Case Study 1: G6PD

David Grkovicious

Andrew Wattals

Tim Cryal

What is G6PD?

• Stands for Glucose 6 phosphate dehydrogenase

• Gene Map Locus: Xq28

What causes deficiency?

• What is causing G6PD deficiency on the molecular level?" Most individuals with G6PD deficiency have a qualitative abnormality in the structure of the G6PD enzyme (Scriver et al., 1995)

Why does deficiency lead to hemolytic anemia?

• glucose-6-Phosphate Dehydrogenase(G6PD) deficiency is the most common human enzyme deficiency; an estimated 400 million people worldwide are affected by this enzymopathy (Scriver etal., 1995).

Why does deficiency lead to hemolytic anemia?

• An anemic response can be induced in affected individuals by certain oxidative drugs, fava beans, or infections (Beutler, 1994).

Hexose monophosephate

• The main metabolic pathway in activated neutrophils, rendering them relatively insensitive to inhibitors of oxidative phosphorylation. Congenital deficiency of the first enzyme in the shunt, glucose-6-phosphate dehydrogenase, produces a sensitivity to infection similar to that seen in chronic granulomatous disease.

Testing the population!

• Screening is done with a blood test

• This is cheap easy and reliable

• University of fla pays you 20 for the test

• If you are positive you get 2350 for volentering for reasearch.

Interestingly

• G6PD deficient individuals are prohibited from taking certain drugs...The common theme shared among all of these drugs is that they are oxidizing agents.In G6PD deficient individuals, oxidative stress may result in the denaturation, or unfolding, of the hemoglobin molecule, the principal oxygen carrying molecule inside the red blood cell

Sex-Linked!

• In males, however, where there is only one X-chromosome, one defective G6PD gene is sufficient to cause G6PD deficiency.

Who else susceptible?

• African Americans and some isolated tribes in Africa and Southeast Asia exhibit the highest frequency of incidence for any given population; a defective enzyme can be found in as many as one in four people among these populations (Scriver et al., 1995).