What are the typical presentations of G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency?

Typical Presentations of G6PD Deficiency

G6PD deficiency typically presents with acute hemolytic anemia characterized by pallor, dark red urine, and jaundice occurring 24-72 hours after exposure to oxidative stressors such as certain foods (especially fava beans), medications, or infections. 1, 2

Clinical Manifestations

Acute Hemolytic Episodes

• Primary manifestations:

  • Pallor (100% of cases) 2
  • Dark red/cola-colored urine (89.6% of cases) 2
  • Jaundice (87.8% of cases) 2
  • Fatigue and weakness
  • Abdominal or back pain
  • Shortness of breath

• Laboratory findings during hemolysis:

  • Normocytic normochromic anemia
  • Reticulocytosis
  • Presence of Heinz bodies in red blood cells
  • Elevated indirect bilirubin
  • Decreased haptoglobin
  • Hemoglobinuria

Common Triggers of Hemolysis

1. Dietary triggers (most common - 83.4% of cases) 2:

   • Fava beans (32.6%)
   • Falafel (19.4%)
   • Other legumes: chickpeas (10.8%), broad beans (7.6%), green peas (4.4%)

2. Infections (12.4% of cases) 2:

   • Pneumonia (3.4%)
   • Tonsillitis (3.2%)
   • Typhoid fever (2.8%)
   • Hepatitis A (1.8%)
   • Urinary tract infections (1.2%)

3. Medications (4.2% of cases) 2:

   • NSAIDs: diclofenac (2.4%), ibuprofen (0.8%), aspirin (0.4%)
   • Antimicrobials: co-trimoxazole (0.4%), nitrofurantoin (0.2%)
   • Other high-risk medications not to be used 1, 3:
     • Primaquine
     • Dapsone
     • Rasburicase
     • Methylene blue
     • Sulfonamides

Special Population Presentations

Neonatal Presentation

• Neonatal jaundice: Can be severe and lead to kernicterus if not promptly treated 4
• Hyperbilirubinemia may develop rapidly in the first week of life
• Can occur in both males and females, though more common in males

Chronic Nonspherocytic Hemolytic Anemia

• Rare presentation seen with certain G6PD mutations 5
• Characterized by chronic hemolysis without exposure to known triggers
• May present with chronic anemia, splenomegaly, and gallstones

Infection Susceptibility

• Severe G6PD deficiency can lead to impaired neutrophil function 6
• May present with recurrent bacterial infections similar to chronic granulomatous disease
• Impaired neutrophil extracellular trap (NET) formation

Demographic Patterns

• Gender distribution: Males are more commonly affected (93.2% males vs 6.8% females in large studies) 2
• Age at first presentation: Most commonly between 1-3 years of age (92% of cases) 2
• Geographic distribution: Highest prevalence in Africa, Mediterranean region, Middle East, Southeast Asia, and Oceania 3, 5

Severity Spectrum

• Mild to moderate deficiency: Hemolysis typically occurs only with significant oxidative stress
• Severe deficiency: May present with chronic hemolytic anemia or more frequent/severe hemolytic episodes
• Enzyme activity correlation: Most common G6PD enzyme level during acute episodes is 3-4 U/gm Hb (59.2% of cases) 2

Clinical Pearls and Pitfalls

• Hemolysis typically occurs 24-72 hours after exposure to triggers (average 36 hours) 2
• Female carriers (heterozygotes) can also experience hemolysis due to random X-chromosome inactivation 1
• Medications like amoxicillin, though generally considered safe, have rarely been reported to trigger hemolysis in G6PD-deficient individuals 7
• The FDA label for primaquine specifically warns about the risk of hemolytic anemia in G6PD-deficient patients and recommends G6PD testing before administration 3