Glucose-6-phosphate dehydrogenase deficiency is an inherited condition caused by a defect or defects in the gene that codes for the enzyme, glucose-6-phosphate dehydrogenase (G6PD). It can cause hemolytic anemia, varying in severity from life-long anemia, to rare bouts of anemia to total unawareness of the condition. The episodes of hemolytic anemia are usually triggered by oxidants, infection, or by eating fava beans.
G6PD deficiency is the most common enzyme deficiency in the world, with about 400 million people living with it. It is most prevalent in people of African, Mediterranean, and Asian ancestry. The incidence in different populations varies from zero in South American Indians to less than 0.1% of Northern Europeans to about 50% of Kurdish males. In the United States, it is most common among African American males; about 11 to 14% are G6PD-deficient.
G6PD deficiency is a recessive sex-linked trait. Thus, males have only one copy of the G6PD gene, but females have two copies. Recessive genes are masked in the presence of a gene that encodes normal G6PD. Accordingly, females with one copy of the gene for G6PD deficiency are usually normal, while males with one copy have the trait.
G6PD is present in all human cells but is particularly important to red blood cells. It is required to make NADPH in red blood cells but not in other cells. It is also required to make glutathione. Glutathione and NADPH both help protect red blood cells against oxidative damage. Thus, when G6PD is defective, oxidative damage to red blood cells readily occurs, and they break open as a result. This event is called hemolysis, and multiple hemolyses in a short time span constitute an episode of hemolytic anemia.
As of 1998, there are almost 100 different known forms of G6PD enzyme molecules encoded by defective G6PD genes, yet not one of them is completely inactive. This suggests that G6PD is indispensable. Many G6PD defective enzymes are deficient in their stability rather than their initial ability to function. Since red blood cells lack nuclei, they, unlike other cells, cannot synthesize new enzyme molecules to replace defective ones. Hence, we expect young red blood cells to have new, functional G6PD and older cells to have non-functioning G6PD. This explains why episodes of hemolytic anemia are frequently self-limiting; new red blood cells are generated with enzymes able to afford protection from oxidation.
The geographic distribution of G6PD deficiency, allowing for migration, coincides with the geographic distribution of malaria. This fact and survival statistics suggest that G6PD deficiency protects against malaria.
Glucose-6-phosphate dehydrogenase deficiency is also known as G6PD deficiency, favism, and primaquine sensitivity.
Lorraine Lica PhD, The Gale Group Inc., Gale, Detroit,