G6PD deficiency.

T HIRTY-FIVE YEARS ago Dr William Dameshek, the first editor of the emerging journal Blood, invited me to write a review on “The Hemolytic Effect of Primaquine.”’ At the time, primaquine sensitivity, which had just recently been shown to be caused by a deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD); represented a unique example of an inherited deficiency of an enzyme that caused hemolytic anemia. Although many other red blood cell (RBC) enzyme deficiencies are now k n ~ w n , ~ “ G6PD deficiency still reigns as the most common of all clinically significant enzyme defects, not only in hematology, but in human biology as a whole. A variety of drugs and infections cause hemolytic anemia in persons with the deficiency, and nonhematologic sequelae have been claimed as well. Using classical biochemical techniques, enormous apparent diversity of mutations causing G6PD deficiency was documented in hundreds of publications. The distribution of the deficiency in different populations has been investigated exhaustively, and gene frequencies of over 0.5 have been observed in some ethnic groups. With the advances made possible by the cloning of G6PD cDNA and gene7.* has come a better understanding of the diversity that exists. In this review, I will attempt to put what we have learned in the past 35 years into perspective and to touch upon what still needs to be learned.