Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is a hereditary, sex-linked enzyme defect. It results in the breakdown of red blood cells when the person is exposed to certain drugs or the stress of infection .

The primary effect of G-6-PD deficiency is the reduction of the enzyme G-6-PD in red blood cells, causing destruction of the cells (hemolysis). Ultimately, this hemolysis leads to anemia -- either acute or chronic.

In the United States, many more black than white people have the disorder. Approximately 10-14% of the black male population is affected. The disorder may occasionally affect a black women to a mild degree (depending on their genetic inheritance).

The disease also tends to affect people of Middle Eastern decent, particularly Kurdish and those of Sephardic Jewish descent.

People with the disorder are not normally anemic. They do not display any evidence of the disease until the red blood cells are exposed to certain chemicals in food or medicine, or to stress.

Medications that can bring on this reaction include:

• Antimalarial drugs
• Aspirin
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Quinidine
• Quinine
• Sulfonamides (antibiotic)Nitrofurantoin

The chronic anemia is unaffected by exposure to these drugs.

Other chemicals, such as those in mothballs, can also bring about hemolysis in people with G-6-PD deficiency. The risk of acute hemolytic crisis can be decreased by reviewing the family history for any evidence of hemolytic anemias or spherocytosis, or testing before giving any medications belonging to the above classes.

The hemolysis episodes are usually brief, because newly produced (young) red blood cells have normal G6PD activity.

Risk factors for G-6-PD deficiency are being black, being male, or having a family history of G6PD deficiency. Another type of this disorder can occur in whites of Mediterranean descent. This form is also associated with acute episodes of hemolysis. Episodes are longer and more severe than in the other types of the disorder.

• Dark urine
• Enlarged spleen
• Fatigue
• Paleness
• Rapid heart rate
• Shortness of breath
• Yellow skin color (jaundice)

• Anemia
• Hemolysis
• Increase in the number of young red blood cells in circulation, following a hemolytic crisis
• Reduced G-6-PD activity

Tests may find:

• Elevated absolute reticulocyte count
• Elevated bilirubin levels
• Elevated serum LDH
• Heinz bodies present on examination of the peripheral blood smear using special stains
• Hemoglobin in the urine
• Low red blood cell count and hemoglobin levels
• Low serum haptoglobin

Additional tests may include:

• Methemoglobin reduction test
• Methylene blue test

If the cause of a hemolytic crisis is an infection, it should be treated. If the cause is a drug, the drug should be stopped. People with the Mediterranean form, or those in hemolytic crisis, may occasionally require transfusions.

Spontaneous recovery from hemolytic crises is the usual outcome.

Rarely, kidney failure or death may occur following a severe hemolytic event.

Call for an appointment with your health care provider if symptoms of hemolytic anemia due to G-6-PD deficiency develop.

Call your health care provider if you have G-6-PD deficiency and symptoms of hemolytic anemia do not disappear after treatment of the cause.

People with G-6-PD must strictly avoid anything that can bring on an episode, especially drugs known to cause oxidative reactions. Talk to your health care provider about medications in this class.

Genetic counseling or genetic information may be of interest to carrier women and affected men.

Hoffman R, Benz Jr. EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, Pa: Churchill Livingston; 2005:658-60.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders; 2004:1027-28.