What to Know About G6PD Deficiency

Updated on July 11th, 2019

What's In This Guide?

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    What Is G6PD Deficiency?

    G6PD is short for Glucose-6-Phosphate Dehydrogenase. It is an enzyme that helps red blood cells work and protects those cells from substances in the blood that could harm them.

    G6PD deficiency is a genetic disorder that takes place when the red blood cells are not able to make enough G6PD or what they do make does not work the right way.

    When this happens, red blood cells break apart in an action known as hemolysis. When a large number of red blood cells are actually destroyed, it is known as hemolytic anemia. This can result in being tired, dizzy and other symptoms.

    Red blood cells that are deficient in G6PD are sensitive to some foods, medicines and infections. These triggers can cause a rapid loss of red blood cells in a short period of time in what is known as hemolytic crisis.

    When the triggers are removed, symptoms will usually stop. Although in some cases, G6PD deficiency will result in chronic anemia with or without the exposure to triggers 1.

    G6PD deficiency is known as an enzymopathy and is the most common of all these types of conditions, affecting about 400 million people worldwide 2.

    It exists in concentrated pockets in Africa, the Middle East, and Southeast Asia. In these regions, it can affect 5-30% of the population. It afflicts males the vast majority of the time.

    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 G6PD deficiency takes place more often in Mediterranean populations.

    In addition, about 1 in 10 African-American males are affected in the United States.

    Another relatively common G6PD variant is found in people of Sephardic Jewish or Sardinian descent. There is also another somewhat common variant that is present in some individuals of southern Chinese descent.

    It 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 can lead to life-threatening conditions due to hemolytic anemia. Hemolysis is triggered by infections, hyperglycemia, certain foods, and certain medications.

    G6PD deficiency can be detected through several means. The most common of these is to conduct a quantitative laboratory assay for G6PD enzyme activity.

    A G6PD enzyme activity level below 5 units per gram of hemoglobin constitutes deficiency.

    Genetic testing can be performed to confirm the diagnosis. Current practices typically do not include routine testing for the disease, but 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

    What causes G6PD Deficiency?

    G6PD deficiency is caused by mutation in the G6PD gene. Genes provide instructions for creating proteins that play critical roles in how a body functions.

    When a mutation takes place, the resulting protein may be not work right or efficient or may be absent altogether.

    When a G6PD gene mutation takes place, the resulting enzyme alone does not create any outward symptoms. For symptoms to appear, the mutated G6PD gene must interact in concert with a specific environmental factor.

    The G6PD gene contains instructions for creating (encoding) an enzyme known as glucose-6-phosphate dehydrogenase. As part of a chemical reaction, this enzyme brings about (catalyzes) the coenzyme NADPH, which protects cells from oxidative damage.

    A mutation in the G6PD gene results in low levels of functional glucose-6-phosphate dehydrogenase. When this happens, it leads to low levels of NADPH and a reduction of an antioxidant known as glutathione.

    Glutathione is necessary to protect a cell’s hemoglobin and its red cell membrane wall from highly reactive oxygen radicals. This is known as oxidative stress.

    The reduction in NADPH makes red blood cells more susceptible to destruction from oxidative stress than other cells. When this happens, they break down prematurely when certain triggering factors are introduced such as certain medications or foods.

    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.

    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.

    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.

    An X-linked Genetic Disorder

    G6PD deficiency is an X-linked genetic disorder. It is inherited and children are born with it because it was passed down from one or both parents.

    Where there are cases of a family history of the condition, the gene responsible for G6PD is on the X chromosome.

    In other cases, a mutation occurs as a new mutation, which means that the gene mutation occurred at the time of the formation of the egg or sperm for that child only, and no other family member will have the mutation.

    X-linked disorders affect males and females differently. A male has one X-chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease.

    Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers if the other X chromosome from their mother is normal.

    A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

    Females have two X chromosomes. 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.

    Daughters of female carriers of an X-linked disorder have a 50% chance of being carriers themselves, whereas boys have a 50% chance of being affected.

    Signs and Symptoms of G6PD Deficiency

    Most people with G6PD deficiency don’t have any symptoms. Others might have symptoms of hemolytic anemia if a lot of red blood cells are destroyed.

    Signs and symptoms can include:

    • 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. Very low erythrocyte counts may result in shortness of breath, dizziness, headache, cold extremities, pallor, and chest pain.

    If hemolysis is severe enough, jaundice may occur.

    Oddly enough, 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 occurs most frequently in areas of the world where malaria is common 3.

