## **Core Concept**
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells (hemolysis), bone marrow failure, and the presence of blood clots (thrombosis). It is caused by a mutation in the PIGA gene of hematopoietic stem cells in the bone marrow. This mutation leads to a deficiency of glycosylphosphatidylinositol (GPI) anchor on the surface of blood cells.

## **Why the Correct Answer is Right**
The correct answer, **C. Deficiency of GPI anchor**, is right because PNH is caused by a somatic mutation in the PIGA gene, which is essential for the synthesis of the GPI anchor. The GPI anchor is crucial for attaching many proteins to the cell membrane. Without it, red blood cells become sensitive to complement-mediated lysis, leading to intravascular hemolysis, a hallmark of PNH.

## **Why Each Wrong Option is Incorrect**
- **Option A:** Not specified, but any option not related to GPI anchor deficiency or PIGA mutation would be incorrect because they do not directly relate to the known pathophysiology of PNH.
- **Option B:** Not specified, but similar to Option A, if it does not pertain to GPI anchor deficiency or PIGA mutation, it is incorrect.
- **Option D:** Not specified, but again, if it's unrelated to the GPI anchor or PIGA mutation, it's incorrect.

## **Clinical Pearl / High-Yield Fact**
A key clinical pearl is that PNH often presents with symptoms such as hemoglobinuria (which causes the urine to appear dark or tea-colored), especially in the morning (nocturnal hemoglobinuria), due to the acidification of urine overnight which activates complement. This condition requires prompt diagnosis and treatment, often involving complement inhibitors like eculizumab, to reduce hemolysis and the risk of thrombosis.

## **Correct Answer:** C. Deficiency of GPI anchor.