G6PD Deficiency – The Oxidative Stress Trap on Step 1

Imagine this Step 1 classic: A young man develops jaundice and dark urine after eating fava beans. Labs show anemia and elevated LDH. What’s going on?

You’ve just entered the world of G6PD deficiency, a high-yield genetic disorder that connects biochemistry, hematology, and pharmacology all in one go. Today’s blog walks you through what you need to know—with a KOTC visual that simplifies oxidative stress and red blood cell damage.

What Is G6PD Deficiency?

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, and its job is to protect red blood cells from oxidative damage by generating NADPH.

When G6PD is deficient, RBCs can't detoxify reactive oxygen species → leads to hemolysis.

🧠 Key buzzword: X-linked recessive disorder, most common in African, Mediterranean, or Asian descent males.

Common Step 1 Triggers for G6PD Hemolysis

🩸 1. Drugs

• Sulfa drugs (TMP-SMX)

• Anti-malarials (primaquine)

• Nitrofurantoin

• Aspirin (high dose)

• Dapsone

🦠 2. Infections

• Pneumonia

• Urinary tract infections
  (Infections generate oxidative stress → hemolysis)

🌱 3. Fava Beans

• Often mentioned in Mediterranean ancestry scenarios

• Look for food poisoning + anemia symptoms

USMLE-Style Question Breakdown

A 22-year-old man presents with fatigue and dark urine 2 days after taking trimethoprim-sulfamethoxazole. Blood smear shows bite cells. Diagnosis?

✅ G6PD Deficiency

Which of the following best explains the hemolysis in this patient?
A. Lack of reduced glutathione
B. Pyruvate kinase deficiency
C. Decreased spectrin
D. Folate deficiency

✅ Correct answer: A. Lack of reduced glutathione
(NADPH is needed to regenerate reduced glutathione!)

What You’ll See on Labs and Smear

• ↓ Hemoglobin

• ↑ LDH

• ↑ Indirect bilirubin

• ↑ Reticulocyte count

• ↓ Haptoglobin

• Peripheral smear: Heinz bodies, bite cells

💡 Heinz bodies = oxidized hemoglobin aggregates
💡 Bite cells = macrophages "biting" Heinz bodies out

Key Mnemonic: “SHe Fights Off OXidants”

• Sulfa drugs

• Heinz bodies

• Fava beans

• Oxidative stress

• X-linked inheritance

G6PD and KOTC – Making It Memorable

Visualizing red cell damage in real time helps seal this concept. The King of the Curve app uses:

• Clinical cases with genetic + lab tie-ins

• Step-style questions with trigger words highlighted

• Visual memory tools that cut through clutter

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Frequently Asked Questions (FAQs)

• How many hours should I study for the MCAT each day?

  Aim for 4-6 focused hours, ensuring you incorporate breaks to avoid burnout.

• What is the best way to handle test anxiety?

  Practice mindfulness techniques, take practice exams under realistic conditions, and maintain a balanced lifestyle.

• How can I stay motivated during the long application process?

  Set short-term goals, seek support from mentors, and reward yourself for small achievements.

• What role does exercise play in MCAT preparation?

  Regular exercise improves focus, reduces stress, and enhances overall mental clarity.

• How does King of the Curve help with MCAT preparation?

  KOTC offers personalized learning tools, gamification features, and adaptive question banks to help students stay on track without burnout.