An Overview Of Thalassemia And Recent Clinical Research Biology Essay

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Thalassemia is a group of recessive diseases of the red blood cells (RBCs). In these patients there is a marked lowered rate of production of hemoglobin. As a result, the red blood cells are prone to mechanical injury and have significantly shortened life spans. It has been proven that patients with thalassemia, may be somewhat protect from malaria.


Alpha (α) thalassemias

Alpha thalassemias involve the following genes: HBA1 and HBA2 which are recessively inherited(Sengupta). This leads to decreased alpha chain production and excess gamma and beta chains, in newborns and adults respectively. The beta chains have unstable tetramers and as a result add to the abnormal O2 dissociation curves. Two maternal and two paternal loci determine the expression of the alpha globulin. The more loci affected, the more severe the disease.

Damage of all 4 loci results in death of the individual soon after birth. These individuals are born with edema and very low hemoglobin production , if at all.

If 3 loci are damaged, then the patient develops Hemoglobin H disease. Unstable Barts Hb and HbH are observed circulating in the blood. Target cells may also be present with microcytic anemia as well as Heinz bodies on the outside of the blood smear. This is due to the heterozygous alpha thalassemia type one and two.

If only two of the loci are affected, Alpha thalassemia type 1 occurs. With two loci, there is normal RBC production but microcytic anemia may still be observed in the individual. Deletion of 1 of the 2 loci in the chromosomes of African Americans is common. One type of deletion is cis, in which two loci on the same chromosome are deleted and the other kind if trans where there is deletion of genes on the homologous chromosomes number 16.

However, if only 1 of the 4 loci is damaged, the individual is diagnosed with alpha minor thalassemia or type 2. The 3 intact loci direct normal RBC and hemoglobin production. These individuals are only carriers for the alpha thalassemia trait, often with no symptoms.

Beta (β) thalassemias

Cooley's Anemia is primarily caused by a mutation in chromosome 11 of the HBB gene(Gardenghi). It is inherited in a recessive fashion. In this type, there is a decrease in the normal amount of beta chains to be made. This of course leads to an increase in the number of alpha chains present. These alpha chains bind to RBC membranes and damage them. The severity of the disease varies. Every person has two beta globin alleles, one from the father and one from the mother.

If both the alleles have the mutation, Beta thalassemia major or Cooley's anemia ensues. If untreated the patient will die before reaching 20 years old. Blood transfusion is the preferred method of treatment and transfusion-caused iron overload treatment. In some cases, bone marrow transplantation has led to a cure for this disease.

However if only one allele has the mutation, B-thalassemia minor ensues. This is relatively minor anemia with microcytosis. Beta thalassemia minor is asymptomatic in most cases.

Thalassemia intermedia is a condition between the minor and major forms. Broadly there are two main mutations that cause Beta thalassemias:

Nondeletion forms involve 1 base substitution or a deletion or insert upstream of the beta globin gene. Usually mutations occur in the promoter regions before the beta globin genes. Deletion and mutation in genes produce beta thalassemia.

Deletion forms involve the beta globin gene producing different syndromes like hereditary persistence of fetal hemoglobin syndrome and delta thalassemia.

Mutations in the delta chain may prevent any formation of delta chains - delta0 and one that decreases formation is delta+ mutation. People who obtain only 1 delta allele will have decrease A2 hemoglobin but with normal RBC function. Often delta thalassemia masks the diagnosis of the beta trait. In beta, there is an increased production of hemoglobin A2, however if delta thalassemia exists also, it will decrease the value of A2 into the normal range of values.

Thalassemia usually occurs with other hemoglobin related diseases. Thalassemia E is similar in onset to Beta thalassemia major or thalassemia intermedia. Thalassemia S is similar in nature to sickle cell anemia, but there is an enlarged spleen. Thalassemia C causes a severe hemolytic anemia with enlarged spleen.


Diagnosis of thalassemias is usually done with a complete blood test and hemoglobin tests. A CBC gives information about the hemoglobin in the blood and the different cells, like small RBCs in the sample. Thalassemia is characterized by little to none RBCs and a decreased amount of hemoglobin in the blood. Hemoglobin exams help reveal the problems with the alpha or beta chains of the hemoglobin in the blood.

