiency]. ( 12013993 )
2002
16
[Fumarase deficiency]. ( 11596337 )
2001
17
Abnormalities in succinylpurines in fumarase deficiency: possible role in pathogenesis of CNS impairment. ( 10896297 )
2000
18
[Fumarase deficiency]. ( 9590067 )
1998
19
Molecular analysis and prenatal diagnosis of human fumarase deficiency. ( 9635293 )
1998
20
Congenital fumarase deficiency presenting with hypotonia and areflexia. ( 8734035 )
1996
21
Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency. ( 8200987 )
1994
22
Fumarase deficiency: two siblings with enlarged cerebral ventricles and polyhydramnios in utero. ( 1557269 )
1992
23
Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes. ( 2314594 )
1990
24
A fourth case of fumarase deficiency. ( 2515378 )
1989
25
Fumarase deficiency. ( 3807970 )
1987
26
Fumarase deficiency: a new cause of mitochondrial encephalomyopathy. ( 3736629 )
1986

Variations for Fumarase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Fumarase Deficiency:

66
id Symbol AA change Variation ID SNP ID
1 FH p.Lys230Arg VAR_002445 rs752232718
2 FH p.Ala308Thr VAR_002446 rs121913118
3 FH p.Phe312Cys VAR_002447
4 FH p.Asp425Val VAR_002448

ClinVar genetic disease variations for Fumarase Deficiency:

6 (show all 27)
id Gene Variation Type Significance SNP ID Assembly Location
1 FH NM_000143.3(FH): c.793G> A (p.Ala265Thr) single nucleotide variant Pathogenic rs387906545 GRCh37 Chromosome 1, 241669414: 241669414
2 FH NM_000143.3(FH): c.1084G> C (p.Glu362Gln) single nucleotide variant Pathogenic rs121913119 GRCh37 Chromosome 1, 241667366: 241667366
3 FH NM_000143.3(FH): c.698G> A (p.Arg233His) single nucleotide variant Pathogenic rs121913123 GRCh37 Chromosome 1, 241671943: 241671943
4 FH FH, DEL deletion Pathogenic
5 FH NM_000143.3(FH): c.1255T> C (p.Ser419Pro) single nucleotide variant Pathogenic/Likely pathogenic rs200004220 GRCh37 Chromosome 1, 241663872: 241663872
6 FH NM_000143.3(FH): c.1293delA (p.Glu432Lysfs) deletion Pathogenic rs398123163 GRCh37 Chromosome 1, 241663834: 241663834
7 FH NM_000143.3(FH): c.912_918delTTTTGTC (p.Phe305Leufs) deletion Pathogenic rs794727836 GRCh37 Chromosome 1, 241667532: 241667538
8 FH NM_000143.3(FH): c.1430_1437dupAAAATGGA (p.Ser480Lysfs) duplication Pathogenic rs863223994 GRCh37 Chromosome 1, 241661224: 241661231
9 FH NM_000143.3(FH): c.1370_1371insTCAC (p.Ala458Hisfs) insertion Pathogenic/Likely pathogenic rs863223992 GRCh38 Chromosome 1, 241500456: 241500457
10 FH NM_000143.3(FH): c.1189G> A (p.Gly397Arg) single nucleotide variant Pathogenic rs863224007 GRCh38 Chromosome 1, 241502490: 241502490
11 FH NM_000143.3(FH): c.1097G> A (p.Ser366Asn) single nucleotide variant Pathogenic/Likely pathogenic rs863224004 GRCh37 Chromosome 1, 241667353: 241667353
12 FH NM_000143.3(FH): c.1083_1086delTGAA (p.Glu362Glnfs) deletion Pathogenic rs756469140 GRCh37 Chromosome 1, 241667364: 241667367
13 FH NM_000143.3(FH): c.267+1G> C single nucleotide variant Pathogenic rs878853691 GRCh37 Chromosome 1, 241680481: 241680481
14 FH NC_000001.11: g.(?_241497557)_(241504245_?)del deletion Pathogenic GRCh37 Chromosome 1, 241660857: 241667545
15 FH NC_000001.11: g.(?_241497557)_(241519785_?)del deletion Pathogenic GRCh38 Chromosome 1, 241497557: 241519785
16 FH NM_000143.3(FH): c.1391-1G> A single nucleotide variant Likely pathogenic rs863223978 GRCh38 Chromosome 1, 241497971: 241497971
17 FH NM_000143.3(FH): c.1112delA (p.Lys371Argfs) deletion Pathogenic rs1060500904 GRCh38 Chromosome 1, 241502567: 241502567
18 FH NM_000143.3(FH): c.1052C> A (p.Ser351Ter) single nucleotide variant Pathogenic rs1060500896 GRCh38 Chromosome 1, 241504098: 241504098
19 FH NM_000143.3(FH): c.1021G> A (p.Asp341Asn) single nucleotide variant Likely pathogenic rs11545655 GRCh38 Chromosome 1, 241504129: 241504129
20 FH NM_000143.3(FH): c.738+2T> C single nucleotide variant Likely pathogenic rs1060500901 GRCh38 Chromosome 1, 241508601: 241508601
21 FH NM_000143.3(FH): c.267+1G> A single nucleotide variant Pathogenic rs878853691 GRCh38 Chromosome 1, 241517181: 241517181
22 FH NM_000143.3(FH): c.1157A> G (p.Gln386Arg) single nucleotide variant Likely pathogenic rs750447792 GRCh38 Chromosome 1, 241502522: 241502522
23 FH NM_000143.3(FH): c.679C> T (p.Gln227Ter) single nucleotide variant Pathogenic rs11545658 GRCh38 Chromosome 1, 241508662: 241508662
24 FH NM_000143.3(FH): c.204T> A (p.Tyr68Ter) single nucleotide variant Pathogenic rs1060500883 GRCh38 Chromosome 1, 241517245: 241517245
25 FH NM_000143.3(FH): c.1484_1488delAGCAG (p.Glu495Valfs) deletion Likely pathogenic rs1060500907 GRCh38 Chromosome 1, 241497873: 241497877
26 FH NM_000143.3(FH): c.1347delG (p.Met449Ilefs) deletion Pathogenic rs1060500903 GRCh38 Chromosome 1, 241500480: 241500480
27 FH NM_000143.3(FH): c.560C> A (p.Ser187Ter) single nucleotide variant Pathogenic rs398123166 GRCh38 Chromosome 1, 241508781: 241508781

Copy number variations for Fumarase Deficiency from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 28402 1 222100000 228800000 Copy number FH Fumarase deficiency

Expression for Fumarase Deficiency

Search GEO for disease gene expression data for Fumarase Deficiency.

Pathways for Fumarase Deficiency

GO Terms for Fumarase Deficiency

Sources for Fumarase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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