Primaquine Sensitivity:  Glucose-6-Phosphate Dehydrogenase Deficiency: An Inborn Error of Metabolism of Medical and Biological Significance

The potential danger of hemolysis from use of the 8-aminoquinoline antimalarial drug, pamaquine (Plasmoquine), has been known since 1926.¹ Earle,² in 1948, reported that pamaquine caused hemolysis in 5%-10% of American Negroes, but rarely in Caucasians. Similar observations were made in 1952 by Hockwald³ during an evaluation of the related, but less toxic drug, primaquine; it was further noted that the severity of hemolysis was determined by the amount of drug administered. In 1954, Dern⁴ discovered that the susceptibility to hemolysis by primaquine is due to an intrinsic abnormality of the erythrocyte. Dern, Beutler, and Alving⁵ reported that the hemolysis is self-limited in that clinical recovery occurs even if the daily dose of drug is continued. Many drugs can precipitate hemolysis.⁶ This hypersusceptibility to hemolysis by drugs is a genetically transmitted inborn error of metabolism.⁷ The first biochemical abnormality to characterize drug-sensitive cells,