What to Know About G6PD Deficiency

Updated October 3, 2019

This article was scientifically reviewed by Aishwarya Arjunan

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A list of references is also included at the bottom of this article.

What Is G6PD Deficiency?

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD Deficiency) is a genetic condition most commonly seen in males in which the red blood cells break apart prematurely 1.

G6PD Deficiency is caused by mutations in the G6PD gene which is responsible for providing instructions to make the glucose-6-phosphate dehydrogenase enzyme.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

This enzyme is involved in the processing of carbohydrates and helps protect red blood cells from harmful substances called reactive oxygen species.

The glucose-6-phosphate dehydrogenase enzyme prevents reactive oxygen species from building up to toxic levels 2.

Mutations in the GPD6 disrupt this process and reduces the amount of glucose-6-phosphate dehydrogenase enzyme produced which in turn results in the accumulation of reactive oxygen species.

When this happens, red blood cells break apart faster than they can be replaced in the body and this is called hemolysis.

Hemolytic anemia occurs because the body cannot make up for the breakdown of red blood cells.

It is important to note that many individuals with G6PD deficiency never experience any signs or symptoms and may never know that they have the condition.

More than 400 different mutations have been found in people with G6PD deficiency. Mutations are associated with a certain amount of enzyme deficiency, but never with complete enzyme deficiency 3.

A complete deficiency is not compatible with life.

As a result, G6PD deficiency has been classified by the World Health Organization into variants based on the degree of the deficiency and the resulting symptoms 4.

  1. Class I are the most severe variants and occur where there is chronic hemolysis even in the absence of any triggering factor.
  2. Class II and III are variants with marked enzyme deficiency but no chronic hemolysis.
  3. Class IV are variants with normal enzyme activity.
  4. Class V was designed for variants with increased enzyme activity.

Individuals with G6PD deficiency can experience different symptoms due to hemolytic anemia such as paleness, fatigue, shortness of breath, jaundice (yellowing of the skin and whites of the eyes), dark urine, and a rapid heart rate.

Red blood cells that are deficient in glucose-6-phosphate dehydrogenase are sensitive to certain triggers that can cause a rapid loss of red blood cells in a short period of time causing what is known as hemolytic crisis.

When the triggers are removed, symptoms generally stop. Although in some cases, G6PD deficiency will result in chronic anemia with or without the exposure to triggers 5.

Triggers include some medicines, foods, and infections such as the following:

  • Foods
    • Fava beans
  • Medications/Chemicals
    • Certain painkillers and fever-reducing drugs
    • Certain antibiotics
    • Antimalarial drugs
    • Napthalene (a chemical very commonly found in mothballs)
  • Infections
    • Bacterial and Viral infections

How Common is G6PD Deficiency?

While G6PD deficiency can be seen in individuals of all ethnic backgrounds, it is more commonly found in males, and more specifically in individuals from Africa, the Middle East, and Southeast Asia.

Approximately 400 million people worldwide have G6PD deficiency 6. Approximately 1 in 10 African-American males are affected in the United States.

Although the number of people with G6PD deficiency is high, the vast majority of people remain clinically asymptomatic throughout their lives.

The severity of G6PD deficiency can vary based upon specific racial groups. The most severe form of the condition is seen in the Mediterranean populations.

Another relatively common G6PD variant is found in people of Sephardic Jewish or Sardinian descent.

Another common variant is present in some individuals of southern Chinese descent.

G6PD deficiency is also known worldwide as “favism” because of the hemolytic effect that fava beans can have on patients with the condition.

Fava beans are a type of legume eaten throughout the world. They contain high amounts of divicine, convicine, and isouramil which are chemicals that are suspected to be highly oxidative.

G6PD deficiency can be diagnosed shortly after birth as some newborns are screened for this condition along with a number of others within a few days of birth.

However, there are cases of some individuals who may remain unaware and asymptomatic for their entire life.

What Are the Symptoms of G6PD Deficiency?

The severity of the symptoms of G6PD deficiency varies from person to person. The vast majority of individuals remain asymptomatic (without symptoms) for their entire life and may never know that they have G6PD deficiency.

Generally, individuals with G6PD deficiency show no signs or symptoms until they are exposed to certain medications, foods, or infections.

These exposures can lead to the breakdown of red blood cells (hemolysis) and lead to hemolytic anemia.

If hemolysis occurs faster than the body’s ability to regenerate new red blood cells, than it can lead to anemia.

Signs and symptoms can include 7:

  • paleness (in darker-skinned children, paleness is sometimes best seen in the mouth, especially on the lips or tongue)
  • extreme tiredness or dizziness
  • general fatigue
  • fast heartbeat
  • fast breathing or shortness of breath
  • jaundice
  • an enlarged spleen
  • dark, tea-colored urine

Acute hemolysis may also produce back or abdominal pain. Although rare, in very severe cases it can lead to kidney failure or death.

These symptoms can be alleviated once the triggers are identified and removed.

Interestingly, researchers believe that people who have a G6PD mutation may be partially protected against malaria.

It appears that a reduction in the amount of functional glucose-6-phosphate dehydrogenase makes it more difficult for this parasite to invade red blood cells.

As a result, G6PD deficiency is observed more frequently in areas of the world where malaria is common 8.

How is G6PD deficiency diagnosed?

In the United States, some states offer newborn screening for G6PD deficiency. However, it is not routine.

A diagnosis generally comes when an individual experiences symptoms associated with the condition.

Testing should be considered in:

  1. Patients of African, Middle Eastern, or Asian descent presenting with hemolytic anemia
  2. Males with a family history of jaundice, splenomegaly, or cholelithiasis
  3. Newborns with severe jaundice

A diagnosis can be made with a quantitative spectrophotometric analysis, a rapid fluorescent spot test or genetic testing.

How is G6PD Deficiency Treated?

Treating G6PD deficiency can be as simple as identifying and removing the specific trigger.

For many people, this means treating an infection or stopping the use of a particular medication. Some of these medicines include:

Drugs to avoid by G6PD deficiency patients 9:

  • Diamino diphenyl sulfone (Dapsone)
  • Flutamide (Eulexin)
  • Furazolidone (Furoxone)
  • Isobutyl nitrite
  • Methylene blue
  • Niridazole (Ambilhar)
  • Nitrofurantoin (Furadantin)
  • Phenazopyridine (Pyridium)
  • Primaquine
  • Rasburicase (Elitek)
  • Sulfacetamide
  • Sulfanilamide
  • Sulfapyridine

Drugs to use with caution in therapeutic doses for patients With G6PD deficiency 10

  • Acetaminophen (Tylenol)
  • Acetylsalicylic acid (aspirin)
  • Antazoline (Antistine)
  • Antipyrine
  • Ascorbic acid (vitamin C): intravenous doses only reported
  • Benzhexol (Artane)
  • Chloramphenicol
  • Chlorguanidine (Proguanil, Paludrine)
  • Chloroquine
  • Colchicine
  • Diphenyldramine (Benadryl)
  • Glyburide (glibenclamide, Diabeta, Glynase)
  • Isoniazid
  • L-Dopa
  • Quinine
  • Streptomycin
  • Sulfacytine
  • Sulfadiazine
  • Sulfaguanidine
  • Sulfamethoxazole (Gantanol)
  • Sulfisoxazole (Gantrisin)
  • Trimethoprim
  • Tripelennamine (Pyribenzamine)
  • Vitamin K

In some cases of severe anemia, a patient may need to go to a hospital to get oxygen and fluids. At other times, a transfusion of healthy blood cells may be required 11.

When mild symptoms occur, they usually don’t require medical treatment. As the body makes new red blood cells, the anemia will improve.

The best way to treat G6PD deficiency is through preventative measures.

Part of this may include being screened for G6PD deficiency before being treated with antibiotics, antimalarials, and other medications that can trigger hemolysis in patients.

When hemolytic anemia takes place due to the use of a medication, the triggering drug that causes the reaction should be discontinued, but only under a physician’s supervision.

If the hemolytic anemia is due to an infection, then steps should be taken to treat the infection.

Some adults may also need to be treated through the use of fluids to prevent hemodynamic shock, which takes place when there is an inadequate supply of blood to the organs.

In more severe cases, blood transfusions may also be required.

Neonatal jaundice is treated by placing an infant under special “bili” lights that alleviate the jaundice. Transfusions may also be required in these circumstances as well.

What is the life expectancy of an individual with G6PD Deficiency?

Generally, the prognosis for individuals with G6PD Deficiency is good. Most patients live relatively normal lives as long as they avoid triggers.

Children with the condition should not come in close contact with mothballs as naphthalene a chemical found in mothballs is a trigger.

Individuals with G6PD deficiency should also not eat fava beans and avoid red wine, all beans, blueberries, soy products, and tonic water.

How is G6PD Deficiency Inherited?

G6PD deficiency is inherited in an X-linked pattern. This means that the gene associated with G6PD deficiency is found on the X-chromosome.

We have 46 chromosomes in each cell of our bodies. These chromosomes can be organized into 23 pairs.

One of each pair of chromosomes is inherited from each parent. Our genetic information, or our genes, is carried on the chromosomes.

Genes are instructions telling our bodies how to grow and develop.

The 23rd pair of chromosomes are referred to as the sex chromosomes or the “X” and “Y” chromosomes.

Females inherit two X chromosomes, one from each parent, while males inherit one X chromosome (from the mother) and one Y chromosome (from the father).

In males (who have only one X chromosome), one altered copy of the G6PD gene is sufficient to cause the condition.

In females (who have two X chromosomes), a mutation would have to occur in both copies of the G6PD gene to cause the disorder.

Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.

A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons 12.

Whether females with a mutation of G6PD gene develop a G6PD deficiency depends on a normal process known as random X-chromosome inactivation.

Because females have two X chromosomes, certain disease traits on the X chromosome such as a mutated gene may be “masked” by the normal gene on the other X chromosome.

This is known as random X- chromosome inactivation.

This means in each cell of the body one X chromosome is active and one is turned off or “silenced.” It happens randomly and generally happens as a 50-50 split.

Credit: U.S. National Library of Medicine

What are the chances that I will pass G6PD deficiency to my child?

If the mother (female) has one disease causing gene mutation, then there is a 50% chance that her sons will inherit the mutation and have G6PD deficiency and a 50% chance that her daughter will inherit the mutation and be a carrier for G6PD deficiency like her mother.

If the mother (female) has two disease causing gene mutations , then there is a 100% chance that her sons will inherit one of the two mutations and have G6PD deficiency and a 100% chance that her daughter will inherit one of the two mutations and be a carrier for G6PD deficiency.

If the father (male) has one disease causing mutation and affected with G6PD deficiency then there is a 100% chance that his daughter will inherit the mutation and be a carrier for G6PD deficiency and a 0% chance that his sons would be affected.

Genetic Testing for G6PD Deficiency

Blood testing and looking for disease causing mutations in the G6PD gene can help establish a diagnosis of G6PD deficiency.

Speak with your health care provider if you wish to learn more about genetic testing for G6PD deficiency.

A referral to a genetic counselor can be helpful to discuss the various testing options for you and your family.

Is prenatal testing available?

Genetics play a very critical part in whether a person develops the disorder, or even if they are a carrier who can pass it onto their children.

If parents want to know their risk of having a child with G6PD deficiency then they can consider getting carrier screening prior to or in the early stages of pregnancy.

Carrier screening will help identify whether there is an increased risk.

Speaking with a genetic counselor can help determine if this testing is right for you.

Where can I go to get genetic testing?

There are a variety of options available for genetic testing. Genetic testing is generally ordered by a healthcare provider though there are now a few options available for you to get testing directly from a testing company.

When considering any form of genetic testing, it can be helpful to speak with your healthcare provider to learn about the benefits and limitations of testing and testing options.

It is always advised to complete diagnostic testing under the guidance of a healthcare provider.

Testing completed through your doctor’s office usually involve a blood sample.

Companies like 23andMe and Helix offer genetic testing that can help identify carriers.

It is important to compare these screens to testing that would be ordered by your provider to confirm whether they are as comprehensive.

Some direct to consumer tests may not offer as comprehensive of a screen compared to the one that you may get from your healthcare provider.

These direct to consumer tests typically involve a saliva or buccal sample. You’ll be able to view your results online within 4-8 weeks.

It is important to note that results from at-home kits may not provide a complete answer.

DNA Testing for G6PD Deficiency: Benefits and Limitations

Genetic testing can a mix of benefits and limitations. There is no possibility of physical harm or any biological risk in getting tested aside from the general risk of a blood draw if a blood draw is completed.

Although deciding on testing is entirely voluntary, it can prove to be a complex decision that may raise new health concerns or anxieties.

For this reason, it’s best to seek genetic counseling to help discuss the emotional and social aspects of genetic testing, as well as get an educated interpretation of the results.

With that in mind, here is a short list of the strengths and limitations:

Benefits of Genetic Testing:

  1. Relief from any uncertainty about whether or not G6PD deficiency is the appropriate diagnosis.
  2. In-depth understanding about the disease and how it impacts you and your health.
  3. You will be in a position to educate your family about the potential risk of passing down the condition or help diagnose other family members who may also have G6PD deficiency.
  4. Knowing you are a carrier can help you make future family-planning decisions.

Limitations of DNA Testing:

  • Your new knowledge will not lead to a cure, but will help empower you to make decisions about your health and future
  • You may not be able to get a conclusive answer after genetic testing which may then lead to a feeling of uncertainty about the diagnosis and family planning.

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Referenced Sources

  1. G6PD Deficiency.
    KidsHealth. July 2018.
  2. Glucose-6-phosphate dehydrogenase deficiency.
    Genetics Home Reference. Retrieved online, June 2019.
  3. Glucose-6-Phosphate Dehydrogenase Deficiency.
    NORD – National Organization for Rare Disorders. Retrieved online, June 2019.
  4. Glucose-6-Phosphate Dehydrogenase Deficiency.
    NORD – National Organization for Rare Disorders. Retrieved online, June 2019.
  5. G6PD Deficiency.
    KidsHealth. July 2018.
  6. Glucose-6-phosphate dehydrogenase deficiency.
    Genetics Home Reference. Retrieved online, June 2019.
  7. Glucose-6-Phosphate Dehydrogenase Deficiency.
    NORD – National Organization for Rare Disorders. Retrieved online, June 2019.
  8. Glucose-6-Phosphate Dehydrogenase Deficiency.
    NORD – National Organization for Rare Disorders. Retrieved online, June 2019.
  9. Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficient Patients: Implications for Pharmacy.
    Jeff Bubp, PharmD, Marilyn Jen, and Karl Matuszewski, MS, PharmD. 2015 Sep.
  10. Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficient Patients: Implications for Pharmacy.
    Jeff Bubp, PharmD, Marilyn Jen, and Karl Matuszewski, MS, PharmD. 2015 Sep.
  11. Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficient Patients: Implications for Pharmacy.
    Jeff Bubp, PharmD, Marilyn Jen, and Karl Matuszewski, MS, PharmD. 2015 Sep.
  12. Glucose-6-phosphate dehydrogenase deficiency.
    Genetics Home Reference. Retrieved online, June 2019.