Clinical Manifestations of G6PD Deficiency
Most individuals with G6PD deficiency remain completely asymptomatic throughout their entire lives until exposed to an oxidative trigger. 1, 2
Acute Hemolytic Crisis (Most Common Presentation)
The hallmark clinical presentation occurs when patients encounter oxidative stressors, triggering red blood cell destruction: 1, 2
Cardinal Symptoms of Acute Hemolysis
- Dark urine (hemoglobinuria) - often the first noticed symptom 3
- Sudden fatigue or pallor from acute anemia 3
- Jaundice (yellowing of skin and eyes) 1, 2
- Back or abdominal pain 1
- Anemia with associated weakness 1, 2
Common Triggers for Hemolytic Episodes
The three major precipitants that unmask G6PD deficiency are: 1, 2
- Medications - particularly dapsone, primaquine, methylene blue, rasburicase, and pegloticase 3, 1
- Infections - any significant infection can trigger hemolysis 1, 2
- Fava beans (broad beans) - the classic presentation known as "favism" 1, 2, 4
Neonatal Presentation
Neonatal hyperbilirubinemia is a critical early manifestation that requires urgent recognition to prevent kernicterus. 2
- Affected newborns may develop severe jaundice requiring phototherapy or exchange transfusion 2
- This can occur even without obvious oxidative exposure 2
Severity Variations by Genetic Variant
The clinical severity depends heavily on which genetic mutation is present: 3, 5
Mediterranean Variant (G6PD-B⁻)
- Causes severe, potentially life-threatening hemolysis 3
- Predominantly affects individuals from Mediterranean regions, India, and Southeast Asia 3, 5
- Requires strict avoidance of all oxidant medications 3
African Variant (GdA-)
- Typically causes milder, self-limited hemolysis 3
- Found in 10-15% of individuals of African descent 3
- Less severe reactions compared to Mediterranean variant 3
Chronic Hemolysis (Rare)
A small subset of patients with sporadic gene mutations experience ongoing chronic hemolysis rather than episodic acute crises, though this variant is uncommon. 2
Asymptomatic Carriers
Heterozygous females and males with milder variants may never develop symptoms if they avoid oxidative triggers. 1, 2 This represents the majority of G6PD-deficient individuals worldwide, explaining why many cases remain undiagnosed until an acute crisis occurs. 1
Critical Clinical Pitfall
Children of any age can develop hemolysis from contraindicated medications, and the same restrictions that apply to adults must be observed in pediatric patients. 3 Healthcare providers must maintain high clinical suspicion in at-risk ethnic populations (Mediterranean, African, Indian, or Southeast Asian descent) who present with unexplained hemolysis, especially following new medication exposure or infection. 5, 1