Usually people with severe thalassemia are diagnosed in childhood because severe anemia occurs within the first 2 years. Patients with mild forms are diagnosed after a complete blood count Also being part of a certain race may put an individual at a higher risk for this disease. So naturally they are screened for the exam at an earlier age. Physicians also may test the iron content to differentiate between iron deficiency, occurs when there is not enough iron to produce functional hemoglobin, or thalassemia. Thalassemia can also be seen through genetic studies involving the family medical history as well as looking at blood test results of family members. Prenatal testing is quite common and involves taking amniotic fluid, fluid surrounding the fetus, from the placenta.


Thalassemia usually exists with folic acid and iron deficiencies. Patients with thalassemia may also have iron overload due to the inherited defects in the regulation of iron. Thalassemia major patients obtain periodic blood transfusions that usually lead to an overload in iron in the body. Thalassemia intermedia individuals vary in the treatment they need. All individuals with thalassemia are more prone than normal to splenomegaly, and production of gallstones. Another option is iron chelation, which is used to prevent the iron overload in the body. The most commonly used chelators are defroxamine, the more preferred one, and deferiprone. However patients complain because taking intravenous chelation treatments become painful and are usually not voluntarily done. There has recently been released an oral chelator, Exjade, which was recently approved but its cost was $12,000(Agarwal). If left untreated, thalassemia major leads to heart failure, which leads to death, prenatal screening can greatly reduce the chances of this happening.

Recently, stem cell transplantation has been showed to be very effective for sufferers of thalassemia major. (S. Agrawal) successful treatment eliminates the need for transfusions.Studies have shown that thalassemia minor usually exists with other diseases such as asthma and even bipolar.


Alpha and beta thalassemias are usually autosomal recessively, but this is not always true. In rare instances there has been reported dominantly inherited alpha and beta thalassemia. (Faustino). It was reported that the first was in an Irish family who had two deletions for 11 and 4 base pairs in exon 3, interrupted by insertion of the 5 base pairs in the beta globin gene. However, for the autosomally recessive patients, both patients must be carriers for the child to affected. Genetic counseling is essential in the prevention of this disease.

There are over 60-80 million beta thalassemia carriers for this trait alone. The real number of people with thalassemia major is unknown. In countries such as Iran, Pakistan and India, there has been a great increase in the number of people affected by thalassemia due to the lack of genetic counseling and screening. To date, there are over 1,000 known cases of thalassemia major in the United States, and an unknown number of carriers. Birth screening and genetic counseling can greatly reduce the prevalence of this disease.


Some people with the carrier gene may offer some protection against malaria, and its is common in Italian and Greek people, and some African and Indian regions (Wambua). This makes the blood cells more likely to be wanted by the less lethal species plasmodium vivax, while also making the host red blood cell's environment uninhabitable for the merozoites of the lethal stain falciparum. Some people may have protection against severe anemia and others have been reported to have some protection against coronary heart disease.

Case Report

A 19-year-old boy is screened for beta thalassemia minor. It is found that the variant hemoglobin migrated in the HbS position on the electrophoresis gel at basic pH. The patient did not display any symptoms and did not have any prior medical or familial history of the illness. A cell counter was used to obtain cell counts and there were thalassemia indices present, however when a solubility test was done, sickly was not present. Hb electrophoresis was done at 8.4 pH to test for the beta thalassemia trait, however an alpha chain variant in the heterozygous state was found (Desai).

It was a confirmed case of Hb Q-India. When the family was studied it showed the same mutation in the mother and father and sister. Hb Q mutations occur in structural mutations. Hb-Thailand, HbQ-India and HbQ-Iran are the three known variants of the alpha globin chain. Wheather HbQ occurs with beta thalassemia or not, it is silent. Elecrophoresis, and chromatography were used to find this variant.

The gel shows Hb mobility in the Patient, mother, father, sister and a control of the sickling trait. When a liquid chromatography was done, it was confirmed there was a Hb Q-India with the B thalassemia trait. The family had a similar gel(Desai).