Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency) is a form of anemia where there is an important underlying enzyme deficiency. G6PD deficiency is an X-linked disorder and fully expressed in the male and in homozygous females. In heterozygous females it is expressed in a variable fashion.
There are more than 100 known mutants of this disorder, but clinically the most important one is a drug sensitive variety that affects approximately 10% of black males in the US and less than 10% female blacks. People of Mediterranean origin are much less affected by this disorder.
Because the older red blood cells are affected in this disorder more than the young ones, there is hemolysis of older RBC’s. Certain conditions that strain RBC’s as well like fever, viral or bacterial infections and diabetic acidosis, will lead to even more anemia by hemolysis. Certain drugs and substances can produce peroxide and cause oxidation of hemoglobin and red blood cells, which in turn can cause hemolysis. Simple drugs like ASA, sulfonamides, phenacetin, dapsone, vitamin K derivatives, and even consuming fava beans will cause hemolysis in susceptible people. Many affected people react to fentanyl, a drug that is used for anesthetic induction, with an acute hemolysis. The anesthetist has to use different drugs during surgery. There are enormous differences between people in the sense that the G6PD deficiency is expressed in different degrees of severity (dependent on gene expression). In blacks the older cell population of RBC’s is selectively targeted by hemolysis putting a limit of less than 25% of the total RBC mass that can be affected. In whites all of the RBC’s can be affected so that they tend to get a much more severe hemolysis, which can be lethal in severe cases. The degree of severity depends on the dose of the offending drug or substance and on how much peroxide is formed by this toxic process. With severe hemolysis hemoglobinuria and kidney failure can develop from the hemolytic process.
Symptoms
A patient, who is anemic and has an acute hemolytic anemia with jaundice, particularly in a black male, should be checked for G6PD deficiency. Chills, a fever and pain in the back and in the stomach may accompany the anemia.
Diagnosis
The reticulocytes are increased markedly during hemolysis. Heinz bodies occur early in the illness, but are subsequently removed by the spleen. Also cells that look like a bite was taken from the periphery (bit cells) are characteristic of G6PD deficiency. Specific enzymes assays are available to come to the accurate diagnosis.
Treatment
Treatment during a hemolysis attack is supportive. It would be rare to require a transfusion of blood. Any drug or substance that can be identified as having precipitated the bout of acute hemolysis would have to be avoided from now on. No treatment is available to fix the genetic defect.
References:
1. Merck Manual (Home edition): Anemia
2. Noble: Textbook of Primary Care Medicine, 3rd ed., Mosby Inc. 2001
3. Goldman: Cecil Medicine, 23rd ed., Saunders 2007: Chapter 162 – APPROACH TO THE ANEMIAS
