Alpha- thalassemia

Ans. B: Normal HbF and normal HbA2

Alpha (+) thalassemia – genetic mutations that result in decreased production of alpha-globin usually due to the functional deletion of 1 of the 4 alpha globin genes. Based on the number of inherited alpha genes, it is subclassified into 3 general forms:

• Thalassemia (-u/ a a) is characterized by inheritance of 3 normal a-genes. These patients are referred to clinically as silent carrier of alpha thalassemia. Other names for this condition are alpha thalassemia minima, alpha thalassemia-2 trait, and heterozygosity for alpha (+) thalassemia minor. The affected individuals exhibit no abnormality clinically and may be hematologically normal or have mild reductions in red cell mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
• Inheritance of 2 normal alpha genes due to either heterozygosity for alpha (0) thalassemia (u a/ —) or homozygosity for alpha (+) thalassemia (-u/-a) results in the development of alpha thalassemia minor or alpha thalassemia-1 trait. The affected individuals are clinically normal but frequently have minimal anemia and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
• Inheritance of one normal alpha gene (-a/ —) results in abundant formation of hemoglobin H. This condition is known as ElbH disease. The affected individuals have moderate to severe lifelong hemolytic anemia, modest degrees of ineffective erythropoiesis, splenomegaly and variable bony changes
• Persons with alpha-thalassemia traits have normal HbA2 and HbF levels whereas beta- thalassemia patients have elevated HbA2

Ans. is ‘a’ i.e., Alpha chain deficiency

Alpha-thalassemia

People who do not produce enough alpha globin chain have alpha – thalassemia. Alpha globin chain is made by four genes, each gene contributes to 25% of the a-globin chains. The severity of a-thalassemia varies greatly depending on the number of a-globin genes affected –

• Silent carrier state
• Single a-globin gene is deleted. These individuals are completely asymptomatic.
• a-thalassemia trait
• Two a-globin genes are deleted. These individuals are asymptomatic with some red cell abnormalities like β-thalassemia minor.
• HbH disease
• Three genes of a-globin chain are deleted. With only one gene, the synthesis of a-chain is markedly reduced and tetramers of excess β-globin, called HbH, form. HbH has extremely high affinity for oxygen and therefore is not useful for oxygen exchange, leading to tissue hypoxia disproportionate to the level of hemoglobin. Patients have moderate to severe anemia that may require occasional blood transfusion.
• Hydrops fetalis
• There is deletion of all four a-globin genes. In the fetus, excess y-globin chains form tetramers, known as hemoglobin harts. Hemolgobin bart has such a high affinity for oxygen that it delivers almost no oxygen to tissues. Most individuals die before or shortly after birth. In utero blood transfusion have allowed the birth of children with hydrops fetalis who then require life long blood transfusions.