G6PD deficiency is an inherited condition where your red blood cells lack enough of an enzyme called glucose-6-phosphate dehydrogenase, making them vulnerable to breaking apart when exposed to certain foods, medications, or infections. It affects an estimated 443 million people worldwide, making it the most common enzyme deficiency in humans. Most people with G6PD deficiency live normal lives and only experience problems when they encounter a specific trigger.
How G6PD Protects Red Blood Cells
Red blood cells constantly face oxidative stress, a type of chemical damage caused by reactive molecules your body produces naturally and in greater amounts during illness or after exposure to certain substances. The G6PD enzyme is your red blood cells’ primary defense system against this damage. It fuels a chemical pathway that neutralizes these harmful molecules before they can destroy the cell membrane.
When the enzyme is missing or doesn’t work well enough, red blood cells can’t defend themselves. Oxidative stress punches holes in the cell wall, causing the cells to burst open. This destruction of red blood cells is called hemolysis, and when it happens rapidly, it leads to a sudden drop in red blood cell count, otherwise known as hemolytic anemia. Unlike most other cells in your body, red blood cells can’t make new proteins to replace damaged ones, so G6PD deficiency hits them especially hard.
Why It Runs in Families
The gene for G6PD sits on the X chromosome, which means the condition follows an X-linked inheritance pattern. Males have one X chromosome and one Y, so a single altered copy of the gene is enough to cause the deficiency. Females have two X chromosomes, so they’d typically need both copies altered to be fully affected.
In practice, though, many females with just one altered copy do experience symptoms. This happens because of a process called X-inactivation, where one X chromosome in each cell is randomly switched off. Research shows that women with G6PD deficiency often have skewed inactivation, meaning the chromosome carrying the normal gene gets shut down in more than half their cells, leaving the deficient version active. This is why the old idea that “only men get G6PD deficiency” is inaccurate. Women can and do experience hemolytic episodes, though severity varies more widely among women than men.
Fathers cannot pass the condition to their sons (since sons get their Y chromosome from dad), but a mother who carries one altered copy has a 50% chance of passing it to each child. The condition is most common in people with ancestry from South Asia, Sub-Saharan Africa, the Middle East, and the Mediterranean, regions where malaria has historically been prevalent. Carrying one copy of the altered gene appears to offer some protection against malaria, which is why natural selection has kept the trait common in these populations. South Asia alone accounts for roughly 138 million cases.
Severity Varies Widely
Not all G6PD deficiency is the same. The World Health Organization classifies variants into four classes based on how much enzyme activity remains:
- Class I: Severe deficiency with chronic, ongoing anemia even without triggers
- Class II: Severe deficiency (less than 10% of normal enzyme activity), but symptoms only occur with triggers
- Class III: Moderate deficiency (10 to 60% of normal activity), with milder episodes
- Class IV: Normal enzyme activity (60 to 150%), no clinical significance
Most people with G6PD deficiency fall into Class II or III. Those with Class I, the rarest and most severe form, have chronic hemolytic anemia that persists regardless of trigger exposure. For everyone else, the condition is silent between episodes.
What Triggers a Hemolytic Episode
Three main categories of triggers can set off red blood cell destruction: certain foods, specific medications, and infections.
Fava Beans
The connection between G6PD deficiency and fava beans is so well known that the condition was historically called “favism.” Fava beans contain compounds called vicine and convicine, which your body converts into potent oxidizing agents that overwhelm unprotected red blood cells. Not everyone with G6PD deficiency reacts to fava beans, and the severity of reaction varies, but they’re the single most recognized dietary trigger.
Medications
Several drugs pose a high risk for hemolysis in people with G6PD deficiency. The most dangerous include primaquine and tafenoquine (antimalarial drugs), dapsone (used for skin conditions and infections), rasburicase (a gout medication), and methylene blue (used to treat a blood oxygen condition). Medium-risk medications include nitrofurantoin, a common antibiotic prescribed for urinary tract infections. If you know you have G6PD deficiency, this is critical information to share with any prescribing provider, including urgent care and emergency physicians who may not have your medical history.
Infections
Infections are actually the most common trigger for hemolytic episodes worldwide. The body’s immune response to infection increases oxidative stress throughout the bloodstream, which can push G6PD-deficient red blood cells past their breaking point. Bacterial and viral infections alike can trigger episodes.
What a Hemolytic Episode Feels Like
Symptoms typically begin 24 to 72 hours after exposure to a trigger. You might notice dark or tea-colored urine first, which is caused by the contents of destroyed red blood cells being filtered through your kidneys. Back pain or abdominal pain is common. Fatigue and shortness of breath develop as your red blood cell count drops.
Jaundice, a yellowing of the skin and the whites of the eyes, develops when enough red blood cells have been destroyed. This yellowing generally doesn’t appear until more than 50% of red blood cells have been broken down. In mild cases, you might feel tired and notice slightly darker urine for a few days. In severe cases, the anemia can be dangerous enough to require a blood transfusion.
The good news is that episodes are self-limiting in most cases. Once the trigger is removed, the body starts producing new red blood cells to replace the destroyed ones. Recovery typically takes four to seven days, with the bone marrow ramping up production of fresh cells during that window.
How G6PD Deficiency Is Diagnosed
Diagnosis involves measuring G6PD enzyme activity in a blood sample. There are two main approaches.
The fluorescent spot test is a qualitative screening tool. A blood sample is placed under ultraviolet light, and the brightness of the fluorescence indicates enzyme activity. Bright fluorescence means normal activity; faint or absent fluorescence signals deficiency. This test reliably identifies severe deficiency but struggles with intermediate levels, which means it can miss some cases in women who have a mix of normal and deficient red blood cells.
Quantitative testing using spectrophotometry gives a precise measurement of enzyme activity and can distinguish between moderate and normal levels with much finer resolution. It requires more advanced lab equipment, so it’s not available everywhere, but it’s the more accurate option.
One important caveat: testing during or immediately after a hemolytic episode can produce a falsely normal result. That’s because the most deficient red blood cells have already been destroyed, and the remaining cells (plus newly produced ones) may have closer-to-normal enzyme levels. Testing should ideally be done when you’re well, at least a few weeks after any episode. For women with one altered gene copy, genetic testing or specialized cell-by-cell staining may be needed for accurate diagnosis, since standard enzyme tests can miss heterozygous carriers.
Living With G6PD Deficiency
For the vast majority of people, managing G6PD deficiency is about avoidance rather than ongoing treatment. There is no medication that corrects the enzyme deficiency itself. The practical steps are straightforward: know your trigger list, carry that information with you, and make sure it’s flagged in your medical records.
Children diagnosed with G6PD deficiency need their schools and caregivers informed, particularly about fava beans. Parents should also keep a list of unsafe medications accessible, since common over-the-counter drugs are generally fine but certain prescriptions can cause serious problems. During infections or fevers, staying alert to signs of hemolysis (dark urine, unusual fatigue, yellowing skin) allows for early intervention if an episode begins.
People with the rare Class I form, who have chronic hemolytic anemia, may need ongoing monitoring of their blood counts and iron levels. They may also need folic acid supplementation to support the constant production of new red blood cells. But for the much larger group with Class II or III deficiency, the condition has little impact on daily life as long as triggers are avoided.