MCID: BRT005
MIFTS: 58

Barth Syndrome malady

Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases, Blood diseases, Cardiovascular diseases categories

Summaries for Barth Syndrome

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NINDS:42 Barth syndrome (BTHS) is a rare, genetic disorder of lipid metabolism that primarily affects males. It is caused by a mutation in the tafazzin gene (TAZ, also called G4.5) which leads to decreased production of an enzyme required to produce cardiolipin. Cardiolipin is an essential lipid that is important in energy metabolism. BTHS, which affects multiple body systems, is considered serious. Its main characteristics often include combinations in varying degrees of cardiomyopathy (a disorder of the heart muscle leading to a poorly functioning heart), neutropenia (a reduction in the number of white blood cells which may lead to an increased risk for bacterial infections), hypotonia (reduced muscle tone), muscle weakness, undeveloped skeletal muscles, delayed growth, lack of stamina, varying degrees of physical disability, and methylglutaconic aciduria (an increase in an organic acid that results in abnormal mitochondria function). Although some with BTHS may have all of these characteristics, others may have only one or two, and, thus, are often misdiagnosed. BTHS is an X-linked genetic condition passed from mother to son through the X chromosome. A mother who is a carrier of BTHS shows no signs or symptoms of the disorder herself. On average, 50 percent of children born to a carrier mother will inherit the defective gene, but only boys will develop symptoms. All daughters born to an affected male will be carriers.

MalaCards based summary: Barth Syndrome, also known as 3-methylglutaconic aciduria type 2, is related to myopathy and dilated cardiomyopathy, and has symptoms including hypertrophic cardiomyopathy, abnormality of neutrophils and abnormality of the musculature. An important gene associated with Barth Syndrome is TAZ (tafazzin), and among its related pathways are Muscular Dystrophies and Dystrophin-Glycoprotein Complex and Mitochondrial Protein Import. The compounds 7beta-hydroxycholesterol and lysophospholipid have been mentioned in the context of this disorder. Affiliated tissues include heart, skeletal muscle and neutrophil, and related mouse phenotypes are muscle and growth/size/body.

Disease Ontology:9 A lipid metabolism disorder that has material basis in x-linked inheritance of the tafazzin gene and is characterized by decreased production of an enzyme required to produce cardiolipin.

NIH Rare Diseases:41 Barth syndrome is a metabolic and neuromuscular disorder, occurring exclusively in males, that primarily affects the heart, immune system, and growth. it typically becomes apparent during infancy or early childhood, but the age of onset, associated symptoms and findings, and disease course varies considerably among affected individuals. the main characteristics of the condition include abnormalities of heart and skeletal muscle (cardiomyopathy and skeletal myopathy); low levels of certain white blood cells called neutrophils that help to fight bacterial infections (neutropenia); and growth retardation, potentially leading to short stature. other signs and symptoms may include increased levels of certain organic acids in the urine and blood (such as 3-methylglutaconic acid), and increased thickness of the left ventricle of the heart due to endocardial fibroelastosis, which can cause potential heart failure. it is caused by mutations in the taz gene and is inherited in an x-linked recessive manner. treatment is directed toward the specific symptoms that are apparent in each individual. last updated: 6/3/2011

Genetics Home Reference:21 Barth syndrome is a rare condition characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small numbers of white blood cells (neutropenia), and short stature. Barth syndrome occurs almost exclusively in males.

OMIM:45 Barth syndrome (BTHS) is an X-linked disease conventionally characterized by dilated cardiomyopathy (CMD) with... (302060) more...

Wikipedia:63 Barth syndrome (BTHS), also known as 3-Methylglutaconic aciduria type II, is an X-linkedgenetic... more...

GeneReviews summary for barth

Aliases & Classifications for Barth Syndrome

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Sources:
45OMIM, 9Disease Ontology, 10diseasecard, 19GeneReviews, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 42NINDS, 11DISEASES, 43Novoseek, 47Orphanet, 22GTR, 60UMLS, 33MeSH, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Barth Syndrome, Aliases & Descriptions:

Name: Barth Syndrome 45 9 10 19 41 21 42 11 43 47
3-Methylglutaconic Aciduria Type 2 41 21 47 60
Cardioskeletal Myopathy with Neutropenia and Abnormal Mitochondria 41 21 47
Mga Type Ii 9 41 21
Bths 41 21 47
X-Linked Cardioskeletal Myopathy and Neutropenia 41 47
3 Methylglutaconic Aciduria, Type Ii 21 22
3-Methylglutaconic Aciduria Type Ii 41 20
 
Cardioskeletal Myopathy-Neutropenia 41 47
Mga Type 2 9 21
Mga2 41 47
3-Methylglutaconicaciduria Type Ii 9
3-Methylglutaconicaciduria Type 2 9
Dnajc19 Defect 21
Taz Defect 21


