ANH1
MCID: XLN006
MIFTS: 64

X-Linked Sideroblastic Anemia (ANH1) malady

Genetic diseases, Rare diseases, Metabolic diseases, Blood diseases, Bone diseases, Immune diseases categories
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Summaries for X-Linked Sideroblastic Anemia

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NIH Rare Diseases:42 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 based summary: 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 disorders, anaemia and red cell structure/shape anomalies. 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 drugs ferric ammonium citrate and ferric ammonium citrate,green and the compounds ferric ammonium citrate and protoporphyrin ix have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related mouse phenotypes are embryogenesis and mortality/aging.

Genetics Home Reference:21 X-linked sideroblastic anemia is an inherited disorder that prevents developing red blood cells (erythroblasts) from making enough hemoglobin, which is the protein that carries oxygen in the blood. 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.

Description from OMIM:46 300751

Aliases & Classifications for X-Linked Sideroblastic Anemia

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Sources:
8Disease Ontology, 9diseasecard, 65Wikipedia, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet
See all sources

X-Linked Sideroblastic Anemia, Aliases & Descriptions:

Name: X-Linked Sideroblastic Anemia 8 65 42 21 48
Xlsa 8 65 42 21 48
Erythroid 5-Aminolevulinate Synthase Deficiency 42 21 62
Congenital Sideroblastic Anaemia 65 21 62
Anemia Hereditary Sideroblastic 42 20 22
Hereditary Iron-Loading Anemia 65 42 21
Bone Marrow Diseases 65 44 62
Anh1 65 42 21
X-Linked Pyridoxine-Responsive Sideroblastic Anemia 21 62
Anemia, Sex-Linked Hypochromic Sideroblastic 65 21
X Chromosome-Linked Sideroblastic Anemia 42 21
Anemia, Hereditary Sideroblastic 65 21
 
Anemia, Sideroblastic, X-Linked 9 46
Sideroblastic Anemia X-Linked 42 20
Erythroid 5-Aminolaevulinate Synthetase Deficiency 62
Erythroid 5-Aminolevulinate Synthetase Deficiency 65
Anemia Sex-Linked Hypochromic Sideroblastic 42
X Chromosome-Linked Sideroblastic Anaemia 62
Congenital Sideroblastic Anemia 42
Anemia Congenital Sideroblastic 44
Hereditary Sideroblastic Anemia 62
Bone Marrow Disease 10
Hypochromic Anaemia 62
Hypochromic Anemia 65


Classifications:



Characteristics (Orphanet epidemiological data):

48
x-linked sideroblastic anemia:
Inheritance: X-linked recessive; Age of onset: Variable


External Ids:

Disease Ontology8 DOID:0060063
OMIM46 300751
MESH via Orphanet35 C536761
ICD10 via Orphanet26 D64.0

Related Diseases for X-Linked Sideroblastic Anemia

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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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Symptoms by clinical synopsis from OMIM:

300751

Clinical features from OMIM:

300751

Symptoms:

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

HPO human phenotypes related to X-Linked Sideroblastic Anemia:

(show all 11)
id Description Frequency HPO Source Accession
1 anemia hallmark (90%) HP:0001903
2 abnormality of the cardiovascular system occasional (7.5%) HP:0001626
3 abnormality of the spleen occasional (7.5%) HP:0001743
4 respiratory insufficiency occasional (7.5%) HP:0002093
5 type ii diabetes mellitus occasional (7.5%) HP:0005978
6 irregular hyperpigmentation occasional (7.5%) HP:0007400
7 x-linked recessive inheritance HP:0001419
8 sideroblastic anemia HP:0001924
9 macrocytic anemia HP:0001972
10 variable expressivity HP:0003828
11 hypochromic microcytic anemia HP:0004840

Drugs & Therapeutics for X-Linked Sideroblastic Anemia

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Drug clinical trials:

Search ClinicalTrials for X-Linked Sideroblastic Anemia

Search NIH Clinical Center for X-Linked Sideroblastic Anemia

Inferred drug relations via UMLS62/NDF-RT40:

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Genetic Tests for X-Linked Sideroblastic Anemia

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Genetic tests related to X-Linked Sideroblastic Anemia:

id Genetic test Affiliating Genes
1 X-Linked Sideroblastic Anemia20 ALAS2
2 Hereditary Sideroblastic Anemia20 22 YARS2

Anatomical Context for X-Linked Sideroblastic Anemia

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

32
Bone, Bone marrow, Spleen, Liver, Skin, Heart, Lung

Animal Models for X-Linked Sideroblastic Anemia or affiliated genes

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MGI Mouse Phenotypes related to X-Linked Sideroblastic Anemia:

36
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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Articles related to X-Linked Sideroblastic Anemia:

