**Core Concept**
Glucose-6-phosphate dehydrogenase (G6-PD) deficiency is a genetic disorder affecting the red blood cell's ability to maintain redox balance. The enzyme G6-PD protects cells from oxidative damage by generating NADPH, which reduces glutathione. Without sufficient NADPH, red blood cells become vulnerable to oxidative injury, leading to intravascular and extravascular hemolysis.

**Why the Correct Answer is Right**
In G6-PD deficiency, the lack of functional G6-PD results in reduced NADPH production. NADPH is essential for maintaining reduced glutathione, which neutralizes reactive oxygen species. When exposed to oxidative stress—such as certain drugs (e.g., sulfonamides), fava beans, or infections—red blood cells undergo oxidative damage, leading to hemolysis. This mechanism is central to the pathophysiology of the disease.

**Why Each Wrong Option is Incorrect**
Option A: Hemoglobin defect – G6-PD deficiency does not involve abnormal hemoglobin structure; it is a metabolic defect, not a hemoglobinopathy.
Option C: Membrane defect – The primary issue is not membrane integrity but metabolic vulnerability to oxidation.
Option D: Vitamin B12 deficiency – This causes megaloblastic anemia and is unrelated to G6-PD deficiency pathophysiology.

**Clinical Pearl / High-Yield Fact**
G6-PD deficiency is the most common inherited red blood cell disorder and is triggered by oxidative stress. A classic trigger is fava bean ingestion (favism), and patients should avoid oxidizing agents and certain medications.

✓ Correct Answer: B. Oxidative stress