Classifications:



Characteristics (Orphanet epidemiological data):

47
barth syndrome:
Inheritance: X-linked recessive; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (United States),1-9/1000000 (United Kingdom); Age of onset: Childhood; Age of death: any age


External Ids:

OMIM45 302060
Disease Ontology9 DOID:0050476
MeSH33 D056889
Orphanet47 111
MESH via Orphanet34 D056889
ICD10 via Orphanet26 E71.1
UMLS via Orphanet61 C0574083

Related Diseases for Barth Syndrome

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Graphical network of diseases related to Barth Syndrome:



Diseases related to barth syndrome

Symptoms for Barth Syndrome

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Symptoms by clinical synopsis from OMIM:

302060

Clinical features from OMIM:

302060

Symptoms:

 47
  • cardiomyopathy/hypertrophic/dilated
  • x-linked recessive inheritance
  • endocardium anomalies/fibroelastosis/endocarditis
  • abnormal muscle biopsy/muscle enzymes/cpk/ldh/aldolase/creatin phosphokinase
  • polynuclear cells/neutrophils anomalies/neutropenia

HPO human phenotypes related to Barth Syndrome:

(show all 29)
id Description Frequency HPO Source Accession
1 hypertrophic cardiomyopathy hallmark (90%) HP:0001639
2 abnormality of neutrophils typical (50%) HP:0001874
3 abnormality of the musculature typical (50%) HP:0003011
4 abnormality of the endocardium typical (50%) HP:0004306
5 talipes equinovarus rare (5%) HP:0001762
6 neutropenia rare (5%) HP:0001875
7 full cheeks HP:0000293
8 mandibular prognathia HP:0000303
9 round face HP:0000311
10 macrotia HP:0000400
11 deeply set eye HP:0000490
12 motor delay HP:0001270
13 gait disturbance HP:0001288
14 x-linked recessive inheritance HP:0001419
15 failure to thrive HP:0001508
16 growth delay HP:0001510
17 congestive heart failure HP:0001635
18 hypertrophic cardiomyopathy HP:0001639
19 dilated cardiomyopathy HP:0001644
20 endocardial fibroelastosis HP:0001706
21 granulocytopenia HP:0001913
22 myopathic facies HP:0002058
23 exercise intolerance HP:0003546
24 skeletal myopathy HP:0003756
25 intermittent lactic acidemia HP:0004913
26 recurrent infections in infancy and early childhood HP:0005437
27 abnormal mitochondrial morphology HP:0008322
28 arrhythmia HP:0011675
29 fatigue HP:0012378

Drugs & Therapeutics for Barth Syndrome

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Drug clinical trials:

Search ClinicalTrials for Barth Syndrome

Search NIH Clinical Center for Barth Syndrome

Genetic Tests for Barth Syndrome

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Genetic tests related to Barth Syndrome:

id Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria Type 220 22 TAZ

Anatomical Context for Barth Syndrome

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MalaCards organs/tissues related to Barth Syndrome:

31
Heart, Skeletal muscle, Neutrophil, Eye, Skin, Testes, Pituitary

Animal Models for Barth Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Barth Syndrome:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053698.1DMD, WWTR1, DTNA, LDB3, PLA2G6, PDLIM5
2MP:00053787.3DMD, WWTR1, DTNA, LDB3, PLA2G6, LCLAT1
3MP:00107687.2ZBTB18, DMD, DBT, WWTR1, DTNA, LDB3
4MP:00053866.5PDLIM5, DMD, DBT, WWTR1, DTNA, LDB3

Publications for Barth Syndrome

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Articles related to Barth Syndrome:

