ANH1
MCID: XLN006
MIFTS: 62

X-Linked Sideroblastic Anemia (ANH1) malady

Genetic diseases, Rare diseases, Immune diseases, Blood diseases, Bone diseases categories

Summaries for X-Linked Sideroblastic Anemia

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44NIH Rare Diseases, 48OMIM, 34MalaCards
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NIH Rare Diseases:44 X-linked sideroblastic anemia is an inherited disorder that prevents developing red blood cells (erythroblasts) from making enough hemoglobin. people with x-linked sideroblastic anemia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. this disorder also leads to an abnormal accumulation of iron in red blood cells. the iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. these abnormal cells give the condition its name. the signs and symptoms of x-linked sideroblastic anemia result from a combination of reduced hemoglobin and an overload of iron. they range from mild to severe and most often appear in young adulthood. common features include fatigue, dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). over time, severe medical problems such as heart disease and liver damage (cirrhosis) can result from the buildup of excess iron in these organs. x-linked sideroblastic anemia is caused by mutation in the alas2 gene. in rare cases, mutations are found in both the hfe gene and the alas2 gene, resulting in a more severe form of x-linked sideroblastic anemia. x-linked sideroblastic anemia is inherited in an x-linked recessive pattern. last updated: 3/11/2013

MalaCards: X-Linked Sideroblastic Anemia, also known as xlsa, is related to sideroblastic anemia and x-linked sideroblastic anemia with ataxia, and has symptoms including red cell structure/shape anomalies, red cell disorders and structural and functional anomalies of the spleen. An important gene associated with X-Linked Sideroblastic Anemia is ALAS2 (aminolevulinate, delta-, synthase 2), and among its related pathways are Mitochondrial Protein Import and Citric acid cycle (TCA cycle). The drug carboplatin and the compounds ferric ammonium citrate and protoporphyrin ix have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, bone and spleen, and related mouse phenotypes are embryogenesis and mortality/aging.

Description from OMIM:48 300751

Aliases & Classifications for X-Linked Sideroblastic Anemia

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9Disease Ontology, 10diseasecard, 66Wikipedia, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 11DISEASES, 46Novoseek, 50Orphanet, 63UMLS, 60SNOMED-CT via Orphanet, 37MESH via Orphanet, 27ICD10 via Orphanet, 26ICD10
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Classifications:



Characteristics (Orphanet epidemiological data):

50
x-linked sideroblastic anemia:
Inheritance: X-linked recessive; Age of onset: Variable


Aliases & Descriptions:

x-linked sideroblastic anemia 9 66 44 22 50
xlsa 9 66 44 22 50
anemia hereditary sideroblastic 44 21 23
hereditary iron-loading anemia 66 44 22
bone marrow diseases 66 46 63
anh1 66 44 22
erythroid 5-aminolevulinate synthase deficiency 44 22
anemia, sex-linked hypochromic sideroblastic 66 22
x chromosome-linked sideroblastic anemia 44 22
congenital sideroblastic anaemia 66 22
anemia, hereditary sideroblastic 66 22
anemia, sideroblastic, x-linked 10 48
sideroblastic anemia x-linked 44 21
x-linked pyridoxine-responsive sideroblastic anemia 22
erythroid 5-aminolevulinate synthetase deficiency 66
anemia sex-linked hypochromic sideroblastic 44
congenital sideroblastic anemia 44
hereditary sideroblastic anemia 63
anemia congenital sideroblastic 46
bone marrow disease 11
hypochromic anemia 66


External Ids:

Disease Ontology9 DOID:0060063
OMIM48 300751
SNOMED-CT via Orphanet60 25443007, 191260004
MESH via Orphanet37 C536761
ICD10 via Orphanet27 D64.0
ICD1026 D64.0

Related Diseases for X-Linked Sideroblastic Anemia

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18GeneCards, 19GeneDecks
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Graphical network of the top 20 diseases related to X-Linked Sideroblastic Anemia:



Diseases related to x-linked sideroblastic anemia

Symptoms for X-Linked Sideroblastic Anemia

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

300751

Clinical features from OMIM:

300751

Symptoms:

