G6PD Mutations Cause Favism

Fava beans are a staple food in Mediterranean diets; however, they contain
a glycoside compound called vicine, which generates free oxygen
radicals and H₂O₂ when it is metabolized in red blood cells. The enzyme
glucose-6-phosphate dehydrogenase (G6PD), which is part of the pentose
phosphate pathway and generates NADPH for cells, helps protect
cells against oxidative damage caused by compounds such as vicine. Individuals
with a genetic defect in the glucose-6-phosphate dehydrogenase
gene (G6PD) get sick from eating fava beans because these individuals
are unable to produce high levels of NADPH to counteract the toxic
effects of vicine in red blood cells. This diet-induced physiologic condition
is called favism, which in extreme cases can lead to hemolytic anemia
(red blood cell death). Deficiency in the glucose-6-phosphate dehydrogenase
enzyme represents the most common human genetic variant linked
to metabolic disease, with over 400 million people worldwide carrying
G6PD mutations.