Glucose-6-Phosphate Dehydrogenase Deficiency

Overview
  • Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD Deficiency) is a cause hemolytic anemia triggered by exposure to oxidizing chemicals that occurs in patients with an inherited defect in the enzyme Glucose 6 Phosphate Dehydrogenase (G6PD).
Etiology
  • Deficiency of G6PD is caused by mutations of the G6PD gene which is located on the X Chromosome; consequently, G6PD is inherited as a X-linked recessive trait and is thus more common in men. The mutation is particularly prevalent among those with Asian, Middle Eastern, or African ancestry.
Pathogenesis
  • G6PD is an enzyme that plays a role in the pathway that generates glutathione, a small molecule responsible for protecting cells, particularly erythrocytes, from oxidant injury. Most individuals with G6PD deficiency have sufficient G6PD activity at baseline to avoid pathology. However, under conditions of oxidant stress, the limited reserves of glutathione are overwhelmed and free radical cell injury occurs, primarily affecting hemoglobin which upon becoming oxidized precipitates within erythrocytes. Precipitated Hb can directly hemolyze the RBC or can alternatively deform its membrane such that the erythrocyte is destroyed by cells of the reticuloendothelial system.
Morphology
  • The classic finding of G6PD Deficiency is that of intra-erythrocytic "Heinz Bodies" which represent collections of precipitated oxidized hemoglobin. These Heinz bodies can locally deform the erythrocyte membrane, leading to their localized removal by cells of the reticuloendothelial system, leaving erythrocytes that look like a "Bite" has been taken out of them, hence termed "Bite Cells".
Clinical Consequences
  • Hemolysis in G6PD deficiency is typically transient and follows infections or ingestion of oxidizing substances such as certain antibiotics (classically bacterial metabolism inhibitors such as bactrim) or Fava Beans. In addition to the symptoms of anemia (see page) patients may become transiently jaundiced due to unconjugated hyperbilirubinemia and may display splenomegaly due to extravascular hemolysis within the spleen.