50 (show all 10)
  • red cell structure/shape anomalies
  • red cell disorders
  • structural and functional anomalies of the spleen
  • x-linked recessive inheritance
  • irregular/in bands/reticular skin hyperpigmentation
  • anaemia
  • structural anomalies of the cardio-circulatory system
  • insulin-independent/type 2 diabetes
  • storage liver disease
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction

Drugs & Therapeutics for X-Linked Sideroblastic Anemia

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for X-Linked Sideroblastic Anemia

Drug clinical trials:

Search ClinicalTrials for X-Linked Sideroblastic Anemia

Search NIH Clinical Center for X-Linked Sideroblastic Anemia

Search CenterWatch for X-Linked Sideroblastic Anemia

Inferred drug relations via UMLS63/NDF-RT42:

Genetic Tests for X-Linked Sideroblastic Anemia

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21GeneTests, 23GTR
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Genetic tests related to X-Linked Sideroblastic Anemia:

id Genetic test Affiliating Genes
1 X-Linked Sideroblastic Anemia21 ALAS2
2 Hereditary Sideroblastic Anemia21 23 YARS2

Anatomical Context for X-Linked Sideroblastic Anemia

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34MalaCards
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MalaCards organs/tissues related to X-Linked Sideroblastic Anemia:

34
Bone marrow, Bone, Spleen, Liver, Skin, Heart, Lung

Animal Models for X-Linked Sideroblastic Anemia or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to X-Linked Sideroblastic Anemia:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053808.5FXN, ALAS2, ALAS1, ABCB7
2MP:00107687.1FXN, ABCB7, TFE3, ACO1, ALAS1, ALAS2

Publications for X-Linked Sideroblastic Anemia

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53PubMed
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Articles related to X-Linked Sideroblastic Anemia:

(show all 33)
idTitleAuthorsYear
1
X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. (24166784)
2013
2
X-linked sideroblastic anemia and ataxia: A new family with identification of a fourth ABCB7 gene mutation. (22398176)
2012
3
X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the I^-subunit of succinyl-CoA synthetase (SUCLA2). (22740690)
2012
4
New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine. (21252495)
2011
5
Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. (17192398)
2007
6
X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. (16735131)
2006
7
Onset of X-linked sideroblastic anemia in the fourth decade. (15477213)
2004
8
Construction of recombinant vector expressing ALAS2 gene in X-linked sideroblastic anemia]. (15498136)
2004
9
Iron overload due to X-linked sideroblastic anemia in an African American man. (15047047)
2004
10
A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. (12663458)
2003
11
Late-onset X-linked sideroblastic anemia following hemodialysis. (12531813)
2003
12
Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. (12393718)
2002
13
A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia. (12031592)
2002
14
X chromosome inactivation ratios in female carriers of X-linked sideroblastic anemia. (11405213)
2001
15
A novel mutation of the ALAS2 gene in a family with X-linked sideroblastic anemia]. (11877024)
2000
16
Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron- sulfur protein maturation. (11050011)
2000
17
Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. (11110715)
2000
18
Animal models for X-linked sideroblastic anemia. (11039663)
2000
19
X-linked sideroblastic anemia]. (10483144)
1999
20
Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). (10196363)
1999
21
Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. (10029606)
1999
22
Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. (9621516)
1998
23
Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene. (9226183)
1997
24
A new mutation of the ALAS2 gene in a large family with X-linked sideroblastic anemia. (7705839)
1995
25
Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia. (7592563)
1995
26
Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. (7560104)
1995
27
X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. (7949148)
1994
28
X-Linked Sideroblastic Anemia and Ataxia (20301496)
1993
29
Erythroid 5-aminolevulinate synthase and X-linked sideroblastic anemia. (8089650)
1993
30
Enzymatic defect in 'X-linked' sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. (1570328)
1992
31
Identification of a highly polymorphic marker within intron 7 of the ALAS2 gene and suggestion of at least two loci for X-linked sideroblastic anemia. (1301172)
1992
32
X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13. (1671320)
1991
33
5-Aminolevulinate synthase is at 3p21 and thus not the primary defect in X-linked sideroblastic anemia. (3414687)
1988

Variations for X-Linked Sideroblastic Anemia

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for X-Linked Sideroblastic Anemia:

