G6PD Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme disorder in the world, affecting an estimated 400 million people globally. It is X-linked recessive, meaning males (who carry one X chromosome) are fully affected when they carry the variant, while females are carriers who may have mild or no symptoms. G6PD enzyme protects red blood cells from oxidative stress. When deficient, red blood cells are vulnerable to rapid destruction (hemolysis) triggered by certain medications, infections, fava beans, or other oxidative stressors. Most G6PD-deficient individuals are completely asymptomatic between episodes. In Black Americans, the A- variant (G6PD A-minus) is the most prevalent form — milder than the Mediterranean variant but clinically significant when exposed to high-risk triggers.

• Dark, cola-colored, or reddish-brown urine (during hemolytic episode)
• Sudden fatigue, weakness, or pallor
• Jaundice — yellowing of skin and whites of eyes
• Back or abdominal pain during crisis
• Rapid heart rate (tachycardia) and shortness of breath (severe anemia)
• Dizziness or lightheadedness
• Neonatal jaundice (in affected newborns — may be severe)
• No symptoms between episodes for most patients

Newborn G6PD screening is performed in some U.S. states but is not universal. G6PD activity can be measured via a quantitative spectrophotometric blood test or a qualitative fluorescent spot test. Testing should be performed when the patient is not in acute hemolytic crisis — during a crisis, reticulocytes (young red cells with higher G6PD activity) can falsely normalize results. Genetic testing can confirm variant identity (A- vs. Mediterranean vs. other). First-degree relatives — especially brothers and sons — of an identified G6PD- deficient person should be tested given X-linked inheritance.

There is no curative treatment — management centers on trigger avoidance. The most important intervention is identifying and maintaining a personal list of medications and exposures to avoid (primaquine, tafenoquine, rasburicase, dapsone, methylene blue, high-dose aspirin, naphthalene/mothballs, and in some variants, fava beans). During acute hemolytic episodes, treatment is supportive: removing the triggering agent, IV hydration to protect kidneys from hemoglobin-induced damage, and blood transfusion if anemia is severe. Folate supplementation supports red blood cell recovery. Medical alert bracelets are strongly recommended. Carrying an updated medication safety card is advised for emergency and surgical contexts.