Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that can result in increased sensitivity of erythrocytes to oxidative stress, which can lead to hemolysis (the destruction of blood cells).1 A deficiency of the G6PD enzyme impairs erythrocytes to be able to form nicotinamide adenine dinucleotide phosphate. Nicotinamide adenine dinucleotide phosphate is an important enzyme that is needed to reduce glutathione, which aids in the defense of erythrocytes against oxidative stress.1–3 Damage can occur within the cells and includes inflammation, blood vessel damage, and hemolytic anemia.2,4 The result of G6PD deficiency can be reduced energy to erythrocyte cells and hemolytic anemia.4
G6PD deficiency is one of the most common human enzyme defects.1 It affects approximately 10% of males of African American descent in the United States and approximately 7% to 8% of the global population.1,5–7 Although individuals who are most commonly affected are of African, Asian, Mediterranean, and Middle Eastern ethnic groups, geographically, North America has been an exception.1,8 Screening for the G6PD deficiency is recommended in regions where its prevalence is 3% to 5% or more, but cost, lack of awareness, and a lack of appreciation for the impact of G6PD on public health often limit detection of the deficiency.2 A serum hemoglobin test to measure the amount of hemoglobin in the blood can detect G6PD deficiency.9 The presence of bite cell deformities and Heinz bodies in erythrocytes leak hemoglobin into the bloodstream and indicates a positive test for G6PD deficiency.9
Most G6PD deficient individuals are asymptomatic throughout their life and unaware of their status.2 If an individual is G6PD deficient, symptomatic signs and symptoms include anemia, hemolysis, back pain, abdominal pain, jaundice, splenomegaly, and hemoglobinuria.9 The bite cells leak hemoglobin into the blood circulation during hemolysis, which causes hemoglobinuria. There may be unique food or environmental triggers of hemolysis that accompany a G6PD deficiency. The triggers that have been reported include: fava beans, medication, stress from a bacterial or viral infection, oxidative stress, long sunlight exposure, and dehydration.9
The purpose of this case review is to identify a successful, conservative approach to clinically manage G6PD deficiency in a high school basketball athlete.
In 2015, an 18-year-old African American male high school basketball athlete (weight: 102.06 kg, height: 198.12 cm) presented to the athletic trainer with symptoms of dizziness, fatigue, lower extremity body muscle cramps, and blurred vision. These symptoms were accentuated after basketball-related activities that involved a high amount of cardiovascular exertion for prolonged periods, such as drills that involved sprinting and during basketball games, which led the patient to seek medical attention. The patient also experienced symptoms when vigorous exercise was combined with a hot and humid environment. He was known to be negative for sickle cell trait disease. The patient was discharged from the emergency department with a diagnosis of dehydration and syncope with no participation limitations.
Within a few months of his initial emergency department visit, the patient experienced fatigue, dizziness, and lower extremity body cramping that made him seek medical attention again. A urinalysis was ordered during the second emergency department visit and revealed hemoglobin in the urine sample (hemoglobinuria). The patient was treated with intravenous fluids, discharged from the emergency department, and instructed to follow up with his family physician after both emergency department visits. He was withheld from participation until he received clearance from his physician because of the reoccurrence of his symptoms after his second emergency department visit.
Due to the aforementioned symptoms, serum hemoglobin analysis was ordered and reviewed by his physician. The serum hemoglobin analysis test showed bite cell deformities and the presence of Heinz bodies. The blood serum test confirmed a diagnosis of G6PD deficiency.
For the next 2 to 3 years, the patient found, through trial and error, that his symptoms would present after ingesting any type of bean, hot dogs, green and black tea, and all types of peas. According to the current literature, hot dogs and peas are uncommon triggers, but every patient has sensitivity to different foods.10 Additionally, dehydration, moderate to extreme heat, long exposure to sunlight, and high intensity endurance or anaerobic exercise including running or weight lifting contributed to the patient's symptomology.
