An Overview of G6PD Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world. Approximately 400 million people are affected worldwide. There is great variability in severity based on which mutation is inherited.

G6PD is an enzyme found in the red blood cells that provides energy to the cell. Without this energy, the red blood cell is destroyed by the body (hemolysis), leading to anemia and jaundice (yellowing of the skin).

Risk Factors

The most significant risk factor for G6PD is having a parent with an X-linked recessive condition. If only the mother carries the X-linked recessive disease, changes of children inheriting depending on gender. While a son has a 50% chance of being unaffected or affected, a daughter has a 50% chance of being unaffected but a 50% chance of being a carrier. Additionally, if only the father carries the gene, sons are unaffected, and daughters remain carriers.

The gene for G6PD is located on the X chromosome, making males most susceptible to G6PD deficiency (X-linked disorder). G6PD deficiency protects people from being infected with malaria, so it is more commonly seen in areas with high malaria infection rates, such as Europe, and Asia. In the United States, 10% of African-American males have G6PD deficiency.

Symptoms

Symptoms depend on which mutation you inherit. Some people may never be diagnosed, as no symptoms are present. Some patients with G6PD deficiency have symptoms only when exposed to certain medications or foods (see the list below). Some people may be diagnosed as newborns after experiencing severe jaundice (also called hyperbilirubinemia). In those patients and in those with more severe forms of G6PD deficiency with chronic hemolysis, symptoms include:

• Pallor or pale color to skin
• Fever
• Confusion
• Rapid heart rate
• Fatigue and weakness
• Feeling faint or dizzy
• Yellowing of skin (jaundice) or eyes (scleral icterus)
• Dark urine
• Heart murmur
• Enlarged liver or spleen

Diagnosis

Diagnosing G6PD deficiency can be tricky. First, your physician must suspect that you have hemolytic anemia (the breakdown of red blood cells). This is usually confirmed by a complete blood count or a and a reticulocyte count.

Reticulocytes are immature red blood cells sent from the bone marrow in response to the anemia. Anemia with elevated reticulocyte count is consistent with hemolytic anemia. Other labs might include a bilirubin count, which will be elevated. Bilirubin is released from red blood cells when they are broken down and cause jaundice during hemolytic crises.

In the process of determining the diagnosis, your physician will need to rule out autoimmune hemolytic anemia. The direct antiglobulin test (also called direct Coombs test) assesses whether there are antibodies to red blood cells causing them to be attacked by your immune system. As in most cases of hemolytic anemia, the peripheral blood smear (microscope slide of the blood) is very helpful. In G6PD deficiency, bite cells and blister cells are common. These are caused by changes that occur to the red blood cell as it is destroyed.

If G6PD deficiency is suspected, a G6PD level can be sent off. A low G6PD level is consistent with G6PD deficiency. Unfortunately, in the midst of an acute hemolytic crisis, a normal G6PD level does not rule out deficiency. The numerous reticulocytes present during the hemolytic crisis contain normal levels of G6PD, causing a false negative. If highly suspected, the testing should be repeated when a patient is at baseline status.

Treatment

Avoid medications or foods that trigger hemolytic (red blood cell breakdown) crises. Along with moth balls, which trigger symptoms G6PD deficiency, the below medications and foods should also be avoided:

• Fava beans (also called broad beans)
• Antimalarial medicines such as quinine
• Aspirin (high doses)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Quinidine
• Sulfa drugs
• Antibiotics such as quinolones, nitrofurantoin

Blood transfusions are used when the anemia is severe and the patient is symptomatic. Fortunately, most patients never need a transfusion.