Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

How G6PD deficiency causes hemolysis

Red blood cells carry oxygen and are constantly exposed to oxidizing chemicals. G6PD is the key enzyme that produces NADPH, which keeps protective glutathione active. Without enough G6PD, red cells cannot defend themselves when oxidative stress rises. Hemoglobin is damaged, forms clumps (Heinz bodies), and the cells are destroyed in the blood vessels and spleen.

Hemolysis usually starts 1 to 3 days after exposure to a trigger. Because younger red cells have more enzyme, episodes are often self-limiting once the oldest cells are destroyed, provided the trigger is removed.

Who has G6PD deficiency

The gene is on the X chromosome:

• Males with one affected gene are deficient.
• Females with two affected genes are deficient; those with one may have normal, intermediate or low activity.

It is common where malaria was historically widespread, because the deficiency gives partial protection against malaria. Severity varies by genetic variant. The Mediterranean variant tends to cause more severe hemolysis than the common African variant.

Triggers to avoid

Foods

• Fava (broad) beans, fresh or dried; reactions are called favism and can be severe, especially in children.
• Some people are advised to avoid products with fava bean derivatives. Other legumes are generally safe.

Medicines

Commonly listed medicines that can trigger hemolysis include:

• Antimalarials: primaquine and tafenoquine (testing is required before use)
• Dapsone
• Rasburicase and pegloticase (contraindicated)
• Methylene blue
• Nitrofurantoin
• Some sulfonamide antibiotics
• Some quinolone antibiotics
• High-dose vitamin C given intravenously

Many common medicines, including acetaminophen (paracetamol) at normal doses, are generally considered safe. Always tell every doctor, dentist and pharmacist that you have G6PD deficiency and check new medicines, including over-the-counter and herbal products. Our practical G6PD deficiency list of foods and medicines to avoid sorts common drugs by risk and covers household products.

Other triggers

• Infections: the most common trigger, including pneumonia, hepatitis and gut infections
• Naphthalene in some mothballs
• Henna applied to babies' skin
• Diabetic ketoacidosis

Symptoms

Most of the time there are no symptoms. During a hemolytic episode:

• tiredness and weakness
• pale skin
• jaundice: yellow skin and eyes
• dark urine, from hemoglobin released into the blood
• fast heartbeat and breathlessness
• back or abdominal pain
• enlarged spleen

In newborns

G6PD deficiency is an important cause of newborn jaundice, which can appear in the first days of life and become severe. Very high bilirubin can cause permanent brain damage (kernicterus). Babies with known or suspected G6PD deficiency need close bilirubin monitoring.

Diagnosis

• G6PD enzyme test: a quantitative blood test measures enzyme activity. It can be falsely normal during or shortly after a hemolytic episode, because older deficient cells have been destroyed; repeat testing after about 3 months may be needed.
• During an episode: blood count, reticulocyte count, bilirubin, LDH, haptoglobin and a blood smear showing "bite cells" and Heinz bodies.
• Genetic testing identifies the variant, especially in females.
• Newborn screening is done in some countries and some US states.

Treatment

• Stop or avoid the trigger and treat any infection.
• Fluids to protect the kidneys.
• Blood transfusion for severe anemia.
• Phototherapy or, rarely, exchange transfusion for newborn jaundice.
• Folic acid may be recommended for people with chronic hemolysis.
• Splenectomy is rarely needed.

Most people recover fully from an episode within weeks once the trigger is removed.

Living with G6PD deficiency

• Carry a list of medicines and foods to avoid, or a medical alert card.
• Check labels and ask pharmacists before taking new medicines.
• Avoid fava beans and mothballs.
• Seek care early for infections and fever.
• Tell your doctor before travel to malaria areas, so safe prevention can be chosen.

Frequently asked questions

What foods should be avoided with G6PD deficiency?

The main food to avoid is fava (broad) beans, which can cause severe hemolysis. Some people are also advised to avoid products containing fava bean flour or derivatives. Most other foods, including other beans and legumes, are generally safe. Ask your doctor about any specific concerns.

What medicines should I avoid with G6PD deficiency?

Medicines that can trigger hemolysis include primaquine, tafenoquine, dapsone, rasburicase, methylene blue, nitrofurantoin and some sulfa and quinolone antibiotics. Always tell doctors and pharmacists about your G6PD deficiency so they can check each new medicine.

Is G6PD deficiency serious?

Usually not. Most people live normal lives and never have symptoms if they avoid triggers. However, triggered hemolysis can be severe, and newborn jaundice from G6PD deficiency can be dangerous if not monitored and treated.

Can women have G6PD deficiency?

Yes. Because the gene is on the X chromosome, men are affected more often, but women can have low enzyme levels, especially if they inherit two affected genes. Women with one affected gene may have mild deficiency and can still have hemolysis with strong triggers.

What is favism?

Favism is sudden hemolytic anemia triggered by eating fava beans in people with G6PD deficiency. It causes paleness, jaundice, dark urine and tiredness, usually within a day or two. It can be serious, especially in children, and may need a blood transfusion.