G6PD Deficiency

Summary

G6PD deficiency is a common genetic disorder that impairs red blood cells' ability to tolerate oxidative stress, leading to episodes of hemolysis. The condition is caused by a deficiency in the enzyme G6PD, which is crucial for producing NADPH, a molecule necessary for protecting red blood cells from oxidants. Triggers such as infections, certain foods, and medications can precipitate acute hemolytic crises, characterized by symptoms like jaundice, dark urine, and anemia. Diagnosis is based on G6PD activity testing, though results may be falsely negative during acute episodes. Management involves avoiding triggers and supportive care, with blood transfusions if necessary.

Takeaways

• 😀 G6PD deficiency reduces red blood cells' ability to tolerate oxidative stress, leading to hemolytic episodes.
• 😀 During an acute hemolytic episode, the G6PD assay may give falsely negative results due to hemolyzed red blood cells.
• 😀 Oxidative injury occurs when oxidants like superoxide anion and hydrogen peroxide accumulate in red blood cells, damaging hemoglobin and proteins.
• 😀 Glutathione and glutathione peroxidase normally protect red blood cells from oxidative stress, but G6PD deficiency impairs this protective mechanism.
• 😀 Without G6PD, there is no NADPH production, which is essential for maintaining glutathione and preventing oxidative damage.
• 😀 G6PD deficiency is an X-linked genetic disorder that primarily affects males, but can also affect females who are homozygous or have Turner syndrome.
• 😀 The condition is more common in regions historically affected by malaria, such as Africa, Asia, the Mediterranean, and the Middle East.
• 😀 Clinical manifestations of G6PD deficiency include sudden onset of jaundice, pallor, dark urine, and abdominal or back pain, often within 1-3 days of exposure to oxidative stress.
• 😀 Hemolysis due to G6PD deficiency can lead to bite cells and Heinz bodies, which are visible on a peripheral blood film.
• 😀 Management of G6PD deficiency involves avoiding oxidative stress triggers, discontinuing any inciting agents, and providing supportive care like hydration and blood transfusions.
• 😀 Diagnostic testing for G6PD activity may be falsely negative during an acute episode, so retesting should be performed 6 weeks to 3 months later.

Q & A

What is G6PD deficiency?

G6PD deficiency is a common enzymatic disorder affecting red blood cells. It reduces the ability of red blood cells to tolerate oxidative stress, which can lead to hemolysis (destruction of red blood cells).

Why is G6PD important in red blood cells?

G6PD is crucial for producing NADPH, which helps protect red blood cells from oxidative stress by inactivating harmful oxidants like hydrogen peroxide and superoxide anions.

What happens when G6PD is deficient in red blood cells?

Without G6PD, NADPH cannot be produced, which impairs the ability to neutralize oxidants. This leads to oxidative damage of hemoglobin and other proteins, causing red blood cells to die prematurely.

What is the role of glutathione in preventing oxidative injury in red blood cells?

Glutathione, in conjunction with glutathione peroxidase, helps to inactivate oxidants. Glutathione itself gets oxidized in the process, but it is restored by NADPH, which is produced by G6PD activity.

What are Heinz bodies, and how do they relate to G6PD deficiency?

Heinz bodies are aggregates of denatured hemoglobin that form when hemoglobin is oxidized. These aggregates are often found in red blood cells during an acute hemolytic episode in individuals with G6PD deficiency.

What triggers acute hemolytic episodes in G6PD deficiency?

Acute hemolytic episodes in G6PD deficiency can be triggered by infections, certain foods (like fava beans), medications (such as sulfonamides, nitrofurantoin, and chloroquine), and other toxins.

How long after an acute hemolytic episode should G6PD testing be repeated?

G6PD testing should be repeated 6 weeks to 3 months after an acute hemolytic episode, as the initial test may be falsely negative due to the destruction of severely affected red blood cells.

What are some common laboratory findings in G6PD deficiency during a hemolytic episode?

During a hemolytic episode, laboratory findings may include a significant drop in hemoglobin, the presence of bite cells, microspherocytes, and blister cells on the peripheral blood film, and negative direct antiglobulin test (DAT).

Why does G6PD deficiency provide a survival advantage in certain populations?

G6PD deficiency offers a survival advantage against malaria caused by *Plasmodium falciparum*, which is why it is more common in regions historically affected by malaria, such as parts of Africa, Asia, the Mediterranean, and the Middle East.

What is the management strategy for G6PD deficiency during an acute hemolytic episode?

Management involves discontinuing the inciting agent (such as the triggering medication or food), providing supportive care, and administering hydration and blood transfusions as needed to address anemia.