Paroxymal noctural hemoglobinuria is due to –
**Core Concept**
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired, life-threatening disease characterized by the destruction of red blood cells, bone marrow failure, and the potential for blood clot formation. It is caused by a mutation in the PIGA gene, which is essential for the synthesis of the glycosylphosphatidylinositol (GPI) anchor. This anchor is necessary for the proper functioning of several proteins on the surface of red blood cells.
**Why the Correct Answer is Right**
The correct answer is related to the pathogenesis of PNH. PNH is caused by a mutation in the PIGA gene, which leads to the deficiency of GPI-anchored proteins on the surface of red blood cells. This deficiency renders the red blood cells more susceptible to destruction by the complement system, particularly by the terminal pathway of the complement cascade. The lack of GPI-anchored proteins, such as CD55 and CD59, prevents the red blood cells from being protected from complement-mediated lysis.
**Why Each Wrong Option is Incorrect**
* **Option A:** This option is incorrect as PNH is not caused by a deficiency of vitamin B12. While vitamin B12 deficiency can lead to megaloblastic anemia, it is not associated with the pathogenesis of PNH.
* **Option B:** This option is incorrect as PNH is not caused by an autoimmune response. While autoimmune diseases can lead to the destruction of red blood cells, PNH is a distinct entity caused by a genetic mutation.
* **Option C:** This option is incorrect as PNH is not caused by a viral infection. While viral infections can lead to hemolytic anemia, PNH is a rare genetic disorder caused by a mutation in the PIGA gene.
**Clinical Pearl / High-Yield Fact**
PNH is often associated with a deficiency of GPI-anchored proteins, which makes red blood cells more susceptible to complement-mediated lysis. This is why patients with PNH often have a positive sucrose lysis test, which detects the presence of GPI-anchored proteins on the surface of red blood cells.
**Correct Answer:** D. Mutation in the PIGA gene.