- Clinical science
Glucose-6-phosphate dehydrogenase (G6PD) deficiency leads to an impaired regeneration of reduced glutathione, an important antioxidant, which makes RBCs more susceptible to oxidative stress and can result in episodic hemolytic anemia. The condition is inherited in an X-linked recessive pattern and is the most common human enzyme deficiency worldwide. It primarily affects males of African, Asian, and Mediterranean descent. G6PD is usually asymptomatic, but a sudden surge in oxidative stress (e.g., after infection, consumption of fava beans, or various drugs) may lead to a life-threatening hemolytic crisis. Diagnostic findings include signs of intravascular hemolysis (e.g., normocytic anemia, ↑ LDH, and ↓ haptoglobin), Heinz bodies, and bite cells on blood smear. Management mainly consists of preventing hemolysis by avoiding triggers.
- G6PD deficiency is the most common human enzyme deficiency.
- Prevalence: ∼ 400 million worldwide
- Affects primarily males of African, Mediterranean, and Asian descent
Epidemiological data refers to the US, unless otherwise specified.
- X-linked recessive
- G6PD is the rate-limiting enzyme of the pentose phosphate pathway (also known as the hexose monophosphate shunt). This pathway yields NADPH; , which is essential for converting oxidized glutathione back to its reduced form; . Reduced glutathione is capable of neutralizing reactive oxygen species (ROS) and free radicals and therefore protecting RBCs from oxidative damage. In the absence of reduced glutathione (e.g., due to G6PD deficiency), RBCs become susceptible to oxidative stress that can damage erythrocyte membranes, resulting in intravascular hemolysis.
Causes of increased oxidative stress are triggers of hemolytic crisis and include:
- Fava beans
- Drugs: antimalarial drugs (e.g., chloroquine, primaquine), sulfa drugs (e.g., trimethoprim-sulfamethoxazole), nitrofurantoin, isoniazid, dapsone, NSAIDs, ciprofloxacin, chloramphenicol
- Bacterial and viral infections (severe enzymatic deficiency can inhibit respiratory burst activity due to ↓ NADPH production in phagocytes)
- Metabolic acidosis
- Most patients are asymptomatic.
- Recurring hemolytic crises may occur, especially following triggers
- Recurrent severe infections causing symptoms of
- Heinz bodies
- Bite cells
- Signs of intravascular
Screening test: fluorescent spot test
- Add glucose-6-phosphate and NAPD → measure NADPH fluorescence
- Confirmatory test: quantitative G6PD enzyme analysis
- Ideally, both tests should be performed during remission.
- Avoid triggers
- Blood transfusions should be performed only in rare, severe cases.