Athletic trainers may not be familiar with G6PD deficiency etiology or symptomology because of the lack of education available on the topic. Appropriate recognition and clinical management is necessary to ensure a safe, monitored environment. The first step to clinical management of G6PD deficiency is to prevent a hemolytic episode by identifying symptoms early and controlling the amount of oxidative stress the patient experiences. Because oxidative stress indicates the exercise intensity (eg, sprinting), the athletic trainer monitored our patient carefully during practices and events while communicating with the coaching staff to determine appropriate practice limitations. The athletic trainer worked with the patient and coaching staff to include extra breaks during workouts. Furthermore, because the patient previously experienced symptoms associated with hemolysis with moderate to extreme heat, intermittent breaks and resting in a shaded, cooled environment was a successful conservative management plan.
The second step in prevention is to identify the different types of food and external conditions that may trigger a G6PD deficiency episode. It is also important to note that other triggers for individuals with G6PD deficiency include food and external conditions within the environment that can cause immediate hemolysis.1 The triggers identified in the literature include: infectious diseases such as salmonella or malaria that cause hemolysis associated with white blood cell release during the phagocytosis process, drug-induced hemolysis, or fava bean ingestion.8 In some cases, different types of over-the-counter and prescription drugs may cause acute hemolysis in individuals who have a G6PD deficiency, although most of the time patients recover 4 to 7 days after the episode.8
Modifications to diet and exercise to clinically manage a case such as this are extremely important. In this case, best practices for hydration and cooling were implemented to monitor and help minimize the environmental effects on the body.11 The athletic trainer educated the patient on proper hydration techniques and the patient was given a urine chart to monitor urine color. This allowed the patient to have an objective way to independently monitor hydration. The patient was instructed to keep the urine color at a clear to light yellow color range.11 The second reason to monitor the urine was to work toward preventing a G6PD deficiency episode by monitoring hydration status. In the event the urine became darker, the patient could then begin to hydrate more to prevent an attack. Athletic trainers should use fluid replacement best practices to ensure proper hydration.11
Implications for Clinical Practice
Individuals may have G6PD deficiency but are unaware of their trait status. Although G6PD deficiency is one of the most common enzyme-related disorders,12 it is not a part of a standardized screening tool in athletic training. For example, sickle cell status, difficulty breathing with exercise, heart murmur, and chest pain with exercise are a few standard questions asked on preparticipation questionnaires used by athletic trainers to identify the potential for life-threating conditions.13 There are no specific questions that identify G6PD status. Therefore, it is important for athletic trainers to consider implementing questions that can be related to the signs and symptoms of an individual with G6PD deficiency, which include unusual fatigue, prior or current anemia, or inability to exercise at normal levels.8 If there are indications in the medical history review that the athlete has experiences with any of these symptoms, follow-up questions concerning nutritional behaviors may be warranted.
It has been suggested that folic acid and iron can be beneficial to a patient who has previously experienced hemolysis.8 Furthermore, creating a health care team to treat the patient with G6PD deficiency is critical to ensure a safe environment for participation in activities. By correctly managing or preventing a hemolytic episode in an athlete or patient with G6PD deficiency, there is an overall potential to decrease the mismanagement of this genetic disorder. There may also be further medical complications such as red blood cell damage, hemolytic anemia, jaundice, rapid heart rate, fatigue, and shortness of breath.8,9
Another factor to consider that may help to prevent the occurrence of hemolysis secondary to a G6PD deficient individual is to monitor the intensity of exercise. This can be done by keeping heart rate levels at approximately 75% of maximum heart rate as a way to decrease the incidence of oxidative stress that occurs in the body due to exercise.8,14 Based on published literature, avoiding or reducing the risk for oxidative stress is the most common way to avoid hemolysis and symptoms linked with G6PD deficiency.8 Comparatively, one study showed that long-term, regular exercise may provide a protective effect on oxidative stress and may help to decrease the effects of intense oxidative stress on those individuals with G6PD deficiency.14
This case review highlights the awareness of the G6PD deficiency genetic disorder. There does not appear to be a standard of practice for clinicians to treat or manage this specific condition. Part of the reason for the lack of research is that many affected individuals are asymptomatic until a trigger is introduced to cause a hemolytic event in a patient. This case review demonstrates that with patient education, hydration, and nutrition management, alteration with activity is successful in managing the active individual with a G6PD deficiency as opposed to completely restricting physical activity.
