All about Thalassemia (A Blood Borne Disease)

Background

Thalassemia is an autosomal recessive blood disorder. In thalassemia, the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. (Hemoglobin is made up of 4 polypeptide subunit: 2 alpha globin chain + 2 beta globin chain). The reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, and hence causing anemia.

There is two kind of thalassemia which is alpha thalassemia, whereby the alpha globin chain is affected, and beta thalassemia, whereby the beta globin chain is affect.

Thalassemia (alpha and beta) is also classified as two form: thalassemia major and thalassemia minor

Thalassemia major occurs when defective genes are inherited from both parents while thalassemia minor occurs if you receive the defective gene from only one parent. Persons with this form of the disorder are carriers of the disease and usually have very mild or do not have any symptoms at all.

 Four genes, two genes (HBA1 and HBA2) from each parents, are required to form the alpha globin chain. The severity to alpha thalassemia depends on how many genes are missing or mutated. When only one of the genes are affected, it has a minimal effect on the carrier.
There would be no clinical symptoms as 3 alpha globin genes are enough to allow normal hemoglobin production. Those who has only one alpha gene affected are called the “silent carriers”.

An Alpha thalassemia trait occurs when two of the 4 genes are affected. Although 2 genes are enough to allow nearly normal erythropoiesis, affected individuals may still have mild microcytic hypochromic anemia (red blood cells are paler and smaller than normal). Individuals who are develop this anemia may sometime experience lack of energy, shortness of breath, dyspepsia, headaches, a capricious or scanty appetite and amenorrhea.

Severe alpha thalassemia occurs when more than 2 gene are affected. When 3 genes are affected, one would develop a condition call Hemoglobin H disease where by the hemoglobin (Hemoglobin Barts and Hemoglobin H) present in the blood are unstable. These unstable hemoglobin has a high affinity for oxygen than in normal hemoglobin and hence causing poor oxygen delivery to the tissues. Severe alpha thalassemia occurs when 4 genes are affected, this results in hydrops fetalis whereby they cannot live once outside the uterus and are not able to survive gestation.

Alpha thalassemia occur most commonly in individuals from the southeast Asia (SEA), the Middle East, China, and in those of African descent.

TreatmentAffected individuals with mild forms of alpha thalassemia (with only one or two genes affected) may not require specific treatment however there may be a need for management of low hemoglobin levels via supplements like iron or folic acid. Patients with more severe anemia may require lifelong regular blood transfusion therapy. Children with alpha thalassemia may require bone marrow transplant in order to treat the disease.

HBB gene is important for the making of beta-globin, a subunit of hemoglobin. Studies have shown that there is more than 250 mutation in HBB gene that cause beta thalassemia. Most mutation involve a change in single DNA nucleotide within or near the HBB gene, while other mutation involves insert or deletion of a small number of nucleotide in HBB gene.  

People with HBB mutations can be diagnosed with thalassemia major and thalassemia intermediate.

In Beta Thalassemia minor, only one out of the two beta globin genes is mutated. This is insufficient to cause a problem in the normal functioning of hemoglobin. Individual with Beta Thalassemia minor will only carry the genetic trait and will not experience any health issues.

Beta-Thalassemia Major (also known as Cooley’s anemia) is a autosomal recessive disorder, which require the inheritance of two copies of mutated beta globin gene (one from each parent) to develop the symptoms.  Hence, both parents have to be beta-thalassemia minor.
The lack of beta globin will result in a life-threatening anemia. It will reduce the production of hemoglobin which is important for the body by transporting oxygen in red blood cells around the body.  

Beta Thalassemia Major is a blood disorder, also known as the Cooley’s anemia. There will be a shortage of red blood cells, which will lead to many serious complications.

Signs and symptoms will show within the first 2 years of life. Children will not gain weight and may develop jaundice. They may have enlarged spleen, heart and liver. Adolescents may experience delayed puberty.

Treatment
There is currently no cure for people affected by Beta-Thalassemia Major. Individuals with beta-thalassemia major will require frequent blood transfusion and extensive medical care to replenish red blood cell supply. They have to undergo therapy for removal of excess iron in the body due to the transfusion. The excess amount of iron-containing hemoglobin from the blood transfusions build up in the body, and will cause damage to the liver and heart, thus, leading to other liver, heart and hormone problems.