(show all 34)
idTitleAuthorsYear
1
A novel hemizygous I418S mutation in the ALAS2 gene in a young Korean man with X-linked sideroblastic anemia. (24624355)
2014
2
X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. (24166784)
2013
3
X-linked sideroblastic anemia and ataxia: A new family with identification of a fourth ABCB7 gene mutation. (22398176)
2012
4
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
5
New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine. (21252495)
2011
6
Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. (17192398)
2007
7
X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. (16735131)
2006
8
Onset of X-linked sideroblastic anemia in the fourth decade. (15477213)
2004
9
Construction of recombinant vector expressing ALAS2 gene in X-linked sideroblastic anemia]. (15498136)
2004
10
Iron overload due to X-linked sideroblastic anemia in an African American man. (15047047)
2004
11
A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. (12663458)
2003
12
Late-onset X-linked sideroblastic anemia following hemodialysis. (12531813)
2003
13
Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. (12393718)
2002
14
A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia. (12031592)
2002
15
X chromosome inactivation ratios in female carriers of X-linked sideroblastic anemia. (11405213)
2001
16
A novel mutation of the ALAS2 gene in a family with X-linked sideroblastic anemia]. (11877024)
2000
17
Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron- sulfur protein maturation. (11050011)
2000
18
Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. (11110715)
2000
19
Animal models for X-linked sideroblastic anemia. (11039663)
2000
20
X-linked sideroblastic anemia]. (10483144)
1999
21
Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). (10196363)
1999
22
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
23
Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. (9621516)
1998
24
Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene. (9226183)
1997
25
A new mutation of the ALAS2 gene in a large family with X-linked sideroblastic anemia. (7705839)
1995
26
Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia. (7592563)
1995
27
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
28
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
29
X-Linked Sideroblastic Anemia and Ataxia (20301496)
1993
30
Erythroid 5-aminolevulinate synthase and X-linked sideroblastic anemia. (8089650)
1993
31
Enzymatic defect in 'X-linked' sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. (1570328)
1992
32
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
33
X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13. (1671320)
1991
34
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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UniProtKB/Swiss-Prot genetic disease variations for X-Linked Sideroblastic Anemia:

64 (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:

6 (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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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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Pathways related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5FXN, HSCB
2
Show member pathways
TCA cycle37
pyruvate decarboxylation to acetyl CoA37
NAD phosphorylation and dephosphorylation37
TCA Cycle37
conversion of glucose to acetyl CoA and entry into the TCA cycle37
9.4ACO1, SUCLA2
3
Show member pathways
L-serine degradation37
pentose phosphate pathway (oxidative branch)37
formaldehyde oxidation II (glutathione-dependent)37
9.4ACO1, SUCLA2
4
Show member pathways
tetrapyrrole biosynthesis37
heme degradation37
Heme Biosynthesis37
heme biosynthesis37
heme biosynthesis from uroporphyrinogen-III I37
9.3ALAS1, ALAS2
5
Show member pathways
choline degradation I37
glycine biosynthesis III37
serine and glycine biosynthesis37
glycine betaine degradation37
glycine biosynthesis37
9.3ALAS2, ALAS1
6
Show member pathways
7.4FXN, ALAS2, ALAS1, ACO1, SUCLA2, ABCB7

Compounds for genes affiliated with X-Linked Sideroblastic Anemia

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Sources:
44Novoseek, 24HMDB, 11DrugBank, 28IUPHAR
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Compounds related to X-Linked Sideroblastic Anemia according to GeneCards/GeneDecks:

(show all 24)
idCompoundScoreTop Affiliating Genes
1ferric ammonium citrate449.7FXN, ACO1
2protoporphyrin ix44 24 1111.7ABCB7, ALAS2, FXN
3L-2-Amino-3-oxobutanoic acid249.6ALAS2, ALAS1
4deferoxamine44 1110.6FXN, ACO1
5formyl-coa44 2410.6ALAS2, ALAS1
6haem449.5ALAS2, ALAS1
7sulfur449.5ACO1, FXN
8glycine28 24 1111.5ALAS2, ALAS1
9vitamin b6449.4ALAS2, ALAS1
10vitamin-e449.4FXN, ABCB7
11Pyridoxal 5'-phosphate249.3ALAS2, ALAS1
12carbon dioxide44 2410.3ALAS2, ALAS1
13Succinyl-CoA249.2ALAS2, ALAS1, SUCLA2
14Coenzyme A24 1110.2ALAS2, ALAS1, SUCLA2
15iron-sulfur449.1FXN, ALAS2, ACO1, ABCB7
165-aminolevulinic acid44 2410.0ALAS2, ALAS1, ACO1
17zinc44 2410.0ABCB7, ACO1, ALAS2, FXN
18atp44 289.9ABCB7, ACO1, ALAS2, FXN
19glucose448.7ABCB7, TFE3, ACO1, FXN
20leucine448.7ABCB7, TFE3, ALAS1, ALAS2
21cycloheximide448.6ACO1, ALAS1, ALAS2
22heme28 24 1110.4ABCB7, SUCLA2, ALAS1, ALAS2, FXN
23oxygen44 249.2ABCB7, ACO1, ALAS1, ALAS2, FXN
24iron44 248.7ABCB7, HSCB, ACO1, ALAS1, ALAS2, FXN

GO Terms for genes affiliated with X-Linked Sideroblastic Anemia

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

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

Sources for X-Linked Sideroblastic Anemia

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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