Glucose-6-phosphate dehydrogenase deficiency, also called G6PDD, is a very common inherited inborn error of metabolism (IEM) that is characterized by a defect in the glucose-6-phosphate dehydrogenase gene. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway. G6PD converts glucose-6-phosphate into 6-phosphoglucono-delta-lactone. This reaction supplies reducing energy to cells by maintaining high levels of NADPH inside cells, especially red blood cells. NADPH helps maintain the supply of reduced glutathione that is used to eliminate free radicals that cause oxidative damage in red blood cells. G6PDD is an X-linked genetic disorder that primarily affects males and predisposes affected individuals to red blood cell breakdown, which is called hemolysis. About 400 million people (1 in 20) have G6PDD globally and it is particularly common in certain parts of Africa, Asia, the Mediterranean, and the Middle East. Carriers of the G6PDD allele may be partially protected against malaria, which explains the higher incidence of this genetic defect in people coming from countries that have or historically had malaria. While the vast majority of affected individuals are male, females can be clinically affected due to unfavourable lyonization, where random inactivation of an X-chromosome in certain cells creates a population of G6PD-deficient red blood cells coexisting with unaffected red blood cells. As noted above, G6PDD mainly affects the redox capacity of red blood cells, which carry oxygen from the lungs to tissues throughout the body. The most common medical problem associated with G6PDD is hemolytic anemia, which occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, shortness of breath, fatigue, and a rapid heart rate. In individuals with G6PDD, hemolytic anemia is most often triggered by bacterial or viral infections or by certain drugs (such as some antibiotics, aspirin, quinine and other antimalarials derived from quinine). Hemolytic anemia can also occur after inhaling fava plant pollen or consuming fava beans (a reaction called favism). In newborns, G6PDD is also a significant cause of mild to severe jaundice. Many people with G6PDD, however, are asymptomatic.

Glucose-6-phosphate Dehydrogenase Deficiency References

Pentose Phosphate Pathway References