(show top 50)    (show all 128)
idTitleAuthorsYear
1
A Novel TAZ Gene Mutation and Mosaicism in a Polish Family with Barth Syndrome. (25776009)
2015
2
The mitochondrial quality control protein yme1 is necessary to prevent defective mitophagy in a yeast model of barth syndrome. (25688091)
2015
3
Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome. (25782672)
2015
4
Your heart on a chip: iPSC-based modeling of Barth-syndrome-associated cardiomyopathy. (24996164)
2014
5
Pharmacogenomic considerations in the treatment of the pediatric cardiomyopathy called Barth syndrome. (25185984)
2014
6
Clinical laboratory studies in Barth Syndrome. (24751896)
2014
7
The functions of cardiolipin in cellular metabolism-potential modifiers of the Barth syndrome phenotype. (24445246)
2014
8
Barth syndrome. (23843353)
2013
9
Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. (23523468)
2013
10
New clinical and molecular insights on Barth syndrome. (23409742)
2013
11
Successful mechanical circulatory support for 251 days in a child with intermittent severe neutropenia due to Barth syndrome. (23190323)
2013
12
Barth syndrome in a female patient. (22410210)
2012
13
The Barth Syndrome Registry: distinguishing disease characteristics and growth data from a longitudinal study. (23045169)
2012
14
The cellular and molecular mechanisms for neutropenia in Barth syndrome. (22023389)
2012
15
Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. (21068380)
2011
16
Eponym: Barth syndrome. (21947198)
2011
17
Impaired cardiac reserve and severely diminished skeletal muscle Oa88 utilization mediate exercise intolerance in Barth syndrome. (21873497)
2011
18
Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth. (20812380)
2010
19
Dysmorphology of Barth syndrome. (19648820)
2009
20
Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome. (19962311)
2009
21
Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome. (19164547)
2009
22
Psychosocial Functioning in Youth with Barth Syndrome. (20808735)
2009
23
The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. (18799610)
2008
24
Mitral annuloplasty in an infant with Barth syndrome and severe mitral insufficiency: first case report and determination of annular diameter. (18954662)
2008
25
Cardiomyopathy of unknown etiology: Barth syndrome unrecognized. (19037987)
2008
26
Prevalence of Barth syndrome in adult left ventricular hypertrabeculation / noncompaction. (18365900)
2008
27
Gene symbol: TAZ. Disease: Barth syndrome. (18846664)
2008
28
New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. (16904369)
2007
29
Barth syndrome is associated with a cognitive phenotype. (17353728)
2007
30
Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition. (16055927)
2006
31
Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins. (16880272)
2006
32
A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function. (16794186)
2006
33
Barth syndrome presenting with acute metabolic decompensation in the neonatal period. (16906470)
2006
34
A Drosophila model of Barth syndrome. (16855048)
2006
35
Cardiac and clinical phenotype in Barth syndrome. (16847078)
2006
36
Barth syndrome without 3-methylglutaconic aciduria. (15124852)
2004
37
The human TAZ gene complements mitochondrial dysfunction in the yeast taz1Delta mutant. Implications for Barth syndrome. (15304507)
2004
38
Linoleic acid supplementation of Barth syndrome fibroblasts restores cardiolipin levels: implications for treatment. (12562862)
2003
39
Normal pituitary function in a Japanese patient with Barth syndrome. (11808885)
2002
40
Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. (12112112)
2002
41
Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): a study in cultured skin fibroblasts. (12410207)
2002
42
Quantitative and compositional study of cardiolipin in platelets by electrospray ionization mass spectrometry: application for the identification of Barth syndrome patients. (12194913)
2002
43
Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. (11238270)
2001
44
Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome. (11118295)
2000
45
X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)-MIM 302060. (10484787)
1999
46
X chromosome inactivation in carriers of Barth syndrome. (9792874)
1998
47
Barth syndrome may be due to an acyltransferase deficiency. (9259571)
1997
48
Mutation characterization and genotype-phenotype correlation in Barth syndrome. (9345098)
1997
49
Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28. (8434619)
1993
50
Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. (1998334)
1991

Variations for Barth Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Barth Syndrome:

62
id Symbol AA change Variation ID SNP ID
1TAZp.Arg94SerVAR_014110
2TAZp.Cys118ArgVAR_014111
3TAZp.Gly197ArgVAR_014112
4TAZp.Gly240ArgVAR_068434

Clinvar genetic disease variations for Barth Syndrome:

6 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1TAZTAZ, IVS2, G-A, -1single nucleotide variantPathogenic
2TAZNM_000116.3(TAZ): c.153C> G (p.Tyr51Ter)single nucleotide variantPathogenicrs104894941GRCh37Chr X, 153640466: 153640466
3TAZTAZ, IVS2, G-C, -1single nucleotide variantPathogenic
4TAZTAZ, 1-BP INSinsertionPathogenic
5TAZTAZ, 1-BP DELdeletionPathogenic
6TAZNM_000116.3(TAZ): c.589G> A (p.Gly197Arg)single nucleotide variantPathogenicrs132630277GRCh37Chr X, 153648376: 153648376
7TAZTAZ, IVS1, G-C, +5single nucleotide variantPathogenic
8TAZTAZ, IVS3, G-A, +110single nucleotide variantPathogenic
9TAZNM_000116.3(TAZ): c.352T> C (p.Cys118Arg)single nucleotide variantPathogenicrs104894937GRCh37Chr X, 153641886: 153641886
10TAZTAZ, IVS1, A-G, -2single nucleotide variantPathogenic
11TAZNM_000116.3(TAZ): c.280C> A (p.Arg94Ser)single nucleotide variantPathogenicrs104894942GRCh37Chr X, 153641585: 153641585
12TAZTAZ, 4-BP DEL, AGTGdeletionPathogenic
13TAZNM_000116.3(TAZ): c.647-1G> Csingle nucleotide variantPathogenicGRCh37Chr X, 153648550: 153648550
14TAZNM_000116.3(TAZ): c.718G> A (p.Gly240Arg)single nucleotide variantPathogenicrs387907218GRCh37Chr X, 153649015: 153649015
15TAZNM_000116.3(TAZ): c.328T> C (p.Ser110Pro)single nucleotide variantLikely pathogenicrs397515739GRCh37Chr X, 153641862: 153641862
16TAZNM_000116.3(TAZ): c.307T> C (p.Cys103Arg)single nucleotide variantLikely pathogenicrs397515740GRCh37Chr X, 153641841: 153641841
17TAZNM_000116.3(TAZ): c.310T> C (p.Phe104Leu)single nucleotide variantPathogenicrs397515741GRCh37Chr X, 153641844: 153641844
18TAZNM_000116.3(TAZ): c.590G> A (p.Gly197Glu)single nucleotide variantLikely pathogenicrs397515746GRCh37Chr X, 153648377: 153648377

