Paroxysmal nocturnal hemoglobinuria (PNH) occurs due to a somatic mutation in which gene, and what is the direct consequence of this mutation?
- A G6PD — reduced NADPH, increased oxidative hemolysis
- B PIGA — deficiency of GPI anchor synthesis, loss of CD55 and CD59 ✓
- C UROS — defective uroporphyrinogen III synthase, porphyrin accumulation
- D ALAS2 — decreased heme synthesis, microcytic anemia
Correct answer: B. PIGA — deficiency of GPI anchor synthesis, loss of CD55 and CD59
Explanation
PNH results from a somatic mutation in the X-linked PIGA gene in a hematopoietic stem cell, impairing synthesis of the glycosylphosphatidylinositol (GPI) anchor. This causes deficiency of GPI-anchored complement regulatory proteins CD55 (DAF) and CD59 (MIRL), leaving RBCs vulnerable to complement-mediated intravascular lysis, particularly in acidic conditions at night. G6PD deficiency causes episodic hemolysis with oxidant stress. UROS and ALAS2 mutations cause porphyrias and sideroblastic anemia, respectively.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.