How do I explain Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency to patients?

How to Explain G6PD Deficiency to Patients

G6PD deficiency is an inherited condition where red blood cells lack enough of a protective enzyme, making them vulnerable to breaking apart (hemolysis) when exposed to certain triggers like specific medications, infections, or foods like fava beans.

What G6PD Deficiency Is

• G6PD is a "housekeeping" enzyme present in all cells that produces NADPH, a substance that protects cells—especially red blood cells—from oxidative damage 1
• The deficiency arises from inherited mutations that reduce enzyme stability, causing enzyme levels to drop as red blood cells age 1
• This is the most common inherited enzyme disorder worldwide, affecting approximately 400 million people 2
• It follows an X-linked inheritance pattern, meaning it predominantly affects males, though females can be carriers or affected if they inherit two copies 3, 4

Who Gets It

• The condition is most common in people of Mediterranean, African, Middle Eastern, Indian, and Southeast Asian descent 5, 6
• In African populations, 10-15% of individuals carry the African variant (GdA-) 7
• The Ashkenazi Jewish population has relatively higher prevalence for certain genetic conditions, though G6PD specifically varies by ethnic background 8
• The condition has now migrated globally and should be considered a worldwide disease 2

What Happens in G6PD Deficiency

• Most people with G6PD deficiency are completely asymptomatic under normal conditions and live normal lives 1, 4
• Problems only occur when red blood cells face oxidative stress they cannot handle due to the enzyme deficiency 2
• When triggered, red blood cells break apart (hemolyze), causing acute hemolytic anemia 1

When Problems Occur

Three Main Triggers:

1. Certain medications - particularly antimalarials (primaquine), antibiotics (dapsone, sulfonamides), and other oxidant drugs 5, 6
2. Infections - various bacterial and viral infections can trigger hemolysis 1, 2
3. Fava beans - ingestion causes a condition called "favism" in susceptible individuals 1, 2

Two Critical Life Periods:

• Newborn period: Severe jaundice can develop, potentially requiring phototherapy or exchange transfusion 5
• Childhood and beyond: Acute hemolytic crises when exposed to triggers 9

Important Variant Differences

The severity depends on which genetic variant you have:

• Mediterranean variant (Gdmed): Causes life-threatening hemolysis requiring strict avoidance of all oxidant drugs 7, 6
• African variant (GdA-): Produces milder, self-limited hemolysis that typically stops on its own 5, 7
• Patients with 30-70% enzyme activity and non-Mediterranean variants may tolerate some medications with close monitoring 5, 6

Medications to Absolutely Avoid

These drugs are strictly contraindicated and can cause severe, life-threatening hemolysis:

• Primaquine (antimalarial) 7, 6
• Dapsone (antibiotic) 5, 7
• Rasburicase (for tumor lysis syndrome) 5, 6
• Methylene blue (methylthioninium chloride) 5, 7, 6
• Sulfonamide antibiotics 6

Medications That Are Safe

These medications have NOT been shown to cause hemolytic crises and can be used safely:

• Benzodiazepines (for anxiety) 2
• Codeine and codeine derivatives (for pain) 2
• Propofol (anesthesia) 2
• Fentanyl and other opioids (for pain) 2
• Ketamine (anesthesia) 2
• Artemisinin-based combination therapies for malaria treatment 7
• Chloroquine/hydroxychloroquine in standard doses appear relatively safe 7

What to Watch For (Signs of Hemolysis)

If exposed to a trigger, watch for these symptoms and seek immediate medical attention:

• Dark or tea-colored urine
• Yellowing of skin or eyes (jaundice)
• Extreme fatigue or weakness
• Rapid heartbeat
• Shortness of breath
• Pale skin
• Back or abdominal pain

Essential Actions for Patients

1. Always inform every healthcare provider (doctors, dentists, pharmacists) about your G6PD deficiency before receiving any medication 2
2. Carry a medical alert card or wear a medical alert bracelet 2
3. Screen first-degree relatives (parents, siblings, children) for G6PD deficiency 5
4. Avoid fava beans completely 2
5. Seek immediate medical attention if you develop dark urine or jaundice after taking a new medication or during an infection 2

Special Considerations for Women

• Pregnant women with G6PD deficiency can safely use chloroquine for malaria prevention, as it does not harm the fetus 7
• However, the fetus may be G6PD-deficient even if the mother is normal, so primaquine and tafenoquine are contraindicated during pregnancy regardless of maternal G6PD status 7
• Women who are carriers (heterozygous) may have variable enzyme levels and require quantitative testing to determine their risk 5

Testing Recommendations

• If you have Mediterranean, African, Indian, or Southeast Asian ancestry, screening is recommended before starting any oxidant drugs 5, 6
• For newborns with severe jaundice not responding to phototherapy, G6PD testing should be performed 5
• Avoid testing during or immediately after a hemolytic episode, as results may be falsely normal 5

Key Takeaway

The most effective management strategy is prevention—avoid known triggers, inform all healthcare providers of your condition, and you can live a completely normal, healthy life 2