Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymatic disorder of red blood cells (RBCs), affecting over 400 million people worldwide. It is an X-linked recessive disorder.

G6PD plays a critical role in the pentose phosphate pathway by generating NADPH, which protects RBCs from oxidative damage. Deficiency results in vulnerability to oxidative stress, leading to episodic hemolytic anemia.

Hemolysis is typically triggered by:

• Infection

• Oxidative drugs

• Certain foods (e.g., fava beans)

Pathophysiology

G6PD deficiency leads to:

• Reduced NADPH production

• Decreased glutathione regeneration

• Oxidative damage to hemoglobin

• Formation of Heinz bodies

• Splenic removal of damaged RBCs (bite cells)

• Intravascular and extravascular hemolysis

Risk Factors

• Male sex

• Family history

• African, Mediterranean, Middle Eastern, or Asian ancestry

• Exposure to oxidative stressors

Clinical Presentation

Most individuals are asymptomatic until exposed to oxidative stress.

A. Acute Hemolytic Episode

• Sudden pallor

• Jaundice

• Dark (cola-colored) urine

• Fatigue

• Back or abdominal pain

• Tachycardia

B. Neonatal Presentation

• Prolonged neonatal jaundice

• Risk of kernicterus

C. Chronic Hemolysis (Rare Variants)

• Chronic nonspherocytic hemolytic anemia

Common Triggers

A. Drugs

• Sulfonamides

• Nitrofurantoin

• Dapsone

• Primaquine

• Chloroquine (high doses)

• Proguanil

• Aspirin (high doses)

B. Foods

• Fava beans (favism)

C. Infections

• Viral or bacterial infections (most common trigger)

Diagnostic Criteria

Diagnosis is based on:

1. Clinical history of episodic hemolysis

2. Laboratory evidence of hemolysis

3. Confirmatory enzyme assay

Investigations

A. Laboratory Findings During Hemolysis

• Decreased hemoglobin

• Elevated reticulocyte count

• Elevated indirect bilirubin

• Elevated LDH

• Reduced haptoglobin

B. Peripheral Blood Smear

• Normocytic normochromic anemia

• Bite cells

• Heinz bodies (on supravital stain)

• Occasionally spherocytes

Note: Ham’s test is NOT used for G6PD deficiency (it is for PNH).

C. Confirmatory Test

• Quantitative G6PD enzyme assay

  • Best performed after recovery from acute hemolysis

Management

Management is primarily supportive.

A. Non-Pharmacological

• Immediate withdrawal of offending agent

• Avoidance of known triggers

• Adequate hydration

• Monitor renal function

Blood Transfusion

• Packed red blood cells (10 mL/kg over 6–8 hours) in severe anemia

• Monitor hemoglobin after transfusion

B. Pharmacological

• Folic acid 5 mg PO daily for 1 month (supports erythropoiesis)

There is no specific enzyme replacement therapy.

Complications

• Acute renal failure

• Severe anemia

• Neonatal kernicterus

• Chronic hemolytic anemia (rare)

Prognosis

• Excellent if triggers are avoided

• Hemolytic episodes are usually self-limited

• Lifelong condition

Prevention

• Patient education

• Screening in high-risk populations

• Avoid oxidative drugs and fava beans

• Neonatal screening programs

• Genetic counseling

Counseling Points

• Inform healthcare providers of diagnosis

• Carry medical identification

• Avoid self-medication