    How G6PD Deficiency is Treated

    Treating G6PD deficiency symptoms can be as simple as removing the triggering reason. With many people, this means treating the infection or stopping the use of a triggering drug. Some of these medicines include:

    Drugs to avoid by G6PD deficiency patients 4

    1. Diamino diphenyl sulfone (Dapsone)
    2. Flutamide (Eulexin)
    3. Furazolidone (Furoxone)
    4. Isobutyl nitrite
    5. Methylene blue
    6. Niridazole (Ambilhar)
    7. Nitrofurantoin (Furadantin)
    8. Phenazopyridine (Pyridium)
    9. Primaquine
    10. Rasburicase (Elitek)
    11. Sulfacetamide
    12. Sulfanilamide
    13. Sulfapyridine

    Drugs to use with caution in therapeutic doses for patients With G6PD deficiency 5

    1. Acetaminophen (Tylenol)
    2. Acetylsalicylic acid (aspirin)
    3. Antazoline (Antistine)
    4. Antipyrine
    5. Ascorbic acid (vitamin C): intravenous doses only reported
    6. Benzhexol (Artane)
    7. Chloramphenicol
    8. Chlorguanidine (Proguanil, Paludrine)
    9. Chloroquine
    10. Colchicine
    11. Diphenyldramine (Benadryl)
    12. Glyburide (glibenclamide, Diabeta, Glynase)
    13. Isoniazid
    14. L-Dopa
    15. Quinine
    16. Streptomycin
    17. Sulfacytine
    18. Sulfadiazine
    19. Sulfaguanidine
    20. Sulfamethoxazole (Gantanol)
    21. Sulfisoxazole (Gantrisin)
    22. Trimethoprim
    23. Tripelennamine (Pyribenzamine)
    24. 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 6.

    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 is through preventative measures. Part of this includes being screened for the G6PD 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 medications, the 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 (bili lights) that alleviate the jaundice. Transfusions may also be required in these circumstances as well.

    In all cases, genetic counseling may be a big benefit for patients and their families.

    Generally, the prognosis for G6PD-deficient patients is quite good. Most patients live relatively normal lives as long as they avoid triggers.

    A child should not come in close contact with mothballs (naphthalene is a trigger). Children with a G6PD deficiency should also not eat fava beans. Children and adults should also avoid red wine, all beans, blueberries, soya products, and tonic water.

    In some cases, symptoms that may appear to be G6PD deficiency are actually a similar disorder instead. They are also characterized by anemia due to the premature destructions of red blood cells.

    These disorders include acquired autoimmune hemolytic anemia, pyruvate kinase deficiency, cold antibody hemolytic anemia, warm antibody hemolytic anemia, hereditary spherocytosis, and sickle cell anemia.

    Risk Factors for G6PD Deficiency

    You may have a higher risk of having G6PD deficiency if you:

    • are male
    • are African-American
    • are of Middle Eastern descent
    • have a family history of the condition

    Risk factor triggers of hemolysis in kids with G6PD deficiency include:

    • illness, such as bacterial and viral infections
    • some painkillers and fever-lowering drugs
    • some antibiotics (most often those with “sulf” in their names)
    • some antimalarial drugs (most often those with “quine” in their names)
    • fava beans (also called broad beans)
    • naphthalene (a chemical found in mothballs and moth crystals). Mothballs can be very harmful if a child swallows one.

    Possible Complications of G6PD Deficiency

    Babies with G6PD deficiency can appear normal at birth. Others may experience serious neonatal jaundice and hemolysis that can cause neurologic damage or even death.

    Infants with G6PD deficiency with newborn jaundice and may require close monitoring for associated complications during the newborn period. Otherwise, to treat G6PD deficiency means to avoid the triggers that produce symptoms.

    For an infant, this means avoiding several medications routinely prescribed for infections and illness. It means paying strict attention to the ingredients of prepared foods and restaurant meals because fava beans are a frequent addition to prepared foodstuffs.

    The adverse effects of infection on patients with G6PD deficiency can be acute and life threatening. Over exertion from exercise and work leading to dehydration and hypoglycemia can exacerbate symptoms.

    This premature destruction of red blood cells is called hemolysis. If these cells break down more quickly than the body can replace them, it can lead to excess tiredness, shortness of breath, and rapid heart rate.

    In severe cases, it can even lead to kidney failure or death. That’s why seeking immediate treatment is so important.

    In some cases, hemolytic anemia can occur. This is a life threatening and chronic condition that requires added scrutiny for an extended period.