65 (show all 20)
id Symbol AA change Variation ID SNP ID
1ALAS2p.Thr388SerVAR_000562
2ALAS2p.Arg411CysVAR_000563
3ALAS2p.Ile476AsnVAR_000564
4ALAS2p.Tyr199HisVAR_012334
5ALAS2p.Arg204GlnVAR_012335
6ALAS2p.Arg448GlnVAR_012336
7ALAS2p.Arg452CysVAR_012337
8ALAS2p.Asp159TyrVAR_018604
9ALAS2p.Arg560HisVAR_018605
10ALAS2p.Lys156GluVAR_066232
11ALAS2p.Arg170HisVAR_066233
12ALAS2p.Arg218HisVAR_066234rs185504937
13ALAS2p.Glu242LysVAR_066235
14ALAS2p.Asp263AsnVAR_066236
15ALAS2p.Pro339LeuVAR_066237
16ALAS2p.Arg375CysVAR_066238
17ALAS2p.Arg411HisVAR_066239
18ALAS2p.Arg452GlyVAR_066240
19ALAS2p.Arg452HisVAR_066241
20ALAS2p.Arg572HisVAR_066243

Clinvar genetic disease variations for X-Linked Sideroblastic Anemia:

1 (show all 13)
id Gene Name Type Significance SNP ID Assembly Location
1ALAS2NM_000032.4(ALAS2): c.1427T> A (p.Ile476Asn)single nucleotide variantPathogenicrs137852299GRCh37Chr X, 55041190: 55041190
2ALAS2NM_000032.4(ALAS2): c.1163C> G (p.Thr388Ser)single nucleotide variantPathogenicrs137852300GRCh37Chr X, 55042016: 55042016
3ALAS2NM_000032.4(ALAS2): c.495C> A (p.Phe165Leu)single nucleotide variantPathogenicrs137852301GRCh37Chr X, 55047628: 55047628
4ALAS2NM_000032.4(ALAS2): c.871G> A (p.Gly291Ser)single nucleotide variantPathogenicrs137852302GRCh37Chr X, 55044051: 55044051
5ALAS2NM_000032.4(ALAS2): c.1231C> T (p.Arg411Cys)single nucleotide variantPathogenicrs137852305GRCh37Chr X, 55041386: 55041386
6ALAS2NM_000032.4(ALAS2): c.1702A> G (p.Ser568Gly)single nucleotide variantPathogenicrs137852306GRCh37Chr X, 55035675: 55035675
7ALAS2NM_000032.4(ALAS2): c.1184G> A (p.Cys395Tyr)single nucleotide variantPathogenicrs137852307GRCh37Chr X, 55041433: 55041433
8ALAS2NM_000032.4(ALAS2): c.475G> T (p.Asp159Tyr)single nucleotide variantPathogenicrs137852308GRCh37Chr X, 55047648: 55047648
9ALAS2NM_000032.4(ALAS2): c.475G> A (p.Asp159Asn)single nucleotide variantPathogenicrs137852308GRCh37Chr X, 55047648: 55047648
10ALAS2ALAS2, -206C-Gsingle nucleotide variantPathogenic
11ALAS2NM_000032.4(ALAS2): c.1570C> G (p.His524Asp)single nucleotide variantPathogenicrs137852309GRCh37Chr X, 55039949: 55039949
12ALAS2NM_000032.4(ALAS2): c.595T> C (p.Tyr199His)single nucleotide variantPathogenicrs137852310GRCh37Chr X, 55047528: 55047528
13ALAS2NM_000032.4(ALAS2): c.1354C> T (p.Arg452Cys)single nucleotide variantPathogenicrs137852311GRCh37Chr X, 55041263: 55041263

Expression for genes affiliated with X-Linked Sideroblastic Anemia

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with X-Linked Sideroblastic Anemia

Search GEO for disease gene expression data for X-Linked Sideroblastic Anemia.

