To determine whether you have an inherited G6PD deficiency
A blood sample drawn from a vein in your arm, by fingerstick, or by heelstick (newborns)
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme involved in energy production. It is found in all cells, including red blood cells (RBCs) and helps protect them from certain toxic by-products of cellular metabolism. A deficiency in G6PD causes RBCs to become more vulnerable to breaking apart (hemolysis) under certain conditions. This test measures the amount of G6PD in RBCs to help diagnose a deficiency.
G6PD deficiency is a genetic disorder. When individuals who have inherited this condition are exposed to a trigger such as stress, an infection, certain drugs or other substance(s), significant changes occur in the structure of the outer layer (cell membrane) of their red blood cells. Hemoglobin, the life-sustaining, oxygen-transporting protein within RBCs, forms deposits (precipitates) called Heinz bodies. Some individuals may experience these reactions when exposed to fava beans, a condition called "favism." With these changes, RBCs can break apart more readily, causing a decrease in the number of RBCs. When the body cannot produce sufficient RBCs to replace those destroyed, hemolytic anemia results and the individual may develop jaundice, weakness, fatigue, and/or shortness of breath.
G6PD deficiency is the most common enzyme deficiency in the world, affecting more than 400 million people. It may be seen in up to 10% of African-American males and 20% of African males. It is also commonly found in people from the Mediterranean and Southeast Asia.
G6PD deficiency is inherited, passed from parent to child, due to mutations or changes in the G6PD gene that cause decreased enzyme activity. There are over 440 variants of G6PD deficiency. The G6PD gene is located on the sex-linked X chromosome. Since men have one X and one Y sex chromosome, their single X chromosome carries the G6PD gene. This may result in a G6PD deficiency if a male inherits the single X chromosome with an altered gene.
Since women have two X sex chromosomes, they inherit two copies of the G6PD gene. Women with only one mutated gene (heterozygous) produce enough G6PD that they usually do not experience any symptoms (i.e., asymptomatic), but under situations of stress, they may demonstrate a mild form of the deficiency. In addition, a mother may pass the single mutated gene to any male children. Rarely do women have two mutated gene copies (homozygous), which could result in G6PD deficiency.
G6PD deficiency is a common cause of persistent jaundice in newborns. If left untreated, this can lead to significant brain damage and mental retardation.
Most people with G6PD deficiency can lead fairly normal lives, but there is no specific treatment apart from prevention. They must be cautious and avoid certain medications such as aspirin, phenazopyridine and rasburicase, antibiotics with "sulf" in the name and dapsone, anti-malarial drugs with "quine" in the name, foods such as fava beans, and chemical substances such as naphthalene (found in moth balls). Note that fava beans, often called broad beans, are commonly grown in the Mediterranean area. Acute viral and bacterial infections can also initiate episodes of hemolytic anemia as well as elevated levels of acid in the blood (i.e., acidosis). Individuals should consult with their healthcare practitioner to get a comprehensive list of these triggers. A good starting point is the list found on the G6PD Deficiency Favism Association website.
With hemolytic anemia, RBCs are destroyed at an accelerated rate and the person affected becomes pale and fatigued (anemic) as their capacity for providing oxygen to their body decreases. In severe cases of RBC destruction, jaundice can also be present. Most of these episodes are self-limiting, but if a large number of RBCs are destroyed and the body cannot replace them fast enough, then the affected person may require a blood transfusion. This condition can be fatal if not treated. A small percentage of those affected with G6PD deficiency may experience chronic anemia.
How is it used?
Glucose-6-phosphate dehydrogenase (G6PD) enzyme testing is used to screen for and help diagnose G6PD deficiencies. It may be used to screen children who had unexplained persistent jaundice as a newborn. Currently, newborns are not routinely screened for G6PD deficiency; however, this is dependent upon the specific state that provides the testing. According to the National Newborn Screening and Genetics Resource Center, as of November 2014, two states provide G6PD testing as part of their newborn screening panel: Pennsylvania and the District of Columbia.
G6PD testing may also be used to help establish a diagnosis for people of any age who have had unexplained episodes of hemolytic anemia, jaundice, or dark urine. If the person had a recent viral or bacterial illness or was exposed to a known trigger (such as fava beans, a "sulfa" drug, or naphthalene), followed by a hemolytic episode, then G6PD deficiency may be considered.
Repeat G6PD testing may occasionally be ordered to confirm initial findings. Screening tests typically involve a simple qualitative test that only tells if the person has a certain high level of G6PD in his or her cells. Confirmation testing will involve a quantitative test, with which the actual amount of enzyme activity is measured.
In the most common form of G6PD deficiency seen in persons of African ancestry, G6PD levels are normal in newly produced cells but decrease up to 75% as the RBCs age. Because of this, testing is not recommended until several weeks after a hemolytic episode resolves. During the episode, a higher percentage of the older, more fragile G6PD-deficient RBCs are typically destroyed, leaving the newer, less deficient cells to be tested, potentially masking a G6PD deficiency.
