The primary defect which leads to sickle cell anemia is -

Ans. is 'b' i.e., Replacement of glutamate by valine in b chain of HBA Sickle cell anemiao Sickle cell anemia is a hereditary hemoglobinopathy, i.e., the type of disease characterized by production of defective hemoglobin.o Sickle cell anemia results from mutation in b-globin gene.o It is caused by a point mutation at the sixth position of the b-globin chain leading to subsitution of a valine residue for a glutamic acid residue resulting in sickle hemoglobin (HbS).o Sickle cell anemia is an autosomal recessive disorder.o If an individual is homozygous for the sickle cell mutation, almost all the hemoglobin in the red cell is HbS.o In heterozyogotes, only about 40% of the hemoglobin is HbS, the remainder being normal hemoglobins.Effect of HbS on RBCso In deoxygenated condition, the HbS molecules undergo polymerization and aggregation,o With continued deoxygenation, aggregated HbS molecules assemble into long needle-like fibers writhin red cells, producing a distorted sickle or holly-leaf shape.o Sickling of red cells is reversible initialy, i.e., with oxygenation, HbS depolymerizes and cell shape normalizes,o Howrever, with repeated episodes of deoxygenation and sickling, membrane damage occurs and cells become irreversibly sickled, and retain their abnormal shape even when full oxygenated,o With membrane damage water comes out of the cell resulting in intracellular dehydration -| MCHC.o Due to membrane damage, sickle red cells become abnormally sticky - responsible for microvascular occlusions.Remembero Irreversible sickle cells are responsible for hemolytic anemia.o Reversible sickle cells are responsible for vasoocclusive symptoms.