The test measures the activity in the blood of an enzyme called glucose-6-phosphate dehydrogenase (G6PD).
G6PD serves to protect cells, especially red blood cells, from the effects of a process called oxidation which consists in the loss of electrons to the advantage of another substance that captures them.
If the activity of G6PD inside the red blood cells is insufficient, they become more vulnerable and are unable to counteract the loss of electrons. In particular, as regards the red blood cells, the oxidation can also involve a protein important for the transport of oxygen to the whole body: hemoglobin. When this happens, hemoglobin binds to the membrane of red blood cells and causes their death by lysis (rupture of the cell membrane).
G6PD deficiency is the most common enzyme defect in the world. The most affected regions are the Mediterranean area, sub-Saharan Africa, the Americas (African and Hispanic populations) and south-east Asia.
Mutations in the G6PD gene (more than 180 molecular variants are known) can lead to the production of an enzyme with reduced function, stability and activity.
The G6PD gene is located on the X chromosome (Xq28). This means that the most severe form of the disease occurs in males (who have only one X chromosome in their genetic makeup) with only one mutated G6PD gene, and in females (who have two X chromosomes in their genetic makeup) with both mutated genes. . Conversely, females who have only one mutated X gene are healthy carriers or develop mild disease.
Most people with G6PD enzyme deficiency have no disorders (symptoms), lead a normal life, do not know they are a carrier of the defect and can develop a disease only in specific circumstances.
The neonatal period, in children with this enzyme defect, can be critical because they have an increased risk of developing persistent neonatal jaundice (kernicterus) which manifests itself with yellowing of the skin and eyes caused by high levels of bilirubin.
Left untreated, this form of jaundice, which usually occurs on the third day of life, can cause neurological damage and mental retardation.
In particular conditions such as, for example, following the intake of certain medicines (antimalarials, analgesics, sulfonamides, etc.), of certain foods such as beans (favism), contact with certain chemicals (such as mothballs, or dyes called henna which is extracted from a shrub of the lythraceae family) bacterial and viral infections, the destruction of red blood cells can occur (haemolytic crisis) which causes an "acute haemolytic anemia of varying severity.
This happens because these substances cause an "oxidative stress" that the red blood cells with the defective enzyme are unable to counteract and, consequently, are destroyed. In this case the patient has the feeling of fatigue caused by the decrease in the amount of oxygen that it is carried around the body due to anemia. If the anemia is severe, blood transfusions may be required.
A small percentage of patients with G6PD defect have "chronic hemolytic anemia caused by rare variants of G6PD that have" activity less than 10% of normal.The test
The test is performed on a small amount (sample) of blood drawn with a needle from the vein of the arm. In newborns, blood is drawn from the capillaries.
It can be prescribed during birth checks or to detect the disease in populations with a high frequency of the enzymatic defect (for example in Sardinia). The test can also be performed using procedures that require only a drop of blood to be deposited on the filter paper.
If the result is positive, the test must be completed with a quantitative analysis that measures the exact quantity of G6PD. This test allows to identify a possible deficit of the enzyme and to determine its severity in males and females (with a double mutation). it is not possible without a family study and a "genetic analysis."
Genetic testing is usually not done in normal controls, but may be required to determine which mutations (s) are present. Some are more common in certain geographic areas (for example, in Italy, the Mediterranean G6PD, Seattle, A-, Union and Cassano) and therefore the analysis first involves the search for the most common mutations and only subsequently, if necessary, the " study on the whole G6PD gene.
When it is prescribed
The measurement of G6PD activity is mainly performed on people who have had disorders (symptoms) related to anemia (such as fatigue, paleness, rapid heart rate) and / or jaundice (yellowing of the eyes and skin).
The results of their laboratory tests show an increase in the concentration of bilirubin, hemoglobin in the urine, a decrease in the number of red blood cells, and an increase in the number of reticulocytes (immature red blood cells indicating an increase in their production).
Sometimes the presence of the so-called Heinz bodies (precipitated hemoglobin) inside the red blood cells is observed under the microscope.
The measurement of the activity of the G6PD should be prescribed only after the acute phase of the disease has been overcome and after some time from a possible transfusion. It should not be done during a haemolytic crisis because the result could be distorted and show a higher level of enzyme activity than it actually is. In fact, during the haemolytic crisis, older and more G6PD-deficient red blood cells are destroyed and only those that are younger and with a higher G6PD enzymatic activity remain visible.The test should be performed after a few weeks to allow time for the red blood cells to repopulate and mature.
The measure of G6PD activity can be prescribed to children who have persistent jaundice, not attributable to any other cause.
It can also be requested from people of all ages who have had one or more episodes of haemolytic anemia, especially in conjunction with viral or bacterial infections, or have been exposed, in the 24-48 hours prior to the onset of the crisis, to substances potentially responsible for the its onset (such as broad beans, mothballs, or some medications). Repeat measurement of G6PD may be requested on an occasional basis to confirm an initial picture.Results
The results of the analyzes (reports) provided by the laboratory should indicate, for each test, the ranges within which the values found are considered normal (reference ranges). In any case, even with normal results, it is advisable to show them to the attending physician who, knowing the health status of his clients, can evaluate and interpret them correctly.
The results of the G6PD test, in fact, vary according to the method used to detect them and to a series of factors such as the age of the person, sex, the reference population. Infants, for example, have higher normal G6PD values of adults, people with thalassemia (frequent in some Mediterranean areas) and G6PD defect will have normal values defined by comparison with those of thalassemia people who do not have the enzyme defect.
In general, the lower the activity level of G6PD, the greater the likelihood that the person will have disturbances (symptoms) if they are exposed to factors that can cause oxidative stress.
The severity of the complaints can vary from person to person, from episode to episode, or according to the type of drug taken and its dosage. The haemolytic crisis from ingestion of broad beans, for example, does not occur in all G6PD defect carriers, but only in a part of them.
If the test results of a male person show normal levels of G6PD activity, the deficiency is not present because the gene for this enzyme is on the X chromosome. Conversely, if in a woman the results show normal levels of G6PD. activity of G6PD it is not possible to exclude that the defect concerns at least one of the two X chromosomes and, therefore, that the person examined is a so-called healthy carrier ("heterozygote").
When women in a family have a G6PD deficiency, it would be advisable to undergo genetic counseling before a possible conception to assess the risk of transmissibility to the unborn child.
A sick male will transmit the G6PD defect only to daughters (since they inherit one X chromosome from the father and one from the mother) who will thus become heterozygous carriers (i.e., they will have the gene mutated in only one of the two X chromosomes, the one inherited from his father). A heterozygous female carrier has a 50% chance of passing the defect to her children, while a homozygous female (i.e. with the G6PD gene mutated on both X chromosomes) will transmit the defect to all of her children. The type of mutation will be the same throughout the family and may be common in a geographic region.Bibliography
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Luzzatto Poggi VE. Glucose-6-phospate dehydrogenase deficiency. In: Hematology of infancy and childhood. Saunders: Philadelphia, 2009, p. 883-907
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