GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

Essentials of Diagnosis

X-linked recessive disorder seen commonly in American black men.

Episodic hemolysis in response to oxidant drugs or infection.

Minimally abnormal peripheral blood smear.

Reduced levels of glucose-6-phosphate dehydrogenase between hemolytic episodes.
General Considerations
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a hereditary enzyme defect that causes episodic hemolytic anemia because of the decreased ability of red blood cells to deal with oxidative stresses. Oxidized hemoglobin denatures and forms precipitants called Heinz bodies. These Heinz bodies cause membrane damage, which leads to removal of these cells by the spleen.
Numerous types of G6PD enzymes have been described. The normal type found in whites is designated G6PD-B. Most American blacks have G6PD-A, which is normal in function. Ten to 15 percent of American blacks have the variant G6PD designated A–, in which there is only 15% of normal enzyme activity, and enzyme activity declines rapidly as the red blood cell ages past 40 days, a fact that explains many of the clinical findings in this disorder. Many other G6PD variants have been described, including some Mediterranean variants with extremely low enzyme activity.
Clinical Findings
G6PD deficiency is an X-linked recessive disorder affecting 10–15% of American black males. Female carriers are rarely affected—only when an unusually high percentage of cells producing the normal enzyme is inactivated.
SYMPTOMS AND SIGNS
Patients are usually healthy, without chronic hemolytic anemia or splenomegaly. Hemolysis occurs as a result of oxidative stress on the red blood cells, generated either by infection or exposure to certain drugs. Common drugs initiating hemolysis include dapsone, primaquine, quinidine, quinine, sulfonamides, and nitrofurantoin. Even with continuous use of the offending drug, the hemolytic episode is self-limited because older red blood cells (with low enzyme activity) are removed and replaced with a population of young red blood cells with adequate functional levels of G6PD. Severe G6PD deficiency (as in Mediterranean variants) may produce a chronic hemolytic anemia.
LABORATORY FINDINGS
Between hemolytic episodes, the blood is normal. During episodes of hemolysis, there is reticulocytosis and increased serum indirect bilirubin. The red blood cell smear is not diagnostic but may reveal a small number of "bite" cells—cells that appear to have had a bite taken out of their periphery (see blood smear). This indicates pitting of hemoglobin aggregates by the spleen. Heinz bodies may be demonstrated by staining a peripheral blood smear with cresyl violet (see blood smear); they are not visible on the usual Wright-stained blood smear. Specific enzyme assays for G6PD may reveal a low level but may be misleading if they are performed shortly after a hemolytic episode when the enzyme-deficient cohort of cells has been removed. In these cases, the enzyme assays should be repeated weeks after hemolysis has resolved. In severe cases of G6PD deficiency, enzyme levels are always low.

Fig.

Glucose-6-phosphate dehydrogenase deficiency. (Peripheral blood smear, 100 x.) Several features of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the setting of an oxidative challenge are shown. The polychromatophils (large, bluish young red blood cells) and nucleated red blood cells indicate the current hemolytic state. Also shown are "bite" cells, which are red blood cell morphologic changes that are the consequence of macrophage action on the Heinz bodies, which have precipitated in the inner leaflet of the red blood cell membranes. (Courtesy of L Damon.)

Fig.

Heinz bodies. (Peripheral blood, 100 x.) Brilliant cresyl blue stain. Areas of precipitated hemoglobin are seen on the inner leaflet of the red blood cell membrane. These precipitations are called Heinz bodies and are the consequence of hemoglobin oxidation and denaturation. Severe oxidative stress can result in abnormal red blood cell membrane deformability and subsequent extravascular hemolysis. (Courtesy of L Damon.)

Treatment
No treatment is necessary except to avoid known oxidant drugs.

Mehta A et al. Glucose-6-phosphate dehydrogenase deficiency. Baillieres Best Pract Res Clin Haematol. 2000 Mar;13(1):21–38. [PMID: 10916676]