Thalassemia

Thalassemias are common blood disorders that appear worldwide. They occur most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia. Patients are characterized by reduced hemoglobin synthesis and various degrees of anemia.

The main 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.

Thalassemias are classified according to which chain of the hemoglobin molecule is affected. In α-Thalassemias, production of the α globin chain is affected, while in β-Thalassemia, production of the β globin chain is affected.

The disease is inherited in an autosomal recessive manner, which means that when both parents are carriers, there is a 25% probability that they will have an affected child.

Beta thalassemia is caused by mutations in the beta-globin (HBB) gene. Beta-globin is a component of hemoglobin. Some mutations in the HBB gene prevent the production of any beta-globin (beta-zero (B⁰) thalassemia), while other HBB gene mutations allow synthesis of reduced amounts of beta-globin (beta-plus (B⁺) thalassemia).

Three main types of beta-Thalassemia have been described according to the clinical severity: minor, intermedia and major.

A lack of beta-globin leads to a reduced amount of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. The low number of mature red blood cells leads to anemia and other associated health problems, like splenomegaly, hepatomegaly, enlarged heart, dysmorphic bones and delayed development in people with beta thalassemia.

The severity of alpha thalassaemia differs according to the number of mutated alpha-globin genes (a normal individual has four functional alpha-globin genes). People with one mutated gene are asymptomatic and those with two mutated genes have mild anemia. Patients with three mutated genes (have only one functional alpha-globin gene) develop hemoglobinopathy H (HbH). HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). Some affected individuals also have bone changes. The features of HbH disease usually appear in early childhood. The more severe type, alpha-Thalassaemia major, is also known as hemoglobin Bart or hydrops fetalis syndrome. Most affected fetuses suffer embryonic or early neonatal death.

Beta thalassemia patients are in need of frequent blood transfusions to maintain adequate Hb levels. Long-term transfusion of red cell concentrates results in iron overload, which has negative impact on cardiac and endocrine function and leads to increased mortality. These patients are also under iron chelation therapy, to remove excess iron from the body.

In most cases the diagnosis can be achieved by a thorough hematologic exmination. This has to be carried out in a specialised center with expirienced staff. The hematologic analysis results are necessary and important in order to decide the specific molecular analysis that has to be carreid out in order to diagnose patients and detect carriers of the disease.

Preventing the birth of an affected child is very important because there is still not a broadly available treatment for the disease. When both members of a couple are carriers of the disease thay can choose between prenatal diagnosis (molecular diagnosis made on CVS collected between 10-12th week of gestation or amniotic fluid cells collected after the 16th week of gestation) or preimplantation genetic diagnosis (PGT-M).

Genesis Genoma Lab offers 3 different tests in order to diagnose patients and detect carriers of  Thalassemia: