G6PD
At a Glance
Why Get Tested?
To determine whether you have an inherited G6PD deficiency
When to Get Tested?
If a child experienced persistent jaundice as a newborn that was not due to another identified cause; when you have had one or more intermittent bouts of hemolytic anemia that appear to be due to an oxidative stress
Sample Required?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
None
The Test Sample
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 (see a list of drugs and foodstuff to avoid), it changes their cellular structure, precipitating hemoglobin inside the cells (Heinz Bodies), causing them to break apart (hemolysis).
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 in Southeast Asians. 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, the single X chromosome will carry the G6PD gene, thus resulting in a G6PD deficiency if the abnormal gene is inherited from the person’s 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, sulfonamides, quinine), foods (such as fava beans), and chemical substances (such as naphthalene, found in moth balls), which can cause oxidative stress resulting in a hemolytic crisis. Infections, either bacterial or viral, can also cause oxidative stress and lead to bouts of hemolytic anemia. With hemolytic anemia, RBCs are destroyed at an accelerated rate and the patient becomes pale and fatigued (anemic) as their capacity for providing oxygen to their body decreases. In some cases, jaundice can also be present during episodes of hemolysis. 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. A small percentage of those affected with G6PD may experience chronic anemia.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
The Test
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 hemolytic anemia. If the patient had a recent viral or bacterial illness or was exposed to a known trigger (such as fava beans, a “sulfa” drug, or naphthalene), followed by a hemolytic 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 hemolysis; 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 deficient cells were desteroyed.
Newborns are not yet routinely screened for G6PD deficiency, but it is one of the 30 disorders that is recommended for screening by several organizations, including the March of Dimes. Genetic testing is not routinely done but can be ordered 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 ordered?
G6PD testing is primarily performed on patients who have had symptoms of anemia (such as fatigue, pallor, a rapid heart rate) and/or jaundice. Their laboratory test results may show increased bilirubin concentrations (bulirubinemia), hemoglobin in the urine (hemoglobinuria), a decreased RBC count, an increased reticulocyte count, and sometimes the presence of Heinz bodies inside the RBCs.
G6PD activity testing is ordered on patients in whom other causes of the anemia and jaundice have been ruled out and is ordered once the acute incident has been resolved. It should not be performed when a patient is having or recovering from a hemolytic 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.
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 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 hemolytic anemia, 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 will likely have some degree of G6PD deficiency. An individual patient may experience symptoms that range from nonexistent to acute and severe to chronic at various times throughout their life. An affected male will pass the mutation on to his daughter, who will be a carrier. A heterozygous/carrier female has a 50% chance of passing it on to each of her children. A homozygous female will pass one of her mutations to all of her children. 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 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
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Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 497-498.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 456-457.
Ben-Joseph, E. (2006 August, Reviewed). G6PD deficiency. Nemours Foundation, KidsHealth for Parents [On-line information]. Available online at http://kidshealth.org/parent/general/aches/g6pd.html through http://kidshealth.org. Accessed on 8-27-08.
Matsui, W. (2007 February 26, Updated). Glucose-6-phosphate dehydrogenase deficiency. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000528.htm. Accessed on 8-27-08.
Henningson, C. (2007 March 22, Updated). Glucose-6-phosphate dehydrogenase. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003671.htm. Accessed on 8-27-08.
(2006 May, Reviewed). Glucose-6-phosphate dehydrogenase deficiency. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition=glucose6phosphatedehydrogenasedeficiency through http://ghr.nlm.nih.gov. Accessed on 8-27-08.
(2006 September). What is Hemolytic Anemia. NHLBI [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/ha/ha_whatis.html through http://www.nhlbi.nih.gov. Accessed on 8-27-08.
G6PD Deficiency Favism Association, What is G6PD Deficiency? Available online at http://www.g6pd.org/favism/english/index.mv?pgid=intro through http://www.g6pd.org. Accessed September 2008.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp 449-450.
(© 2004). Glucose-6-Phosphate Dehydrogenase. ARUP's Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_a266.jsp#1149592 through http://www.aruplab.com.
Pradell, L. (2003 January, Reviewed). G6PD deficiency. KidsHealth, Nemours Foundation [On-line information]. Available online at http://kidshealth.org/parent/general/aches/g6pd.html through http://kidshealth.org.
Lica, L. (©2001 – 2004). Glucose-6-phosphate dehydrogenase deficiency. Blueprint for Health, Blue Cross and Blue Shield of Minnesota [On-line information]. Available online at http://blueprint.bluecrossmn.com/article/gale/100084627 through http://blueprint.bluecrossmn.com.
Dhaliwal, G. et. al. (2004 June 1). Hemolytic Anemia. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20040601/2599.html through http://www.aafp.org.
Cutler, C. (2003 September 14, Updated). Glucose-6-phosphate dehydrogenase deficiency. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000528.htm through http://www.nlm.nih.gov.
Cutler, C. (2003 August 18, Updated). Hemolytic crisis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003270.htm through http://www.nlm.nih.gov.
Elstrom, R. (2001 October 25, Reviewed). Glucose-6-phosphate dehydrogenase deficiency. University of Maryland Medicine [On-line information]. Available online at http://www.umm.edu/ency/article/000528.htm through http://www.umm.edu.
(© 2004). Newborn Screening Tests. March of Dimes [On-line information]. Available online at http://www.modimes.org/pnhec/298_834.asp through http://www.modimes.org.
WHO Working Group, Beutler, E. et. al. (1989). Glucose-6-phosphate dehydrogenase deficiency [64 paragraphs]. Bulletin of the World Health Organization 67 (6): 601-611. [On-line journal]. PDF available for download at http://whqlibdoc.who.int/bulletin/1989/Vol67-No6/bulletin_1989_67(6)_601-611.pdf through http://whqlibdoc.who.int.
Beutler, E. (© 1996-2004). Erythrocyte disorders: Anemias due to increased destruction of erythrocytes with enzyme deficiencies Glucose-6-phosphate dehydrogenase deficiency. G6PD Deficiency favism association [On-line article from Williams' HEMATOLOGY]. Available online at http://www.rialto.com/favism/english/index.mv?pgid=beutler_01 through http://www.rialto.com.
The Ness Foundation: What is Oxidative Stress? Available online at http://www.ness-foundation.org.uk/What-is-Oxidative-Stress.html through http://www.ness-foundation.org.uk.
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