Screening For G6PD Deficiency Presentation to AFEB May 2003

1. Screening For G6PD DeficiencyPresentation to AFEB May 2003 COL G. Dennis Shanks Tony Philip MPH MAJ Anthony Littrell I want to speak to the Board today about Glucose 6 Phosphate Dehydrogenase Deficiency and its impact on the use of the antimalarial drug primaquine. The Board last reviewed this topic in 1998.I want to speak to the Board today about Glucose 6 Phosphate Dehydrogenase Deficiency and its impact on the use of the antimalarial drug primaquine. The Board last reviewed this topic in 1998.

2. Background on G6PD G6PD is an enzyme in the pentose phosphate pathway Converts NADP+ to NADPH G6PD deficiency is a sex-linked genetic disorders, with full expression in males Persons who are G6PD deficient are at increased risk for experiencing hemolytic anemia when taking primaquine G6PD is an enzyme which is part of the biochemical pathway that produces hydrogen molecules for reduction equivalents in biosynthesis. G6PD is a gene that falls on the X chromosome and thus is sex linked with full expression in males. G6PD gene has been extensively selected over the past 10,000 years apparently for its survival advantage during malaria infection. The practical problem for people with a deficiency in G6PD is that they can have hemolytic anemia when exposed to a variety of drugs. The exact mechanism with oxidizing agents is clear, but that is not true with primaquine which also initiates hemolytic anemia in G6PD persons. G6PD is an enzyme which is part of the biochemical pathway that produces hydrogen molecules for reduction equivalents in biosynthesis. G6PD is a gene that falls on the X chromosome and thus is sex linked with full expression in males. G6PD gene has been extensively selected over the past 10,000 years apparently for its survival advantage during malaria infection. The practical problem for people with a deficiency in G6PD is that they can have hemolytic anemia when exposed to a variety of drugs. The exact mechanism with oxidizing agents is clear, but that is not true with primaquine which also initiates hemolytic anemia in G6PD persons.

3. G6PD Genetic Variants Two most important for U.S. Army (out of 400): (A - ) Variant affects approximately 10% of African Americans enzyme usually >10% normal (B - ) Variant (MED) is the most common type affecting people from Eastern Mediterranean Enzyme usually <10% of normal -There are many G6PD variants which have been studied genetically. Two groups are of importance for this discussion A minus is the most common form of G6PD deficiency and is primarily found in persons of African descent. It is a relatively mild deficiency with most persons having >10% activity of the normal enzyme. B minus gene is primarily found in people of Mediterranean descent such as Greeks, Italians, Turks, Libyans, Moroccans etc. It is a more severe deficiency with a much higher likelihood of severe hemolysis if exposed to an initiating agent.-There are many G6PD variants which have been studied genetically. Two groups are of importance for this discussion A minus is the most common form of G6PD deficiency and is primarily found in persons of African descent. It is a relatively mild deficiency with most persons having >10% activity of the normal enzyme. B minus gene is primarily found in people of Mediterranean descent such as Greeks, Italians, Turks, Libyans, Moroccans etc. It is a more severe deficiency with a much higher likelihood of severe hemolysis if exposed to an initiating agent.

4. Geographic Distribution of G6PD Variants