To see whether you have an inherited deficiency of Glucose-6-Phosphate Dehydrogenase (G6PD), necessary to keep red blood cells healthy
If a child has long term jaundice as a newborn and no other cause can be identified; when you have had one or more bouts of haemolysis (break-up of red blood cells, which may cause jaundice, dark urine or anaemia), particularly if the haemolysis follows "oxidative" stress caused by some medicines, foods, or infections
A blood sample taken from a vein in your arm
This test measures the amount of 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 solid lumps of haemoglobin inside the cells (Heinz Bodies), causing the red cells to break up (”haemolyse”).
G6PD deficiency (one of the most severe forms is called Favism – people with this variant are at risk if they eat broad - “fava” - beans) is the most common enzyme deficiency in the world, affecting about 400 million people. It may be seen in up to 20% of the population in Africa, 4-30% in the Mediterranean, and in Southeast Asians. Mutations or changes in the G6PD gene may lead to the production of a G6PD enzyme that has reduced performance or stability. This is expressed as decreased enzyme activity levels.
So far, more than 440 G6PD gene variations have been found and can cause enzyme activity deficiencies of varying severity depending on the particular 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. 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 long term and unexplained 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 and other triggers, including
- Aspirin (may be tolerated, depending on which type of G6PD abnormality is present)
o Chloramphenicol, Dapsone, Nitrofurantoin, Quinolones (e.g. ciprofloxacin), Sulphonamides (e.g. co-trimoxazole or Septrin)
- Antidiabetic medication
- Anti-gout medications
o Quinine, Chloroquine, Pamaquine, Primaquine
o Doxorubicin (“Adriamycin”)
- Methylene blue
- Sulfasalazine, mesalazine
- Vitamin K
- Certain FOODS
o Broad (“fava”) beans, Mangetout (“snow peas”)
- CHEMICAL SUBSTANCES
o naphthalene, found in moth balls
These triggers can cause oxidative stress resulting in a haemolytic crisis. 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 the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
G6PD testing may be requested on children who experienced persistent jaundice as a newborn that cannot be explained by another cause. It may also be requested 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 broad beans, a “sulfa” drug, or naphthalene), followed by a haemolytic episode, then G6PD deficiency may be considered. Repeat G6PD testing may occasionally be used 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 are 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. 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 normally performed on patients who have had symptoms of anaemia (such as tiredness, pallor (pale skin), a rapid heart rate) and/or jaundice. Their laboratory test results may show increased bilirubin concentrations (bulirubinemia), a decreased RBC count, an increased reticulocyte count, and sometimes the presence of Heinz bodies inside the RBCs. In severe cases there may be haemoglobin in the urine (haemoglobinuria).
G6PD activity testing is used on patients in whom other causes of the anaemia and jaundice have been ruled out and is used once the short-term acute incident has gone away. 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 appears normal, it should be repeated at a later time to confirm the G6PD level.
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 test result mean?
If there is a decreased G6PD level, then it is the more likely that the patient will 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. They will usually have normal or near normal G6PD levels and few will experience symptoms. A carrier may not be detected through G6PD screening; however, the rare homozygous female will show a significant decrease in G6PD level.
If a G6PD genetic mutation is detected, the patient is likely to have some degree of G6PD deficiency. An individual patient may experience symptoms that range from nonexistent to severe at various times throughout their life.
Assuming the other parent has normal G6PD genes:
- An affected male’s daughters will all be carriers
- An affected male’s sons will all have normal G6PD genes
- A heterozygous/carrier female has a 50% chance of passing it on to each of her children – affected sons will have G6PD deficiency, affected daughters carriers.
- Rare homozygous females (with both G6PD genes abnormal) will have affected sons and carrier daughters.
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 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 South East Asia. The geographical area where G6PD deficiency is seen is similar to 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.
Why is the detection of G6PD deficiency important?
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.
Is it important to find out which mutation I have?
Not for you personally, but it may help 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.
Do I need to tell a new doctor 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 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 cause or make a haemolytic episode worse, requiring immediate attention including a blood transfusion.
Elsewhere On The Web
March of Dimes: Newborn Screening Tests
National Newborn Screening and Genetics Resource Center
An Introduction to G6PD Deficiency
Netdoctor.co.uk: Oxidative Stress
G6PD Deficiency:Favism Association