Symptoms of G6PD Deficiency
Most individuals with G6PD deficiency remain asymptomatic throughout their lives, but when symptoms occur, they manifest primarily as acute hemolytic anemia triggered by oxidative stressors such as infections, certain medications, or fava bean ingestion. 1, 2
Acute Hemolytic Crisis Symptoms
When exposed to oxidative triggers, patients develop acute hemolysis with the following manifestations:
- Jaundice (yellowing of skin and eyes) is the most common presenting sign 3, 1
- Anemia with associated fatigue and weakness 1
- Dark urine (hemoglobinuria) from red blood cell breakdown 1
- Back pain or abdominal pain during hemolytic episodes 1
- Pallor from acute anemia 2
Neonatal Presentation
Newborns with G6PD deficiency may present differently:
- Neonatal jaundice (hyperbilirubinemia) is one of the most frequent clinical manifestations, which can be severe enough to require phototherapy or exchange transfusion to prevent kernicterus 2, 4
- This typically occurs within the first few days of life 5
Chronic Manifestations (Rare)
Some G6PD variants cause ongoing symptoms:
- Chronic non-spherocytic hemolytic anemia (CNSHA) occurs with certain rare variants, causing persistent hemolysis rather than episodic crises 2, 5
- This is uncommon and related to sporadic gene mutations rather than the typical inherited variants 4
Severity Variation by Genetic Variant
The clinical presentation varies significantly based on the specific mutation:
- Mediterranean variant (Gdmed) typically causes more severe reactions with potentially life-threatening hemolysis 6, 3
- African variant (GdA-) usually produces milder, self-limited hemolysis 6, 3
- The severity depends on the degree of enzyme deficiency, with different classes assigned to various levels of deficiency 4
Common Triggers to Recognize
Symptoms appear after exposure to:
- Oxidative medications including dapsone, methylene blue, primaquine, rasburicase, and pegloticase 6, 3, 1
- Infections of any type 1, 2
- Fava beans (causing "favism") 1, 2
- Metabolic stress such as normalization of blood glucose in newly diagnosed diabetics 7
Important Clinical Caveat
G6PD deficiency should be suspected in any patient of Mediterranean, African, Indian, or Southeast Asian descent who develops acute hemolysis after medication exposure, infection, or fava bean ingestion, even without prior episodes 6, 1, 4.