Thalassemia

Introduction Thalassemia is a form of genetically inherited autosomal recessive blood disorders. This, as the Chinese name implies, originated in the regions of the Mediterranean. When a person acquires thalassemia, the red blood cells are weakened and destroyed. This is due to the cause of variant or missing genes that highly affects or influences the way the body makes hemoglobin. Hemoglobin is a protein, found in the red blood cells, that is in charge of carrying oxygen. When people acquire thalassemia, they make less hemoglobin and the count of circulating red blood cells is also lower than normal. This can also result in mild or severe anemia. However this is different from the normal common acquired anemia. Thalassemia is usually present as a microcytic anemia, different from the deficiency anemia. There are many common symptoms that occur in people who are inherited with thalassemia. Some of the significant complications include iron overload, bone deformities, and also cardiovascular illnesses. On the other hand, however, this genetically inherited disease of the red blood cells somehow provides a certain degree of protection against another disease known as malaria. Malaria was a prevalent disease in the regions where this disorder was common. This selective survival advantage on carriers, heterozygous advantage, might be responsible for some mutations in populations through years to come. This disease is not to be confused with another genetic disorder that affects the hemoglobin, sickle-cell disease. Major Symptoms/Complications 1. Iron overload: People who have the thalassemia disorder commonly experience iron overload. This is usually cause by two reasons: from the disease itself, or through frequent blood transfusions. The effect of having too much iron accumulated in the body results in the damage of the heart, liver and the endocrine system, which is the system of glands in charge of producing hormones to regulate many processes throughout the body. These damages are usually identified by excessive deposits of iron. Almost all patients would accumulate fatal levels of iron in their body if they are not properly treated with iron chelation therapy. 2. Enlarged spleen: The bodys spleen is in charge of aiding in the battle against infections and filtering unwanted materials in the body, including old, or damaged cells. However, because thalassemia is characterized with the accompany of large numbers of red blood cells being destroyed, the task of removing all these damaged, unwanted red blood cells results in the enlargement of the spleen. As a result, if the spleen enlarges severely, it may be removed.

3. Slow growth rate: Anemia caused by this genetic disorder may slow down the growth of children. Thus, even puberty might be delayed in many children with this disorder. Pathophysiology Normally, the composition of the majority of adult hemoglobin entails four protein chains; two alpha and two beta, being arranged in a heterotetramer. Since thats the case, when a patient is diagnosed with thalassemia, they either have defects in the alpha globin chain or the beta globin chain. This defect of the globin chains causes the production of abnormal red blood cells. This is also a major distinction between the thalassemia genetic disorder and the sickle-cell disease. In sickle-cell disease, the mutation is only specific to only the beta globin. Since the defects occur on either alpha globin chains or beta globin chains, the thalassemia is also classified accordingly to which chain of the hemoglobin molecule is affected. In alpha-thalassemia, production of the alpha globin chain is affected, whilst in the beta thalassemia, the production of the beta globin chain is affected. The beta globin chains are encoded by a single gene on chromosome 11 whilst the alpha globin chains are encoded by two closely linked genes on chromosome 16. This is a major distinction between alpha thalassemia and beta thalassemia. Thus, since there are two copies or each chromosomes in a normal person, it counts down to the fact that there are two loci encoding the beta chain and four loci encoding the alpha chain. In Africans or Asians, the deletion of one of the alpha loci is of a high prevalence, which makes them more likely to develop alpha thalassemia. However, beta thalassemia is common in Greeks and Italians, and in Africans as well. Alpha Thalassemia The genes involved in alpha thalassemia are HBA1 and HBA2. These genes are genetically inherited in the Mendelian recessive fashion. Since there are two loci, that makes four alleles, also being connected to the deletion of the 16p chromosome. This type of thalassemia results in a decreased alpha globin production, and thus, fewer alpha globin chains are produced. On the other hand, beta chains will be produced in excess in adults and gamma chains will be produced in excess in new born babies. The excess of beta chains will form unstable tetramers causing abnormal oxygen dissociation curves.

Beta Thalassemia This type of thalassemia is caused by a mutation in the HBB gene located on chromosome 11, which is also genetically inherited in an autosomal-recessive fashion. However, in beta thalassemia, the severity of the disease depends on the nature of the mutation. The mutations are classified as beta thalassemia major if they prevent any formation of beta chains. They are also classified as beta positive or beta thalassemia intermedia if they allow some beta chain formation to occur. However, in both cases, there is still relatively excessive amounts of alpha chains, but they do not form tetramers. They simply bind to the membranes of the red blood cell, causing damage to the membrane, and form toxic aggregates at high concentrations. Delta thalassemia There is another type of hemoglobin in adults that is made of alpha chains and delta chains. Such hemoglobin are only about three percent in the human body. If a there is a mutation in this gene, it also affects the formation of delta chains. Medications Iron overload that is caused by multiple blood transfusions can be treated with chelation therapy with medications such as deferoxamine, which is only effective via daily injections, making its long term use a little difficult but inexpensive, deferiprone and deferasirox, which are both oral medications. These treatments have proved to improve life expectancy of patients diagnosed with thalassemia major. Bone Marrow Transplant Bone marrow transplants are a possibility of curing people who a lucky enough to get a HLA-matched donor. Today, the success rates of this procedure have improved to about 80-90%. The percentage of patients dying after the procedure is 3%. If a person is not able to get a HLA-matched donor, there is another method they can go through, which is the haploidentical mother to child, whereby, the mother is the donor. However, the result of this procedure show better with very young patients than with older patients.