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X-linked sideroblastic anemia

Reviewed October 2006

What is X-linked sideroblastic anemia?

X-linked sideroblastic anemia is an inherited disorder that prevents red blood cells (erythrocytes) from making sufficient hemoglobin, the iron-containing protein that carries oxygen in the blood. In X-linked sideroblastic anemia, red blood cells cannot use iron efficiently to make hemoglobin. As a result, the body tries to compensate by absorbing more iron from the diet. Iron that is not incorporated into hemoglobin builds up in other tissues and organs in the body, where it can cause damage.

The signs and symptoms of this disorder range from mild to severe and usually begin by the age of 30. The characteristic features of this disorder include pale skin, fatigue, dizziness, and an enlarged spleen and liver. Heart disease, liver damage, and kidney failure are severe medical problems that can result from the buildup of iron in these organs.

How common is X-linked sideroblastic anemia?

This form of anemia is very rare; several hundred cases have been reported worldwide.

What genes are related to X-linked sideroblastic anemia?

Mutations in the ALAS2 gene cause X-linked sideroblastic anemia.

Mutations in the HFE gene modify the course of X-linked sideroblastic anemia.

The ALAS2 gene provides instructions for making an enzyme called ALA-synthase, which is critical in the chemical process that leads to heme production. Heme is part of the hemoglobin protein and is vital for supplying oxygen to the entire body. When the ALAS2 gene is mutated, heme cannot be produced normally. As a result, not enough hemoglobin is made, allowing iron to build up and damage the body's tissues.

People who inherit mutations in the HFE gene, along with a mutation in the ALAS2 gene, may experience particularly severe signs and symptoms of X-linked sideroblastic anemia. Mutations in the HFE gene can also lead to increased absorption of iron from the diet and result in hemochromatosis, which is another type of iron overload disorder. A more serious iron overload can occur from the combined effect of these two mutations on iron absorption.

How do people inherit X-linked sideroblastic anemia?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. Some females with one altered copy of the ALAS2 gene may exhibit some signs and symptoms related to this condition. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about treatment for X-linked sideroblastic anemia?

You may find information on treatment or management of X-linked sideroblastic anemia or some of its symptoms in the links below, particularly the links for MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about X-linked sideroblastic anemia?

You may find the following resources about X-linked sideroblastic anemia helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Anemia (http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm)
    • Health Topic: Anemia (http://www.nlm.nih.gov/medlineplus/anemia.html)
    • Health Topic: Blood and Blood Disorders (http://www.nlm.nih.gov/medlineplus/bloodandblooddisorders.html)
  • Educational resources - Information pages
    • Ask the Geneticist: Inheritance of sideroblastic anemia (http://www.genetics.emory.edu/ask/question.php?question_id=4635)
    • Great Ormond Street Hospital for Children NHS Trust (UK) (http://www.gosh.nhs.uk/factsheets/families/F010082/index.html#sideroblast)
    • Information Center for Sickle Cell and Thalassemic Disorders, Harvard University (http://sickle.bwh.harvard.edu/sideroblastic.html)
    • Iron Disorders Institute (http://www.irondisorders.org/Disorders/Sideroblastic.asp)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,284/)
    • Mount Sinai School of Medicine (http://www.mssm.edu/genetics/xlsa.shtml)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1047)
  • Patient support - For patients and families
    National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Anemias%2C%20Sideroblastic)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22X-linked+sideroblastic+anemia%22+OR+%22Anemia%2C+Sideroblastic%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Anemia,+Sideroblastic[MAJR])+AND+((x-linked+sideroblastic+anemia[TIAB])+OR+(x-linked[TIAB]+AND+sideroblastic+anemia[TIAB])+OR+(XLSA[TIAB]))+NOT+(ataxia[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=3600+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Disorders of Heme Biosynthesis: X-Linked Sideroblastic Anemia and the Porphyrias (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=124)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300751)

What other names do people use for X-linked sideroblastic anemia?

  • Anemia, hereditary sideroblastic
  • Anemia, sex-linked hypochromic sideroblastic
  • ANH1
  • Congenital sideroblastic anaemia
  • Erythroid 5-aminolevulinate synthetase deficiency
  • Hereditary iron-loading anemia
  • Hypochromic anemia
  • X chromosome-linked sideroblastic anemia
  • X-linked pyridoxine-responsive sideroblastic anemia
  • XLSA

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked sideroblastic anemia?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding X-linked sideroblastic anemia?

anemia ; cell ; chromosome ; congenital ; deficiency ; enlarged spleen ; enzyme ; erythrocyte ; gene ; heme ; hemoglobin ; hypochromic ; inheritance ; iron ; kidney ; mutation ; oxygen ; protein ; recessive ; red blood cell ; sex chromosomes ; sign ; symptom ; synthetases ; tissue ; trait ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Aivado M, Gattermann N, Rong A, Giagounidis AA, Prall WC, Czibere A, Hildebrandt B, Haas R, Bottomley SS. X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells Mol Dis. 2006 Jul-Aug;37(1):40-5. Epub 2006 Jun 2. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16735131)
  • Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys Acta. 2006 Jul;1763(7):723-36. Epub 2006 Jun 3. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16839620)
  • Bottomley SS, May BK, Cox TC, Cotter PD, Bishop DF. Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia. J Bioenerg Biomembr. 1995 Apr;27(2):161-8. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=7592563)
  • Cazzola M, May A, Bergamaschi G, Cerani P, Rosti V, Bishop DF. Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. Blood. 2000 Dec 15;96(13):4363-5. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11110715)
  • Cotter PD, May A, Li L, Al-Sabah AI, Fitzsimons EJ, Cazzola M, Bishop DF. 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. Blood. 1999 Mar 1;93(5):1757-69. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10029606)
  • Fleming MD. The genetics of inherited sideroblastic anemias. Semin Hematol. 2002 Oct;39(4):270-81. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12382202)
  • May A, Bishop DF. The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia. Haematologica. 1998 Jan;83(1):56-70. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=9542324)
  • Nakajima O, Takahashi S, Harigae H, Furuyama K, Hayashi N, Sassa S, Yamamoto M. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J. 1999 Nov 15;18(22):6282-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10562540)
  • Roy CN, Andrews NC. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum Mol Genet. 2001 Oct 1;10(20):2181-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11673399)
  • Sadlon TJ, Dell'Oso T, Surinya KH, May BK. Regulation of erythroid 5-aminolevulinate synthase expression during erythropoiesis. Int J Biochem Cell Biol. 1999 Oct;31(10):1153-67. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10582344)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2006
Published: January 23, 2009