Cause of alpha thalassemia:
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
Deletion of alpha genes
Deletion of beta genes
Excess of alpha genes
Single amino acid substitution in alpha chain
Thalassemia