G6PD
Also known as: G-6-PD
Name: Glucose-6-phosphate dehydrogenase
Related tests: Blood smear, Full blood count
Why is the test done?
To find out whether G6PD deficiency has been inherited
When to get tested?
If a newborn baby has persistent jaundice not caused by any other identified cause; if there are one or more intermittent episodes of haemolytic anaemia that appear to be caused by oxidative stress
What samples are required?
A blood sample taken from a vein in the arm
What is being tested?
This test measures the activity of glucose-6-phosphate dehydrogenase (G6PD) in the blood. G6PD is an enzyme used to produce energy from glucose and to protect cells, especially red blood cells (RBCs), from the effects of oxidation. If there is not enough G6PD activity inside the red blood cells, they become more vulnerable to oxidative damage. If these red blood cells are exposed to an oxidising agent, their cell structure changes, the haemoglobin (the oxygen-carrying protein) inside them precipitates and the red blood cells break down.
G6PD deficiency is the most common enzyme defect in the world, affecting about 400 million people, according to the Nemours Foundation. Mutations or variations in the G6PD gene can lead to the production of a G6PD enzyme with reduced function and stability. This shows up as reduced levels of enzyme activity
More specifically, more than 350 variations of the G6PD gene have been identified, but only a few of them are common. They cause deficiencies of enzyme activity of varying severity, depending on the mutation and the patient. Since the G6PD gene is located on the X chromosome, of which males have only one copy, males will have G6PD deficiency if their G6PD gene is mutated. Females have two X chromosomes and two G6PD genes. Heterozygous females (i.e. those who carry only one mutated gene) produce both red blood cells with G6PD deficiency and red blood cells without it. They often have no symptoms and may not be identified unless the deficiency is found in their sons. Rarely, a female may be homozygous, with two altered G6PD genes (the same or different mutations), and have G6PD deficiency.
In newborn babies, G6PD deficiency can cause persistent jaundice, yellow skin and eyes caused by high bilirubin levels. If untreated, this jaundice can lead to organ damage and learning disability. Once resolved, however, newborn jaundice does not usually come back.
Most people with G6PD deficiency can lead a normal life, but they must be warned to avoid certain medicines, foods (such as broad beans), chemicals (such as naphthalene mothballs) and infections (bacterial and viral) that can cause oxidative stress and lead to episodes of haemolytic anaemia. In haemolytic anaemia, red blood cells are destroyed at an accelerated rate, and the patient may become pale and tired as their capacity to deliver oxygen to the body falls. Most of these episodes are self-limiting, but some red blood cells may be destroyed faster than the body can replace them, so affected patients may need a blood transfusion. A small percentage of patients with G6PD deficiency may have chronic anaemia
How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?
How is it used?
The aim of measuring G6PD activity is to detect G6PD deficiency and determine its potential severity. It is requested mainly for boys, as they are more often affected, but may also be requested for girls if the doctor suspects G6PD deficiency. G6PD activity may be requested for children who had persistent jaundice as newborn babies with no other identified cause. It may also be requested for patients of any age who have had one or more episodes of haemolytic anaemia, especially if the patient had a viral or bacterial illness at the time or was exposed to a known agent (such as broad beans, a “sulfa” drug or naphthalene) in the previous 24-48 hours. Repeat G6PD measurement may occasionally be requested to confirm an initial finding.
Newborn babies are not yet routinely screened for G6PD deficiency, but it is one of 30 conditions recommended for screening by several organisations. The use of G6PD activity testing is therefore expected to grow in future.
Genetic tests are not done routinely but may be requested to determine which mutation(s) are present. Only the most common G6PD mutations are identified. If a specific mutation is known to be present in a family, tests are also carried out to detect that particular mutation.
When is it requested?
G6PD activity is measured mainly in patients who have had symptoms of anaemia (such as tiredness, pallor and a rapid heart rate) and/or jaundice. Their laboratory results may show a raised bilirubin concentration, haemoglobin in the urine, a low red blood cell count, a raised reticulocyte count (immature red blood cells, indicating increased production) and sometimes Heinz bodies (precipitated haemoglobin that can be seen inside the red blood cells under the microscope).
G6PD activity is requested for patients in whom other causes of anaemia and jaundice have been ruled out, and once the acute phase has resolved. It should not be done when a patient has been, or is about to be, admitted to hospital for a haemolytic episode. This is because the older red blood cells, which are more deficient in G6PD, are usually destroyed first, leaving the younger, less deficient cells to be tested. This can distort the results and make the activity level appear closer to normal than it really is. If the test is done during this period, it should be repeated later to confirm G6PD activity levels.
G6PD genetic testing may sometimes be carried out within a family to identify the relevant mutation in female carriers (such as the mother of an affected son or the daughter of an affected father) when one or more male family members have G6PD deficiency.
What does the test result mean?
If G6PD activity is reduced, there is G6PD deficiency of some degree. In general, the lower the activity level, the more likely the patient is to have symptoms when exposed to oxidative stress.
However, the results cannot be used to predict how an affected patient will react in particular circumstances. The severity of symptoms will vary from patient to patient and from episode to episode.
If a male patient has normal G6PD activity levels, he probably has no deficiency. However, if the test was done during an episode of haemolytic anaemia, it should be repeated a few weeks later, when the red blood cell population has had time to recover and mature.
Heterozygous females will have both types of cells, those with G6PD deficiency and those without. They will usually have normal or near-normal G6PD activity levels, and few will have symptoms. A carrier may not be identified by measuring G6PD activity. In the rare homozygous female, G6PD activity will be significantly reduced.
If a G6PD gene mutation is detected, the patient will probably have some degree of G6PD deficiency. A particular patient may have symptoms ranging from none to acute, and from severe to chronic, at different times in their life. An affected male will pass his mutation on to his daughters, who will become carriers. A heterozygous female carrier has a 50% chance of passing a mutation on to each of her children. A homozygous female will pass one of her mutations on to all her children. The mutation(s) will be the same throughout the family and may be common in a geographical region. [For more information on the use of genetic tests, see The Universe of Genetic Testing.]
Is there anything else I should know?
Although G6PD deficiency is found all over the world, it is most common in people from Africa and the Mediterranean and has also been found in people from South-East Asia. The geographical areas where it is most common are the same areas where malaria is present, and some researchers believe that G6PD deficiency gives a survival advantage against malaria (which affects the red blood cells).
Biochemical tests and electrophoresis can be used to distinguish different G6PD variants. This was used in the past to study the prevalence and activity levels of different types of enzyme, both normal and deficient, but these tests are now used almost exclusively in research
1. Why is testing for G6PD deficiency important?
2. Is it important to determine which mutation is present?
3. Should I tell a new doctor that I have G6PD deficiency if I have no symptoms?
1. Why is testing for G6PD deficiency important?
Testing allows the patient to work with their doctor and adapt to a condition that will accompany them to varying degrees throughout their life. It also allows the patient to talk with their doctor about how the condition is inherited and its potential impact on their children. By knowing about the deficiency and avoiding potentially harmful substances and situations, most people with G6PD deficiency can lead an almost normal life.
2. Is it important to determine which mutation is present?
Not for you personally, but it can help detect the mutation in other family members. Genetic tests are usually used for the most common mutations. If a particular mutation is known to be present in a family, it can be tested for.
3. Should I tell a new doctor that I have G6PD deficiency if I have no symptoms?
Yes, this is an important part of your medical history and will affect future treatment and clinical decisions. Your doctor needs to know whether you have G6PD deficiency or are a carrier without symptoms.