Overview
Glucose-6-phosphate dehydrogenase is an essential enzyme in the hexose monophosphate shunt that protects red blood cells from oxidative damage. It generates NADPH, which maintains glutathione in its reduced form and helps neutralize reactive oxygen species. G6PD deficiency is an inherited X-linked recessive disorder that results in reduced or absent enzyme activity, making red blood cells vulnerable to oxidative stress and leading to episodic hemolysis.
Symptoms
Individuals with G6PD deficiency may remain asymptomatic until exposed to oxidative stress. During hemolytic episodes, patients commonly present with pallor, jaundice, dark tea-colored urine, fatigue, shortness of breath, tachycardia, and back or abdominal pain. In severe cases, acute hemolytic anemia may develop, and newborns can present with neonatal jaundice. Between hemolytic crises, most individuals remain clinically normal.
Causes
G6PD deficiency is caused by genetic mutations affecting the G6PD enzyme, leading to impaired red cell protection against oxidative injury. Exposure to triggers such as infections, certain drugs like antimalarials, sulfonamides, dapsone, aspirin, and nitrofurantoin, as well as foods such as fava beans, increases oxidative stress and causes red cell destruction. Oxidative damage results in the formation of Heinz bodies and bite cells, leading to premature hemolysis.
Risk Factors
Risk factors include male sex due to X-linked inheritance and belonging to populations with high prevalence, such as African, Mediterranean, and Asian regions. Infections, use of oxidant drugs, ingestion of fava beans, and exposure to certain chemicals increase the risk of hemolytic episodes. Heterozygous females may show variable enzyme activity due to mosaicism.
Prevention
Although G6PD deficiency cannot be cured, hemolytic episodes can be prevented by avoiding known triggers. Early diagnosis through enzyme assays allows patient education and prevention of exposure to harmful drugs and foods. Prompt treatment of infections and careful drug selection reduce the risk of hemolysis. Newborn screening and genetic counseling help identify affected individuals early and prevent complications.
