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Glucose-6-phosphate dehydrogenase (G6PD) deficiency                               See  G6PD brochure

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.

Classification:
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.

Laboratory results:
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 infection.
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

Sulfisoxazole (Gantrisin)                             Primaquine §
Trimethoprim-sulfamethoxazol (Septra)    Pamaquine *
Salicylazosulfapyridine (Azulfidine,
sulfasalazine)                                             Anthelmintics
Sulfanilamide                                              beta- Naphthol
Sulfapyridine                                              Stibophen
Sulfadimidine                                             Niridazole

Sulfacetamide (albucid)                             Analgesics
Diaminodiphenylsulfone (dapsone)              Acetylsalicylic acid (aspirin)
Sulfoxone                                              Acetophenetidin (phenacetin)

Glucosulfone sodium (Promin)                     Miscellaneous
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)
Nalidixic acid            
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

OTHER ANTIBACTERIALS

ANTIMALARIALS

ANTHELMINTICS

ANALGESICS ¶

MISCELLANEOUS

Adapted from WHO Working Group: Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989;67:601–611.

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.

Ref:
Washington Manual of Medical Therapeutics, 29th ed., 1998
Goldman: Cecil Textbook of Medicine, 21st Ed.,  2000

       

2007