Question

Paroxysmal nocturnal hemoglobinuria (PNH) is associated with deficiency of:

• A. DAF (Decay accelerating factor)
• B. MIRL (Membrane inhibitor of reactive lysis)
• C. GPI anchored protein (Glycosyl phosphatidyl inositol anchored proteins)
• D. LFA (Lymphocyte function associated antigen)

Hint:

The missing anchor explains loss of both CD55 and CD59 at once.

Answer 1

The Correct Option is C

Step 1: Recall the basic defect in PNH. PNH is an acquired clonal stem cell disorder caused by a somatic mutation in the PIGA gene. This gene is needed to make the glycosyl phosphatidyl inositol (GPI) anchor.
Step 2: Understand the GPI anchor. The GPI anchor is a small lipid stalk that fixes many surface proteins onto the red cell membrane. If the anchor cannot be made, every protein that depends on it is lost from the cell surface.
Step 3: Connect the anchor to hemolysis. Two of the lost proteins are complement regulators: DAF (CD55) and MIRL (CD59). Without CD55 and CD59 the red cells cannot block complement, so complement attacks them and causes intravascular hemolysis, especially at night, producing hemoglobinuria.
Step 4: Choose the best single answer. DAF and MIRL are both deficient, but they are deficient only because the upstream GPI anchor is missing. The root and most complete answer is the GPI anchored protein defect, which explains the loss of both regulators at once.
Step 5: Reject the wrong option. LFA is a leukocyte adhesion molecule and has no role in PNH hemolysis, so option D is wrong.
Conclusion: The single best answer is deficiency of the GPI anchored protein. The answer is option C.