Cause of alpha thalassemia:
Deletion of alpha genes
Deletion of beta genes
Excess of alpha genes
Single amino acid substitution in alpha chain
Ans. a. Deletion of alpha genesCause of alpha thalassemia is deletion of alpha genes."The a-thalassemias are caused by inherited deletions that result in reduced or absent synthesis of a-globin chains.Normally, there are four a-globin genes, and the severity of a-thalassemia depends on how many a-globin genes are affected. As in b-thalassemias, the anemia stems both from a lack of adequate hemoglobin and the effects of excess unpaired non-a. chains (b, g, and d), which vary in type at different ages. In newborns with a-thalassemia, excess unpaired g-globin chains form g4 tetramers known as hemoglobin Barts, whereas in older children and adults excess b-glohin chains form b4 tetramers known as HbH. Since free b and g chains are more soluble than free a chains and form fairly stable homo tetramers, hemolysis and ineffective erythropoiesis are less severe than in b-thalassemias. A variety of molecular lesions give rise to a-thalassemia, but gene deletion is the most common cause of reduced a -chain synthesis. "- Robbins 9/e p64Ia-THALASSEMIASClinical SyndromesGenotypeClinical FeaturesMolecular GeneticsSilent carrier-/a a/aAsymptomatic; no red cell abnormalityMainly gene deletions0a-Thalassemia trait-/- a/a (Asian)Asymptomatic, like b-thalassemia minor -/a -/a (black African, Asian) HbH disease-/- -/aSevere; resembles b-thaiassemia intermedia Hydrops fetalis-/- -/-Lethal in utero without transfusions
Thalassemia