TOC | HEME
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is by far the most common hereditary RBC enzyme defect associated with hereditary hemolytic anemia, affects millions of individuals from all races around the world, and hundreds of G6PD variants have been described. It is a sex-linked disorder (the G6PD gene is located on the X chromosome) that typically affects men. The enzyme deficiency results in RBCs that are more susceptible to oxidant stress than are normal RBCs, leading to chronic or episodic hemolysis.
The prevalence of G6PD deficiency in African black, Mediterranean, Indian, and Southeast Asian populations is thought to derive from the relative protection afforded G6PD heterozygotes against Plasmodium falciparum malaria.
A mild form of the deficiency occurs in perhaps 10% of black men and is characterized by hemolytic episodes triggered by infections or drug exposure. A more severe enzyme deficiency, such as the Mediterranean variety, results in hemolysis when susceptible individuals are exposed to fava beans. The most severe type causes a chronic hereditary nonspherocytic hemolytic anemia in the absence of an inciting cause.
The peripheral smear shows "bite cells"; RBC inclusions (Heinz bodies) are seen with special stains. Measurement of enzyme levels usually establish the diagnosis. However, senescent RBCs contain less G6PD and are destroyed more easily than are younger cells, so that after a hemolytic episode, the G6PD level may be normal, reflecting the younger population of cells in the circulation.
Hemoglobin electrophoresis test may show deficiency of the G6PDH.
Hemolysis in the setting of G6PD deficiency is most often caused by acute
Oxidant drugs represent the other major category of oxidant stress that can lead to acute and/or chronic hemolysis (Table below ) .
DRUGS THAT COMMONLY CAUSE HEMOLYSIS IN G6PD DEFICIENCY
Sulfonamides and Sulfones Antimalarials
Trimethoprim-sulfamethoxazol (Septra) Pamaquine *
Sulfanilamide beta- Naphthol
Diaminodiphenylsulfone (dapsone) Acetylsalicylic acid (aspirin)
Sulfoxone Acetophenetidin (phenacetin)
Glucosulfone sodium (Promin)
Other Antibacterials Probenecid
Nitrofurans Vitamin K analogues (1 mg menaphthone)
Nitrofurantoin (Furadantin) Dimercaprol (BAL)
Nitrofurazone (Furacin) Mepacrine (quinacrine HCl)
Furazolidone Methylene blue
Chloramphenicol Toluidine blue
p -Aminosalicylic acid Naphthalene (mothballs)
Adapted from WHO Working Group: Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 67:601, 1989.
Table -- DRUGS THAT COMMONLY CAUSE HEMOLYSIS IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY *
SULFONAMIDES AND SULFONES
Adapted from WHO Working Group: Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989;67:601611.
TREATMENT AND PROGNOSIS
Treatment consists of adequate hydration to protect renal function during hemolysis, avoidance of precipitating factors and, if necessary, RBC transfusion.
Because all but a few rare individuals with G6PD deficiency are hematologically normal in the absence of an exogenous oxidant stress, no treatment is required for the deficiency itself. Mild to moderate episodes of acute hemolysis can often be managed by removal of the offending drug or by treatment of the concurrent infection. Severe hemolytic episodes in individuals with GdMed and other unstable G6PD variants may require red cell transfusions to alleviate the signs and symptoms of acute anemia, as well as measures designed to protect against the potential renal complications of hemoglobinuria.
Washington Manual of Medical Therapeutics, 29th ed., 1998
Goldman: Cecil Textbook of Medicine, 21st Ed., 2000