Expression for genes affiliated with Barth Syndrome

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Search GEO for disease gene expression data for Barth Syndrome.

Pathways for genes affiliated with Barth Syndrome

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Pathways related to Barth Syndrome according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.7DTNA, DMD
29.3TAZ, DNAJC19, TOMM40, TIMM17A
3
Show member pathways
9.3TAZ, DNAJC19, TOMM40, TIMM17A
4
Show member pathways
9.1PLA2G6, LCLAT1, TAZ
5
Show member pathways
8.1DBT, AMPD1, WWTR1, PLA2G6, LCLAT1, TAZ

Compounds for genes affiliated with Barth Syndrome

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Sources:
43Novoseek, 28IUPHAR, 12DrugBank, 24HMDB, 59Tocris Bioscience
See all sources

Compounds related to Barth Syndrome according to GeneCards Suite gene sharing:

(show all 19)
idCompoundScoreTop Affiliating Genes
17beta-hydroxycholesterol43 2811.2ANXA5, TTR
2lysophospholipid4310.1PLA2G6, DBT
3bromoenol lactone4310.1PLA2G6, ANXA5
4hoechst 333424310.0DMD, ANXA5
5cardiolipin43 1210.9TAZ, PLA2G6, ANXA5
6phosphatidylethanolamine43 1210.9ANXA5, PLA2G6, TAZ
7quinacrine43 1210.9DBT, PLA2G6
8ndga439.8PLA2G6, ANXA5
9lidocaine43 28 1211.7PLA2G6, ANXA5
10phosphatidylcholine439.7TAZ, PLA2G6, ANXA5
11phosphatidylserine43 28 1211.7PLA2G6, ANXA5, TTR
12glycerol43 24 1211.6DMD, TTR, PLA2G6
13lysophosphatidylcholine28 4310.6PLA2G6, DBT
14cyclosporin a43 28 5911.4DMD, TTR, ANXA5, PLA2G6
15adenylate439.4PLA2G6, AMPD1, TTR, DMD
16Heptadecanoyl CoA249.3LCLAT1, PLA2G6, DBT
17phospholipid439.3DMD, DBT, ANXA5, PLA2G6, TAZ
18lipid439.0DMD, DBT, TOMM40, ANXA5, PLA2G6, TAZ
19atp43 289.5TAZ, PLA2G6, ANXA5, TOMM40, AMPD1, TIMM17A

GO Terms for genes affiliated with Barth Syndrome

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Cellular components related to Barth Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1protein complexGO:00432349.4DTNA, TTR, DMD
2mitochondrionGO:00057398.9TAZ, PLA2G6, DNAJC19, TOMM40, DBT

Biological processes related to Barth Syndrome according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1cardiolipin biosynthetic processGO:003204910.0TAZ, PLA2G6
2cardiac muscle contractionGO:00600489.9TAZ, DMD
3response to organic substanceGO:00100339.6ANXA5, AMPD1
4protein targeting to mitochondrionGO:00066269.6DNAJC19, TOMM40, TIMM17A
5cardiolipin acyl-chain remodelingGO:00359659.2TAZ, LCLAT1, PLA2G6
6glycerophospholipid biosynthetic processGO:00464749.1PLA2G6, LCLAT1, TAZ
7phospholipid metabolic processGO:00066449.0TAZ, LCLAT1, PLA2G6

Molecular functions related to Barth Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1protein kinase C bindingGO:00050809.9PDLIM5, LDB3

Products for genes affiliated with Barth Syndrome

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Sources for Barth Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet