DNA contains both the instructions (genes) for stringing amino acids together into proteins, as well as stretches of DNA that play important roles in regulating produced protein levels.In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the intronic and exonic portions of the DNA template. Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoblogins normal alpha and beta subunits each have an iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits. Thalassemias typically affect only the mRNAs for production of the beta chains (hence the name). Since the mutation may be a change in only a single base (single-nucleotide polymorphism), on-going efforts seek gene therapies to make that single correction. Risk factors
Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on family history, if a persons parents or grandparents had beta thalassemia major or intermedia, there is a 75% (3 out of 4) probability (see inheritance chart at top of page) of the mutated gene being inherited by an offspring. Even if a child does not have beta thalassemia major or intermedia, they can still be a carrier, possibly resulting in future generations of their offspring having beta thalassemia.Another risk factor is ancestry.
The three iron chelators; subcutaneous deferoxamine, oral deferiprone and oral deferasirox can be used as monotherapy or in combination, they have all been shown to decrease serum/systemic iron levels, hepatic and cardiac iron levels as well as decreasing the risk of cardiac arrhythmia, heart failure and death. Hepatic and myocardial MRI is also used to quantify the iron deposition in target organs, especially the heart and liver, to guide therapy.Scientists at Weill Cornell Medical College have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production.On June 10, 2022, a U.S. federal advisory panel recommended that the FDA approve a gene therapy treatment for use with beta thalassemia. Surgical
Patients with thalassemia major are more inclined to have a splenectomy. The use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Splenectomy is also associated with increased risk of infections and increased morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells. Patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. The different surgical techniques are the open and laparoscopic method.