Defect in membrane carbohydrate binding site for proteins required to block complement mediated RBC lysis is seen in which disorder?

Defect in membrane carbohydrate binding site for proteins required to block complement mediated RBC lysis is seen in which disorder?

• A. Paroxysmal nocturnal hemoglobinuria
• B. G6PD deficiency
• C. Cold agglutinin disease
• D. Hereditary spherocytosis

Answer: (A)

This defect involves the proteins that protect red blood cells from complement by anchoring to the membrane. In paroxysmal nocturnal hemoglobinuria, an acquired mutation disrupts the synthesis of the glycosylphosphatidylinositol (GPI) anchor, so several GPI-anchored proteins—notably CD55 (DAF) and CD59 (protectin)—are absent from the RBC surface. Without these regulators, the complement cascade can attack the cells, leading to intravascular hemolysis and hemoglobinuria, often more noticeable at night. GPI anchors are the membrane carbohydrate–binding anchors for these protective proteins, so losing them directly predisposes to complement-mediated lysis. G6PD deficiency causes oxidative damage to red cells, not a failure of complement regulation. Cold agglutinin disease is an autoimmune process that activates complement but centers on autoantibody activity rather than a loss of membrane-bound regulatory proteins. Hereditary spherocytosis stems from a structural membrane defect in the red cell cytoskeleton, leading to splenic sequestration and extravascular hemolysis, not a failure of complement protection.

This defect involves the proteins that protect red blood cells from complement by anchoring to the membrane. In paroxysmal nocturnal hemoglobinuria, an acquired mutation disrupts the synthesis of the glycosylphosphatidylinositol (GPI) anchor, so several GPI-anchored proteins—notably CD55 (DAF) and CD59 (protectin)—are absent from the RBC surface. Without these regulators, the complement cascade can attack the cells, leading to intravascular hemolysis and hemoglobinuria, often more noticeable at night. GPI anchors are the membrane carbohydrate–binding anchors for these protective proteins, so losing them directly predisposes to complement-mediated lysis.

G6PD deficiency causes oxidative damage to red cells, not a failure of complement regulation. Cold agglutinin disease is an autoimmune process that activates complement but centers on autoantibody activity rather than a loss of membrane-bound regulatory proteins. Hereditary spherocytosis stems from a structural membrane defect in the red cell cytoskeleton, leading to splenic sequestration and extravascular hemolysis, not a failure of complement protection.