Genetic Mutation:
1 G6PD deficiency is caused by mutations in the G6PD gene located on the X chromosome.
2 Since it's X-linked, males are typically more affected, while females can be carriers or affected depending on X-inactivation patterns.
Enzyme Role:
1 G6PD is crucial in the pentose phosphate pathway, which helps protect red blood cells (RBCs) from oxidative damage.
2 It produces NADPH, a coenzyme essential for maintaining the level of reduced glutathione in cells.
Oxidative Stress:
1 Without sufficient G6PD, RBCs cannot generate enough NADPH.
Reduced glutathione levels fall, leaving RBCs vulnerable to oxidative stress.
Hemolysis:
1 Exposure to certain triggers (e.g., infections, certain medications, fava beans) increases oxidative stress.
2 The lack of NADPH and reduced glutathione leads to the oxidation of hemoglobin and other cellular components, causing RBCs to become rigid and prone to rupture (hemolysis).
Hemolytic Anemia:
1 The destruction of RBCs leads to hemolytic anemia, characterized by fatigue, jaundice, dark urine, and pallor.
2 The body tries to compensate by increasing erythropoiesis (production of new RBCs), but this may not be sufficient during acute episodes.
Bilirubin Production:
1 Hemolysis results in the release of hemoglobin, which is broken down into bilirubin.
2 Excessive bilirubin can lead to jaundice and, in severe cases, kernicterus in newborns.
Splenic Sequestration:
1 The spleen removes damaged RBCs from circulation, further contributing to anemia.
2 Chronic hemolysis can lead to splenomegaly (enlarged spleen).