G 6 P D d e f i c i e n c y
Pathogenesis
• G6PD catalyzes the initial step in the pentose phosphate pathway of
glycolysis.
• Need G6PD to reduce NADP to NADPH, which keeps glutathione in the
reduced state (reduced glutathione detoxifies hydrogen peroxide and other
organic peroxides).
• Gene for G6PD is on the X chromosome (therefore, males usually have full
disease expression; heterozygous females are clinically normal).
• Very common in certain populations (10% of black men in US have the
gene!). Highest incidence is in populations in which malaria was endemic.
G6PD deficiency is thought to confer a selective advantage against malaria
infection:
• Malaria bug infects the red cell, but then both red cell and bug die.
• G6PD-deficient red cells lack the ribose derivatives bugs need to grow.
• Why are G6PD-deficient cells destroyed prematurely?
• Red cell can't reduce the H O /other nasties made during cell life
• Sulfhydryl groups/disulfide bonds are attacked
• Heme is liberated from globin
• Globin is denatured (making Heinz body); sticks to red cell membrane
• Membrane plasticity compromised
• Red cells detained in passage through liver/spleen, where macrophages
remove Heinz bodies.
Clinical findings
In most affected individuals, severe hemolysis occurs only after exposure to oxidizing agents (antimalarial drugs, sulfonamides, H O , even aspirin in some patients) or infection (unknown mechanism).
Morphology
• In absence of exposure to offending agents, most patients have no anemia.
• After exposure, get acute hemolytic episode:
• Cell fragments, microspherocytes, and bite cells (caused by recent
pitting of Heinz bodies).
• Supravital staining will reveal Heinz bodies (these decrease in number as
Hgb bottoms out, because younger cells have greater G6PD activity!).
• In 5 days, start seeing reticulocytes.
• Hemolysis is self-limiting, with spontaneous resolution in 1 week
(kill off old red cells first; younger ones have greater G6PD activity)
Therapy
• Avoid taking offending drugs or drinking H O .
• Rare patients may require more active intervention (e.g., red cell transfusion).