Genetic testing is not routinely done but can be ordered as follow up to an enzyme test(s) that indicates a deficiency to determine which G6PD mutation(s) are present. At this time, more than 440 G6PD gene variations have been identified and can cause deficiencies of varying severity depending on the mutation(s) and on the individual person. Some mutations do not change the G6PD enzyme activity. The World Health Organization has classified the G6PD mutations into five groups based on the enzyme levels and their impact on the affected person’s health. However, only the most common G6PD mutations are identified during testing. If a specific mutation is known to be present in a family line, tests to detect that particular mutation can also be conducted. Several facilities that offer this unique testing are provided on the site Genetic Testing Registry.
When is it ordered?
G6PD enzyme testing is primarily performed when an individual has signs and symptoms associated with hemolytic anemia. Testing may be done when someone has had an episode of increased RBC destruction but after the crisis has resolved. Some signs and symptoms include:
- Fatigue, weakness
- Pale skin (pallor)
- Shortness of breath
- A rapid heart rate
- Red or brown urine (from the presence of blood/hemoglobin)
- Enlarged spleen
Testing may also be done when other laboratory test results are consistent with a hemolytic anemia. These may show increased bilirubin concentrations (bulirubinemia), hemoglobin in the urine (hemoglobinuria), decreased RBC count and haptoglobin levels, increased reticulocyte count and lactate dehydrogenase levels, presence of bite cells on a blood smear, and sometimes the presence of Heinz bodies inside the RBCs on a specially stained blood smear.
If available, screening may be performed on a newborn in the first day or two after birth.
What does the test result mean?
A low level of G6PD enzyme indicates a deficiency. An affected person is more likely to experience symptoms when exposed to a trigger. The results, however, cannot be used to predict how an affected person will react in a given set of circumstances. The severity of symptoms will vary from person to person and from episode to episode.
A normal G6PD enzyme level in a male indicates that it is unlikely he has a deficiency, and if anemia is present, it is likely due to another cause. However, if the test was performed during an episode of hemolytic anemia, it should be repeated several weeks later when the RBC population has had time to replenish and mature.
Women who are carriers, having one mutated and one normal gene copy (heterozygous), will have some RBCs that are G6PD-deficient and some that are not. These women will usually have normal or near normal G6PD levels and rarely experience symptoms. A carrier will have a normal or low normal G6PD level, thus may not be identified through G6PD screening but would be detected in a G6PD confirmation test that quantitates the overall amount of enzyme present in the cells. Note that rare female who has two mutated gene copies (homozygous) will likely show a significant decrease in G6PD level.
Why is the detection of G6PD deficiency important?
The detection allows people to work with their healthcare practitioner and to educate themselves about a condition that will affect them to some degree for their entire lives. It also allows people to talk to the healthcare practitioner about how this trait is inherited and the potential impact it may have on their children. By knowing about the deficiency and avoiding potential triggering substances and situations, most of those who have G6PD deficiencies can lead relatively normal lives.
Are there ways to test for G6PD deficiency other than enzyme testing?
Yes, genetic G6PD testing may sometimes be done within a family to help identify the relevant mutation in women who are carriers (such as the mother of an affected son or daughter of an affected father) when one or more male family members have a G6PD deficiency. If a G6PD genetic mutation is detected, the person will likely have some degree of G6PD deficiency and may experience symptoms that range from nonexistent to acute and severe to chronic at various times throughout the person's life. An affected man will pass the mutation on to his daughter, who will be a carrier. A heterozygous/carrier woman has a 50% chance of passing it on to each of her children. A homozygous woman with two mutated X chromosomes will pass one of her mutations to all of her children. The mutation(s) will be the same within the family and may be common in a geographic region. [For more information on genetic testing, see The Universe of Genetic Testing].
Is it important to determine which mutation I have?
Not for you personally, but it may aid in detecting the mutation in other family members. Genetic testing usually only tests for the most common mutations. If you have a specific mutation, then testing other family members for that mutation is useful in establishing familial patterns.
Do I need to tell a new healthcare provider that I have a G6PD deficiency if I do not have any symptoms?
Yes, this is an important part of your medical history and will affect future medical procedures and treatment options. Your healthcare practitioner needs to know if you have a G6PD deficiency or if you know that you are an asymptomatic carrier. A variety of medications can worsen a hemolytic episode, requiring immediate attention that could include a blood transfusion.
Is there anything else I should know?
While G6PD deficiency is found throughout the world, it is most common in those of African, Mediterranean, and Southeast Asian descent. Its geographical area of increased prevalence mirrors that of malaria. Many researchers think that G6PD deficiency may have offered a survival advantage to those infected with malaria, a parasite that infects the red blood cells (RBCs). Generally, the G6PD deficiencies associated with the Mediterranean region are the most dangerous.
Certain laboratory methods, biochemical testing, and electrophoresis can be used to distinguish between different G6PD enzyme variants. This has been used in the past to study the prevalence and levels of different types of the enzymes, both normal and deficient, but this testing is used almost exclusively in the research setting.
G6PD testing should not be done soon after a blood transfusion as the donor RBCs can mask a G6PD deficiency.