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| | MeshID = D017086 | | | MeshID = D017086 |
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| {{SI}} | | {{Beta-thalassemia}} |
| {{CMG}} | | {{CMG}}; {{AE}} {{MHP}} |
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| {{SK}} Cooley anaemia; ߺ thalassemia; thalassemia major; | | {{SK}} Cooley anaemia; ߺ thalassemia; thalassemia major; |
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| ==Overview== | | ==[[Beta-thalassemia overview|Overview]]== |
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| '''Beta-thalassemia''' (β-thalassemia) is a form of [[thalassemia]] due to mutations in the [[HBB]] gene on [[chromosome 11]] <ref>{{OMIM|141900}}</ref>, inherited in an [[autosomal recessive]] fashion.
| | ==[[Beta-thalassemia historical perspective|Historical Perspective]]== |
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| The severity of the disease depends on the nature of the mutation.
| | ==[[Beta-thalassemia classification|Classification]]== |
| * Mutations are characterized as (β<sup>o</sup>) if they prevent any formation of β chains.
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| * Mutations are characterized as (β<sup>+</sup>) if they allow some β chain formation to occur.
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| * Alleles without a mutation that reduces function is characterized as (β). (Note that the "+" in β<sup>+</sup> is relative to β<sup>o</sup>, not β.)
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| In either case there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the [[red blood cell]] membranes, producing membrane damage, and at high concentrations they form toxic aggregates.
| | ==[[Beta-thalassemia pathophysiology|Pathophysiology]]== |
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| ==Classification== | | ==[[Beta-thalassemia differential diagnosis|Differentiating Beta-thalassemia from other Diseases]]== |
| Any given individual has two β globin alleles:
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| {| class="wikitable"
| | ==[[Beta-thalassemia epidemiology and demographics|Epidemiology and Demographics]]== |
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| ! Name
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| ! Description
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| ! Alleles
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| | '''β thalassemia minor''' (sometimes called '''β thalassemia trait''')
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| | If only ''one'' β globin allele bears a mutation. This is a mild [[microcytic anemia]]. Detection usually involves measuring the [[mean corpuscular volume]] (size of red blood cells) and noticing a slightly decreased mean volume than normal. The patient will have an increased fraction of [[Hemoglobin A2]] (>2.5%) and a decreased fraction of [[Hemoglobin A]] (<97.5%).
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| | β<sup>+</sup>/β or β<sup>o</sup>/β
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| |-
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| | '''β thalassemia major''' or '''Cooley's anemia'''
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| | If ''both'' alleles have thalassemia mutations. This is a severe microcytic, hypochromic [[anemia]]. Untreated, this progresses to death before age twenty. Treatment consists of periodic [[blood transfusion]]; splenectomy if splenomegaly is present, and treatment of transfusion-caused iron overload. Cure is possible by [[bone marrow transplantation]]. | |
| | β<sup>+</sup>/β<sup>+</sup> or β<sup>o</sup>/β<sup>o</sup>
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| | '''Thalassemia intermedia'''
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| | A condition intermediate between the major and minor forms. Affected individuals can often manage a normal life but may need occasional transfusions e.g. at times of illness or pregnancy, depending on the severity of their anemia.
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| | β<sup>+</sup>/β<sup>+</sup> or β<sup>o</sup>/β
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| |}
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| Note that β<sup>+</sup>/β<sup>+</sup> can be associated with β thalassemia minor or β thalassemia intermedia.
| | ==[[Beta-thalassemia risk factors|Risk Factors]]== |
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| ==Pathophysiology== | | ==[[Beta-thalassemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| The genetic mutations present in β thalassemias are very diverse, and a number of different mutations can cause reduced or absent β globin synthesis. Two major groups of mutations can be distinguished:
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| * '''Nondeletion forms''': These defects generally involve a single base substitution or small deletion or inserts near or upstream of the β globin gene. Most commonly, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease.
| | ==Diagnosis== |
| * '''Deletion forms''': Deletions of different sizes involving the β globin gene produce different syndromes such as (β<sup>o</sup>) or hereditary persistence of fetal hemoglobin syndromes.