    It is ongoing and occurs without the need for a triggering factor. These individuals may be referred to as having a type of congenital nonspherocytic hemolytic anemia.

    People with this condition are almost always male and usually develop neonatal jaundice. Affected children may also have an enlarged spleen.

    Most people with hemolytic anemia have a mild to moderate anemia, but severe, transfusion-dependent anemia can develop as well as the severe complications of hypovolemic shock or acute kidney failure.

    How is G6PD Deficiency Diagnosed?

    A doctor can diagnose G6PD deficiency by performing a simple blood test that checks for G6PD enzyme levels. Other tests that may be done can include a complete blood count, reticulocyte count, or a serum hemoglobin test.

    All of these focus on the red blood cells in a patient’s body.

    In addition to testing for G6PD deficiency, they can also help a medical professional diagnose hemolytic anemia.

    Overall, a diagnosis will be a combination of blood tests, identifying physical symptoms, a thorough clinical evaluation and a patient history.

    Genetic testing can detect mutations in the specific gene known to cause G6PD, but is available only as diagnostic service at specialized laboratories.

    Unless there is a known family history or symptoms present themselves, screening or diagnostic tests are not always done. This means people can go through life with a mild case of G6PD deficiency and not even know it.

    If a blood test is taken during or just after a hemolysis episode, the result could produce a false normal result. The false-negative result could happen because most of the blood cells with greater G6PD deficiency have already been destroyed and the remaining blood cells are not yet or not at all G6PD-deficient.

    If a baby’s screening result is out of the normal range, additional testing may be required. An out-of-range result does not necessarily mean a baby has G6PD deficiency. A false positive result may be produced is the initial blood sample was too small or the test was performed too early.

    DNA Tests Currently Available for G6PD

    There are several companies and laboratories that offer G6PD deficiency testing. Two of the more well-known are:

    Invitae currently offers a genetic Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Test.

    This test may be appropriate for jaundiced newborns, depending on their family history, ethnicity, and response to therapy and those with hemolytic anemia.

    Patients with low levels of the G6PD enzyme on biochemical analysis can be confirmed with molecular testing. Turnaround time for results is two to three weeks.

    Tested individuals will be required to either supply a whole blood or saliva sample. You can request a sample test kit as part of the test process.

    23andMe also offers a Genetic health Risk Report for G6PD deficiency. 23andMe’s test doesn’t diagnose G6PD deficiency. Instead, it detects the most common variant linked to G6PD deficiency in people of African descent.

    This variant can also be found in people who are only partly of African descent, including people of Hispanic or Latino descent.

    Can G6PD Deficiency be Cured?

    No, but with proper care and treatment, the vast majority of symptoms can be alleviated.

    This involves removing food and medicine triggers or other environmental factors that can cause symptoms to flare up.

    When the condition is identified through newborn screening and properly managed, children with G6PD deficiency often can lead healthy lives.

    The Prognosis of G6PD Deficiency

    The outlook for people with G6PD deficiency is good. In fact, many people never have any symptoms.

    Those who do completely recover from their symptoms most of the time after treatment is received for the underlying trigger of the condition. The key is to learn how to manage the condition and prevent symptoms from developing.

    This involves avoiding foods and medications that can trigger the condition. Reducing stress levels is also another good way to control symptoms.

    Your doctor will have a list of medications and foods that you should avoid. In general, these will include certain antibiotics, especially sulfa drugs and quinolone antibiotics.

    Also avoid malaria medications, medications used in cancer treatments, such as rasburicase, aspirin, mothballs, henna, and fava beans which may include peas, lentils and peanuts.

    Is G6PD deficiency life threatening?

    Yes, it can be.

    Hemolytic anemia is the most common life-threatening manifestation of G6PD deficiency.

    In a typical course, patients present with findings of jaundice, fatigue, back pain, tachypnea, and tachycardia.

    Relevant laboratory findings include decreased hemoglobin and red blood cell counts, reticulocytosis, increased lactate dehydrogenase, and increased unconjugated bilirubin.

    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. Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficient Patients: Implications for Pharmacy.
      Jeff Bubp, PharmD, Marilyn Jen, and Karl Matuszewski, MS, PharmD. 2015 Sep.
    5. Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficient Patients: Implications for Pharmacy.
      Jeff Bubp, PharmD, Marilyn Jen, and Karl Matuszewski, MS, PharmD. 2015 Sep.
    6. G6PD Deficiency.
      Reviewed by Karen Gill, MD. Healthline. December 3, 2018.