- Manganelli G, Masullo U, Passarelli S, Filosa S. Glucose-6-phosphate dehydrogenase deficiency: disadvantages and possible benefits. Cardiovasc Hematol Disord Drug Targets. 2013;13(1):73–82. doi:10.2174/1871529X11313010008 [CrossRef]23534950
- Jelani I, Garba N, Raji AY. Public awareness of glucose-6-phosphate dehydrogenase deficiency in sokoto. Int J Med Biomed Res. 2016;5(1):50–56. doi:10.14194/ijmbr.5.1.7 [CrossRef]
- Kaldirimci M. Effect of a 12-week training program on levels of glucose-6-phosphate dehydrogenase and antioxidant activity. Turk J Rheumatol. 2010;25(1):34–36. doi:10.5152/akd.2010.06 [CrossRef]
- Tiwari M. Glucose 6 phosphatase dehydrogenase (G6PD) and neuro-degenerative disorders: mapping diagnostic and therapeutic opportunities. Genes Dis. 2017;4(4):196–203. doi:10.1016/j.gendis.2017.09.001 [CrossRef]
- Beutler E. G6PD: population genetics and clinical manifestations. Blood Rev. 1996;10(1):45–52. doi:10.1016/S0268-960X(96)90019-3 [CrossRef]8861278
- Hoiberg A, Ernst J, Uddin DE. Sickle cell trait and glucose-6-phosphate dehydrogenase deficiency. Effects on health and military performance in black Navy enlistees. Arch Intern Med. 1981;141(11):1485–1488. doi:10.1001/archinte.1981.00340120093019 [CrossRef]7283560
- Nikolaidis MG, Jamurtas AZ, Paschalis V, et al. Exercise-induced oxidative stress in G6PD-deficient individuals. Med Sci Sports Exerc. 2006;38(8):1443–1450. doi:10.1249/01.mss.0000228938.24658.5f [CrossRef]16888458
- Waryasz GR. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and exercise. Athl Ther Today. 2009;14(3):26–31. doi:10.1123/att.14.3.26 [CrossRef]
- Frank JE. Diagnosis and management of G6PD deficiency. Am Fam Physician. 2005;72(7):1277–1282.16225031
- Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371(9606):64–74. doi:10.1016/S0140-6736(08)60073-2 [CrossRef]18177777
- McDermott BP, Anderson SA, Armstrong LE, et al. National Athletic Trainers Association Position Statement: fluid replacement for the physically active. J Athl Train. 2017;52(9):877–895. doi:10.4085/1062-6050-52.9.02 [CrossRef]28985128
- Bubp J, Jen M, Matuszewski K. Caring for glucose-6-phosphate dehydrogenase (G6PD)-deficient patients: implications for pharmacy. P T. 2015;40(9):572–574.26417175
- Conley KM, Bolin DJ, Carek PJ, Konin JG, Neal TL, Violette D. National Athletic Trainers' Association Position Statement: preparticipation physical examinations and disqualifying conditions. J Athl Train. 2014;49(1):102–120. doi:10.4085/1062-6050-48.6.05 [CrossRef]24499039
- Jamurtas AZ, Fatouros IG, Koukosias N, et al. Effect of exercise on oxidative stress in individuals with glucose-6-phosphate dehydrogenase deficiency. In Vivo. 2006;20(6B):875–880.
- Memorang, Inc. Pathology II – Block I website https://www.memo-rangapp.com/flashcards/136197/Pathology+II+-+Block+I/. Accessed November 8, 2018.