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| ==Treatment and complications==
| | [[Beta-thalassemia history and symptoms|History and Symptoms ]] | [[ Beta-thalassemia physical examination|Physical Examination]] | [[Beta-thalassemia laboratory findings|Laboratory Findings]] | [[Beta-thalassemia x ray|X Ray]] | [[Beta-thalassemia CT|CT]] | [[Beta-thalassemia MRI|MRI]] | [[Beta-thalassemia ultrasound|Ultrasound]] | [[Beta-thalassemia other imaging findings|Other Imaging Findings]] | [[Beta-thalassemia other diagnostic studies|Other Diagnostic Studies]] |
| Anyone with thalassemia should consult a properly qualified [[hematologist]].
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| Thalassemias may co-exist with other deficiencies such as [[folic acid]] (or folate, a B-complex vitamin) and [[iron deficiency]] (only in Thalassemia Minor).
| | ==Treatment== |
| | [[Beta-thalassemia medical therapy|Medical Therapy]] | [[Beta-thalassemia surgery |Surgery]] | [[Beta-thalassemia primary prevention|Primary Prevention]] | [[Beta-thalassemia secondary prevention|Secondary Prevention]] | [[Beta-thalassemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Beta-thalassemia future or investigational therapies|Future or Investigational Therapies]] |
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| ===Thalassemia Major and Intermedia=== | | ==Case Studies== |
| Thalassemia Major patients receive frequent [[blood transfusions]] that lead to [[iron overload]]. Iron [[chelation treatment]] is necessary to prevent iron overload damage to the internal organs in patients with Thalassemia Major. Because of recent advances in iron chelation treatments, patients with Thalassemia Major can live long lives if they have access to proper treatment. Popular chelators include [[deferoxamine]] and [[deferiprone]]. Of the two, deferoxamine is preferred; it is more effective and is associated with fewer [[Adverse effect (medicine)|side-effects]].<ref>{{cite journal | author=Maggio A, D'Amico G, ''et al.''
| | [[Beta-thalassemia case study one|Case #1]] |
| | title=Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial
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| | journal=Blood Cells Mol Dis | |
| | year=2002
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| | volume=28
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| | issue=2
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| | pages=196–208
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| | pmid=12064916 | doi=10.1006/bcmd.2002.0510
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| }}</ref>
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| The most common complaint by patients receiving deferoxamine is that it is difficult to comply with the subcutaneous chelation treatments because they are painful and inconvenient. The oral chelator [[deferasirox]] (marketed as Exjade by Novartis) was approved for use in 2005 in some countries. It offers some hope with compliance but is very expensive (~US$100 per day) and has been associated with deaths from toxicity.
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| Untreated thalassemia Major eventually leads to death usually by [[heart failure]], therefore birth screening is very important.
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| [[Bone marrow transplant]]ation is the only cure for thalassemia, and is indicated for patients with severe thalassemia major. Transplantation can eliminate a patient's dependence on transfusions.
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| All Thalassemia patients are susceptible to health complications that involve the [[spleen]] (which is often enlarged and frequently removed) and gall stones. These complications are mostly prevalent to thalassemia Major and Intermedia patients.
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| Thalassemia Intermedia patients vary a lot in their treatment needs depending on the severity of their anemia.
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| ===Thalassemia Minor===
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| Contrary to popular belief, Thalassemia Minor patients should not avoid iron-rich foods by default. A serum [[ferritin]] test can determine what their iron levels are and guide them to further treatment if necessary. Thalassemia Minor, although not life threatening on its own, can affect quality of life due to the effects of a mild to moderate [[anemia]]. Studies have shown that Thalassemia Minor often coexists with other diseases such as [[asthma]]<ref>{{cite journal | author=Palma-Carlos AG, Palma-Carlos ML, Costa AC
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| | title="Minor" hemoglobinopathies: a risk factor for asthma
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| | journal=Allerg Immunol (Paris)
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| | year=2005 |pmid=15984316
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| | volume=3
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| | issue=5
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| | pages=177–82 }}</ref>, and [[mood disorders]]<ref>{{cite journal | author=Brodie BB
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| | title=Heterozygous β-thalassaemia as a susceptibility factor in mood disorders: excessive prevalence in bipolar patients
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| | journal=Clin Pract Epidemiol Mental Health
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| | year=2005
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| | volume=1
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| | pages=6 |pmid=15967056 |pmc=1156923 |url=http://www.cpementalhealth.com/content/1/1/6
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| | doi=10.1186/1745-0179-1-6 }}</ref>.
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| ==References==
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| {{reflist|2}}
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| {{Myeloid hematologic disease}} | | {{Myeloid hematologic disease}} |
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| [[Category:Genetic disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Blood disorders]] | | [[Category:Blood disorders]] |
| | | [[Category:Disease]] |
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