THALASSEMIAS

THALASSEMIAS are the group of hereditary disorders of hemolysis characterized by an imbalance in the synthesis of Globin chains of hemoglobin. Hemoglobin contains 2α and 2β globin chains. The synthesis of individual chains is coordinated in such a way that both chains combine.

Defects of Thalassemia:

• Deletion or substitution of genes.
• mRNA gets unstable.
• Defective chain synthesis.
• Premature chain termination.

 α – Thalassemia is caused by either due to decreased synthesis or total absence of the α globin chain. Basically there are four types of α globin chains two on each of chromosome 16.

Important characteristics:

1. Alpha Thalassemia trait is caused by loss of 2 genes from each gene pair.
2. Silent carrier due to loss of any 1 of the 4 globin genes.
3. Hemoglobin H is a disorder caused due to loss of 3 genes.
4. Hydrops fetalis (most severe form of the disease due to absence of all the 4 genes) allows the fetus to survive only until birth.

In case of fetus, since Alpha globins can not be synthesized, formation of gamma tetramers take place producing new born baby called Hb Bart and as such hemoglobin lacks heme heme interaction producing hyperbolic oxygen dissociation curve which can not deliver sufficient oxygen to the tissues causing death of the fetus.

β Thalassemia

Caused due to decreased synthesis or total absence of the formation of beta globin chains. Production of alpha globin chain continues to be normal alpha globin tetramers that undergo precipitation causing premature death of the erythrocytes.

This variety of Thalassemia is of 2 types:

• β Thalassemia major A homozygous state with defective synthesis of beta globin. The offsprings born with such defect are healthy at birth since beta globin is not synthesized during the development of the fetus. But they become severely anemic within 2 or 3 years after birth and may die. These children require frequent blood transfusion. Iron overload can lead to death.
• β Thalassemia minor.

A heterozygous state with a defect in only one of the two beta globin gene pairs on chromosome 11. This is called beta Thalassemia trait which is usually asymptomatic. This condition is curable to a certain degree.