G6PD

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 or a “sulfa” drug), 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.

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 (bulirubinaemia), 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 and 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.

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].

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.

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.