Beta-thalassemia

Overview
Beta-thalassemia (β-thalassemia) is a form of thalassemia due to mutations in the HBB gene on chromosome 11, inherited in an autosomal recessive fashion.

The severity of the disease depends on the nature of the mutation.
 * Mutations are characterized as (βo) if they prevent any formation of β chains.
 * Mutations are characterized as (β+) if they allow some β chain formation to occur.
 * Alleles without a mutation that reduces function is characterized as (β). (Note that the "+" in β+ is relative to βo, not β.)

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.

Types
Any given individual has two β globin alleles:

Note that β+/β+ can be associated with β thalassemia minor or β thalassemia intermedia.

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:


 * 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.
 * Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (βo) or hereditary persistence of fetal hemoglobin syndromes.

Treatment and complications
Anyone with thalassemia should consult a properly qualified hematologist.

Thalassemias may co-exist with other deficiencies such as folic acid (or folate, a B-complex vitamin) and iron deficiency (only in Thalassemia Minor).

Thalassemia Major and Intermedia
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 side-effects.

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.

Untreated thalassemia Major eventually leads to death usually by heart failure, therefore birth screening is very important.

Bone marrow transplantation is the only cure for thalassemia, and is indicated for patients with severe thalassemia major. Transplantation can eliminate a patient's dependence on transfusions.

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.

Thalassemia Intermedia patients vary a lot in their treatment needs depending on the severity of their anemia.

Thalassemia Minor
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, and mood disorders.