Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that supports the function and survival of red blood cells as they transport oxygen throughout the body. The enzyme protects red blood cells from harmful substances that can build up during an infection or as a side effect of certain medications. G6PD deficiency is an inherited genetic condition where the body does not produce enough of this enzyme. This lack of protection makes red blood cells vulnerable to destruction, a process called hemolysis. A G6PD assay is a blood test that measures the level of G6PD enzyme activity to determine if a deficiency is present.
Reasons for G6PD Assay Testing
A primary reason for performing a G6PD assay is the investigation of unexplained hemolytic anemia, where red blood cells are destroyed faster than the body can produce them. Symptoms that might prompt a physician to order the test include significant fatigue, pale skin, a rapid heartbeat, shortness of breath, and jaundice, a yellowing of the skin and eyes. The appearance of dark, reddish-brown urine is another sign, indicating hemoglobin from broken-down red blood cells.
The test is frequently ordered after a patient experiences a hemolytic episode following exposure to a known trigger. Testing may also be performed before prescribing certain high-risk drugs, especially in populations where G6PD deficiency is more common.
Another reason for testing is a family history of the disorder. Since G6PD deficiency is an X-linked inherited condition, it is more common in males and has a higher prevalence in individuals of African, Asian, or Mediterranean descent. In some regions, newborn screening programs include G6PD testing to identify the deficiency early, particularly if a baby develops severe neonatal jaundice.
The G6PD Assay Test Procedure
The G6PD assay is performed on a blood sample. For adults and older children, a healthcare professional draws blood from a vein in the arm, a process known as venipuncture. For newborns, the sample is often obtained through a heel prick.
The collected blood sample is sent to a laboratory for analysis of G6PD enzyme activity within the red blood cells. A quantitative test is the most precise method, measuring the exact amount of enzyme activity and reporting it as a specific value (U/gHb). This provides a clear picture of the degree of any deficiency.
A qualitative test, such as the fluorescent spot test, offers a more general result, determining if G6PD activity is normal or low without a precise measurement. This screening test is often used for large-scale screening because it is faster and less expensive. No special preparation is required before a G6PD assay unless specifically instructed by a doctor.
Interpreting G6PD Assay Results
The interpretation of G6PD assay results depends on the level of enzyme activity measured in the red blood cells compared to established normal ranges. For individuals over one year of age, a normal range is 8.8 to 13.4 units per gram of hemoglobin (U/gHb). Results falling within this range indicate that the G6PD enzyme is functioning as expected.
A result showing G6PD activity below the normal range confirms a diagnosis of G6PD deficiency. The degree of deficiency can vary, which often correlates with the severity of potential symptoms. Intermediate levels of enzyme activity can be observed in females who are carriers of the genetic trait due to a process called skewed X-inactivation.
It is important to time the test correctly, as G6PD levels can be falsely normal during or immediately after a hemolytic episode. This occurs because the oldest red blood cells, with the lowest G6PD levels, are destroyed first. The remaining younger red blood cells have higher enzyme activity, which can skew the results, so a doctor may repeat the test weeks after an event has resolved.
A deficient result indicates an increased vulnerability of red blood cells to oxidative stress. This stress is caused by an accumulation of certain reactive chemical byproducts. Triggers that increase this stress can lead to the rapid destruction of red blood cells, known as acute hemolytic anemia.
Management Following a G6PD Deficiency Diagnosis
Once a diagnosis of G6PD deficiency is confirmed, management focuses on patient education and prevention. The primary strategy is the strict avoidance of known triggers that can induce a hemolytic episode by learning which medications, foods, and chemicals pose a risk.
Key preventative measures include:
- Informing all healthcare providers, including doctors and pharmacists, of their G6PD status.
- Avoiding specific medications, such as certain antibiotics (including sulfonamides) and antimalarials.
- Not eating fava beans, as this can cause a severe hemolytic reaction known as favism.
- Avoiding exposure to naphthalene, a chemical commonly found in mothballs.
Genetic counseling may be recommended for individuals planning to have children to discuss the inheritance pattern. While there is no cure for G6PD deficiency, most individuals can lead a normal life by carefully avoiding triggers. In the event a hemolytic episode does occur, medical care is supportive, though severe anemia may require a blood transfusion.