Pathways for genes affiliated with X-Linked Sideroblastic Anemia

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51PathCards, 56Reactome, 39NCBI BioSystems Database, 31KEGG, 52PharmGKB
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Pathways related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5HSCB, FXN
2
Show member pathways
TCA cycle39
pyruvate decarboxylation to acetyl CoA39
NAD phosphorylation and dephosphorylation39
TCA Cycle39
conversion of glucose to acetyl CoA and entry into the TCA cycle39
9.4SUCLA2, ACO1
3
Show member pathways
L-serine degradation39
pentose phosphate pathway (oxidative branch)39
formaldehyde oxidation II (glutathione-dependent)39
9.4SUCLA2, ACO1
4
Show member pathways
tetrapyrrole biosynthesis39
heme degradation39
Heme Biosynthesis39
heme biosynthesis39
heme biosynthesis from uroporphyrinogen-III I39
9.3ALAS1, ALAS2
5
Show member pathways
choline degradation I39
glycine biosynthesis III39
serine and glycine biosynthesis39
glycine betaine degradation39
glycine biosynthesis39
9.3ALAS2, ALAS1
6
Show member pathways
7.4ABCB7, SUCLA2, ACO1, ALAS1, ALAS2, FXN

Compounds for genes affiliated with X-Linked Sideroblastic Anemia

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46Novoseek, 25HMDB, 12DrugBank, 30IUPHAR
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Compounds related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

(show all 24)
idCompoundScoreTop Affiliating Genes
1ferric ammonium citrate469.7FXN, ACO1
2protoporphyrin ix46 25 1211.7ABCB7, ALAS2, FXN
3L-2-Amino-3-oxobutanoic acid259.6ALAS2, ALAS1
4deferoxamine46 1210.6ACO1, FXN
5formyl-coa46 2510.6ALAS2, ALAS1
6haem469.5ALAS1, ALAS2
7sulfur469.5FXN, ACO1
8glycine30 25 1211.5ALAS1, ALAS2
9vitamin b6469.4ALAS1, ALAS2
10vitamin-e469.4FXN, ABCB7
11Pyridoxal 5'-phosphate259.3ALAS1, ALAS2
12carbon dioxide46 2510.3ALAS2, ALAS1
13Succinyl-CoA259.2SUCLA2, ALAS1, ALAS2
14Coenzyme A25 1210.2ALAS2, SUCLA2, ALAS1
15iron-sulfur469.1ALAS2, ABCB7, ACO1, FXN
165-aminolevulinic acid46 2510.0ALAS2, ACO1, ALAS1
17zinc46 2510.0ABCB7, ALAS2, FXN, ACO1
18atp46 309.9ALAS2, ACO1, FXN, ABCB7
19glucose468.7FXN, ABCB7, TFE3, ACO1
20leucine468.7ABCB7, ALAS2, ALAS1, TFE3
21cycloheximide468.6ALAS1, ACO1, ALAS2
22heme30 25 1210.4ALAS2, ALAS1, SUCLA2, ABCB7, FXN
23oxygen46 259.2ALAS1, ALAS2, FXN, ABCB7, ACO1
24iron46 258.7FXN, ALAS2, ALAS1, ACO1, HSCB, ABCB7

GO Terms for genes affiliated with X-Linked Sideroblastic Anemia

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17Gene Ontology
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Cellular components related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:0057598.4FXN, ALAS2, ALAS1, SUCLA2
2mitochondrionGO:0057396.6FXN, ABCB7, HSCB, SUCLA2, ACO1, ALAS1

Biological processes related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1tricarboxylic acid cycleGO:0060999.4SUCLA2, ACO1
2protoporphyrinogen IX biosynthetic processGO:0067829.3ALAS2, ALAS1
3porphyrin-containing compound metabolic processGO:0067789.0ALAS1, ALAS2
4heme biosynthetic processGO:0067839.0ALAS2, ALAS1, FXN
5cellular iron ion homeostasisGO:0068798.8FXN, ACO1, ALAS2, ABCB7
6small molecule metabolic processGO:0442818.0ALAS2, FXN, ALAS1, SUCLA2, ABCB7

Molecular functions related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1pyridoxal phosphate bindingGO:0301709.3ALAS2, ALAS1
25-aminolevulinate synthase activityGO:0038709.0ALAS2, ALAS1

Products for genes affiliated with X-Linked Sideroblastic Anemia

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for X-Linked Sideroblastic Anemia

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet