What is being tested?
This test measures the amount of glucose-6-phosphate dehydrogenase (G6PD) in the red blood cells (RBCs). G6PD is an enzyme that protects red blood cells from the effects of oxidation. If there is insufficient G6PD, the RBCs become more vulnerable to oxidative damage. If these RBCs are exposed to an oxidative agent (for a list, click here), it changes their cellular structure, precipitating haemoglobin inside the cells (Heinz bodies), causing them to break apart (haemolysis).
G6PD deficiency (most severe form is called Favism) is the most common enzyme deficiency in the world, affecting about 400 million people according to the Nemours Foundation. It may be seen in up to 20% of the population in Africa, 4-30% in the Mediterranean and is found in Southeast Asia. Mutations or changes in the G6PD gene may lead to the production of a G6PD enzyme that has diminished functionality or stability. This is expressed as decreased enzyme activity levels.
So far, more than 440 G6PD gene variations have been identified and can cause enzyme activity deficiencies of varying severity depending on the mutation and on the individual person. The G6PD gene is located on the X chromosome. Since males have one X and one Y chromosomes, a single X chromosome carrying the faulty G6PD gene with no additional healthy X chromosome will result in G6PD deficiency. Males inherit the condition from their mother.
Females have two X chromosomes, thus two copies of the G6PD gene could possibly be inherited. Heterozygous females (those with only one altered gene) can produce enough normal G6PD that they usually do not experience any symptoms. However, the presence of the abnormal form may be identified if the deficiency is detected in their male children. Rarely, a female may be homozygous, having two altered G6PD genes (the same or different mutations), and thus will experience G6PD deficiency.
In newborns, G6PD deficiency may cause persistent jaundice. Left untreated, this jaundice can lead to brain damage and mental retardation.
Most people with G6PD deficiency can lead fairly normal lives, but they must be cautious to avoid certain medications (aspirin, sulphonamides, quinine, Dapsone), foods (such as fava beans), and chemical substances (such as naphthalene, found in moth balls), which can cause oxidative stress resulting in a haemolytic crisis. A comprehensive list is found on the G6PD Deficiency Favism Association website. Infections, either bacterial or viral, can also cause oxidative stress and lead to bouts of haemolytic anaemia. With haemolytic anaemia, RBCs are destroyed at an accelerated rate and the patient becomes pale and fatigued (anaemic) as their capacity for providing oxygen to their body decreases. In some cases, jaundice can also be present during episodes of haemolysis. 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 patient may require a blood transfusion or even develop kidney problems. A small percentage of those affected with G6PD may experience chronic anaemia.
How is it used?
G6PD testing may be ordered on children who experienced persistent jaundice as a newborn that could not be explained by another cause. It may also be ordered on patients of any age who have had one or more unexplained episodes of haemolytic anaemia. If the patient had a recent viral or bacterial illness or was exposed to a known trigger (such as fava beans, a 'sulpha' drug, or naphthalene), followed by a haemolytic episode, then G6PD deficiency may be considered. Repeat G6PD testing may occasionally be ordered to confirm initial findings or if results were normal following an episode of haemolysis; in the most common form seen in persons of African ancestry, the enzyme levels are normal in newly produced cells but fall as red cells age so that only the older cells were destroyed. In these patients, during a haemolytic crisis, newer red cells are preserved and the G6PD levels may appear misleadingly normal.
Newborns are not yet routinely screened for G6PD deficiency in Australia. Genetic testing is not routinely done but can be used to determine which G6PD mutation(s) are present. Only the most common G6PD mutations are identified. If a specific mutation is known to be present in a family line, tests to detect that particular mutation can also be conducted.
When is it requested?
G6PD testing is primarily performed on patients who have had signs and symptoms of haemolytic anaemia (such as fatigue, pallor, a rapid heart rate) and/or jaundice. Their laboratory test results may show increased bilirubin concentrations (bilirubinaemia), haemoglobin in the urine (haemoglobinuria), a decreased RBC count, and haptoglobin levels, an increased reticulocyte count, lactate dehydrogenase levels, presence of bite cells on a blood smear and sometimes the presence of Heinz bodies inside the RBCs.
G6PD activity testing is ordered on patients in whom other causes of the anaemia and jaundice have been ruled out and is ordered several weeks after the acute incident has been resolved. It should not be performed when a patient is having or recovering from a haemolytic episode. This is because the older, more G6PD-deficient RBCs are usually destroyed, leaving younger less deficient RBCs to be tested. This can make the activity level appear closer to normal than it actually is. If testing is done during this time period, it should be repeated at a later time to confirm the G6PD level. The two tests available for G6PD activity are called screening (qualitative) and confirmation (quantitative).
Genetic G6PD testing may sometimes be done within a family to help identify the relevant mutation in female carriers (such as the mother of an affected son or daughter of an affected father) when one or more male family member has a G6PD deficiency.
What does the result mean?
If there is decreased G6PD level, then the more likely the patient is to experience symptoms when exposed to an oxidative stress. The results, however, cannot be used to predict how an affected patient will react in a given set of circumstances. The severity of symptoms will vary from patient to patient and from episode to episode.
If a male patient has normal G6PD levels, it is likely that he does not have a deficiency. However, if the test was performed during an episode of haemolytic anaemia, it should be repeated a few weeks later when the RBC population has had time to replenish and mature.
Heterozygous females will have both G6PD-deficient and non-deficient cells (are called carriers). They will usually have normal or near normal G6PD levels and few will experience symptoms. A carrier may not be detected through G6PD screening but would be detected in a G6PD confirmation test that quantitates the overall amount of enzyme present in the cells. The rare homozygous female will show a significant decrease in G6PD level.
If a G6PD genetic mutation is detected, the patient will likely have some degree of G6PD deficiency. An individual patient may experience symptoms that range from non-existent to severe at various times throughout their life.
Is there anything else I should know?
While G6PD deficiency is found throughout the world, it is most common in those of African or Mediterranean descent and is also found in those from Southeast Asia. Its geographical area of increased prevalence mirrors that of malaria. Some researchers think that having a G6PD deficiency has historically offered a survival advantage to those infected with malaria, a parasite that physically invades the RBCs.
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.
Common questions
The detection allows patients to work with their doctor and to educate themselves about a condition that will affect them to some degree for the rest of their lives. It also allows patients to talk to the doctor 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.
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 one of the common mutations, then testing other family members for that mutation is useful in establishing familial patterns.
Yes, this is an important part of your medical history and will affect future procedures and treatment options. Your doctor needs to know if you have a G6PD deficiency or if you know that you are an asymptomatic carrier. As noted, a variety of drugs can exacerbate the haemolytic episode, requiring immediate attention including a blood transfusion.
More information
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