These treatments have resulted in longer life expectancy for those with thalassemia major.Deferoxamine is only effective as a daily injection, complicating its long-term use. However, it is inexpensive and safe. Adverse effects include primary skin reactions around the injection site and hearing loss.Deferasirox and deferiprone are both oral medications, whose common side effects include nausea, vomiting and diarrhea. Deferasirox is not effective for all patients and may not be suitable for those with significant cardiac issues related to iron overload, while deferiprone appears to be the most effective agent when the heart is involved. Furthermore, the cost of deferasirox is also significant.There is no evidence from randomized controlled trial to support zinc supplementation for those with thalassemia. Bone-marrow transplantation
Bone-marrow transplantation may offer the possibility of a cure in young people who have an HLA-matched donor. Success rates have reached the 80–90% range. Mortality from the procedure is about 3%. There are no randomized controlled trials that have tested the safety and efficacy of non-identical donor bone-marrow transplantation in persons with β- thalassemia who are dependent on blood transfusion.Graft-versus-host diseases (GvHD) are one relevant side effect of bone-marrow transplantation. Further research is necessary to evaluate whether mesenchymal stromal cells can be used as prophylaxis or treatment for GvHD.If the patient does not have an HLA-matched compatible donor, bone-marrow transplantation from haploidentical mother to child (mismatched donor) may be attempted. In a study of 31 people, the thalassemia-free survival rate was 70%, rejection 23% and mortality 7%. The most positive results tend to occur with very young people.
Cause
Both α- and β-thalassemias are often inherited in an autosomal recessive manner. Cases of dominantly inherited α- and β-thalassemias have been reported, the first of which was in an Irish family with two deletions of 4 and 11 bp in exon 3 interrupted by an insertion of 5 bp in the β-globin gene. For the autosomal recessive forms of the disease, both parents must be carriers for a child to be affected. If both parents carry a hemoglobinopathy trait, the risk is 25% for each pregnancy for an affected child.The genes involved in thalassemia control the production of healthy hemoglobin. Hemoglobin binds oxygen in the lungs and releases it when the red cells reach peripheral tissues, such as the liver. The binding and release of oxygen by hemoglobin are essential for survival. Evolution
Having a single genetic variant for thalassemia may protect against malaria and thus can be an advantage.People diagnosed with heterozygous (carrier) β-thalassemia have some protection against coronary heart disease. Pathophysiology
Normally, the majority of adult hemoglobin (HbA) is composed of four protein chains, two α and two β-globin chains arranged into a heterotetramer. In thalassemia, patients have defects in either the α or β-globin chain, causing production of abnormal red blood cells.The thalassemias are classified according to which chain of the hemoglobin molecule is affected.