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usmle step 2 ck

G6PD Deficiency

X-linked enzyme deficiency causing episodic oxidative hemolysis after infections, fava beans, or oxidant drugs

Review date
reviewed 2026-05-04
Reading time
7 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Hematology & Oncologycommonlong-term-condition
On this page
Condition details
Hematology & Oncology
common
7 min read
reviewed 2026-05-04
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About This Page

This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

  • G6PD deficiency reduces NADPH and glutathione regeneration, making RBCs vulnerable to oxidative stress
  • Hemolysis is episodic after infection, fava beans, or oxidant drugs such as dapsone, primaquine, rasburicase, nitrofurantoin, and sulfonamides
  • Peripheral smear shows bite cells; supravital stain shows Heinz bodies
  • Testing during an acute episode can be falsely normal because older deficient RBCs have already hemolyzed
  • Treatment is trigger avoidance and supportive care; severe episodes may require transfusion

Overview

Glucose-6-phosphate dehydrogenase deficiency is an X-linked disorder of the pentose phosphate pathway. Without adequate NADPH, RBCs cannot maintain reduced glutathione and are damaged by oxidative stress. Macrophages remove denatured hemoglobin inclusions, creating bite cells. Infection is the most common trigger.

Epidemiology

G6PD deficiency is common globally and occurs in populations with ancestry from Africa, the Mediterranean, the Middle East, and parts of Asia. It confers partial protection against malaria. Males are more commonly affected because of X-linked inheritance.

Clinical Features

Symptoms
Sudden fatigue, jaundice, dark urine, and back or abdominal pain after trigger exposure
Neonatal jaundice
Symptoms often begin 24-72 hours after oxidant exposure
Severe anemia with syncope, chest pain, or dyspnea
Signs
Jaundice and scleral icterus
Pallor and tachycardia during hemolytic episode
Dark urine from hemoglobinuria
Usually no splenomegaly between episodes

Investigations

First-line
CBC with reticulocyte countAnemia with elevated reticulocytes during hemolysis
Hemolysis labsHigh LDH, high indirect bilirubin, low haptoglobin, hemoglobinuria
Peripheral smearBite cells and blister cells; Heinz bodies seen with supravital stain
Second-line
G6PD enzyme assayConfirms diagnosis, but may be falsely normal during acute hemolysis; repeat after recovery
Direct antiglobulin testNegative; helps distinguish from autoimmune hemolytic anemia
Medication and exposure reviewDapsone, primaquine, rasburicase, sulfonamides, nitrofurantoin, fava beans, naphthalene
Specialist
Genetic testingRarely needed clinically; can be useful in complex family counseling or equivocal enzyme testing

Management

ASH hemolytic anemia education and standard US hematology practice
1
Acute hemolysis
  • Stop the triggering medication or remove exposure
  • Treat infection aggressively when present
  • Supportive care with hydration and monitoring for AKI
  • Transfuse packed RBCs if severe symptomatic anemia or hemodynamic compromise
2
Prevention
  • Avoid known oxidant drugs: dapsone, primaquine, tafenoquine, rasburicase, nitrofurantoin, and many sulfonamides when alternatives exist
  • Avoid fava beans and naphthalene exposure
  • Document deficiency clearly in the medical record
3
Neonatal care
  • Monitor bilirubin closely in affected newborns
  • Phototherapy or exchange transfusion if severe hyperbilirubinemia according to pediatric thresholds

Complications

  • Acute hemolytic anemia: Can be severe after high oxidative exposure
  • Neonatal kernicterus: Severe unconjugated hyperbilirubinemia if untreated
  • Acute kidney injury: Hemoglobinuria and severe intravascular hemolysis
  • Medication harm: Rasburicase can trigger life-threatening hemolysis and methemoglobinemia
USMLE Step 2 CK Exam Tips
  • 1Bite cells on smear after sulfa drug or fava beans = G6PD deficiency
  • 2Heinz bodies require supravital stain
  • 3Most common trigger is infection, not medication
  • 4G6PD level can be falsely normal during acute hemolysis; repeat later
  • 5Do not give rasburicase to a patient with G6PD deficiency
  • 6Coombs test is negative in G6PD hemolysis

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Verified Sources & References

ASH Clinical Practice Guidelines and Education
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