OVERVIEW

What is G6PD deficiency?

G6PD deficiency, also known as glucose-6-phosphate dehydrogenase deficiency, is a condition where red blood cells break down and malfunction due to a lack of the enzyme glucose-6-phosphate dehydrogenase.

Most people show no symptoms and may not even know they have G6PD deficiency. However, some individuals may develop clinical symptoms when exposed to certain foods, medications, or chemicals. These symptoms include jaundice, pale skin, dark urine, back or abdominal pain, and anemia.

G6PD deficiency is an inherited condition caused by a genetic mutation and is present from birth. It is more common in certain populations, such as those with ancestors from Africa, the Mediterranean region, parts of Asia, South America, or the Middle East.

Treatment depends on the severity of symptoms and anemia. Most patients only need to avoid specific foods, medications, and chemicals, while severe cases may require blood transfusions.

Is G6PD deficiency common?

Globally, around 400 million people are affected by G6PD deficiency, primarily in tropical, subtropical, and Mediterranean regions.

In China, G6PD deficiency is more prevalent in provinces south of the Yellow River, especially in Yunnan, Guangdong, Guangxi, Hainan, Sichuan, and Guizhou, while it is rare in northern regions. Males are more commonly affected than females.

Are G6PD deficiency and favism the same condition?

No.

Most patients with favism have G6PD deficiency and are sensitive to fava beans. However, G6PD deficiency also includes other conditions such as acute hemolytic anemia, congenital nonspherocytic hemolytic anemia, and neonatal hyperbilirubinemia.

These conditions can be triggered by medications or other substances, and only a small proportion of G6PD-deficient individuals are sensitive to fava beans.

What are the types of G6PD deficiency?

The World Health Organization classifies G6PD deficiency based on enzyme deficiency severity and hemolytic risk:

• Class I: Severe enzyme deficiency (<10% of normal activity), including congenital nonspherocytic hemolytic anemia and severe neonatal hyperbilirubinemia, with lifelong hemolysis even without infection or medication. Anemia and jaundice are often detected in newborns, and hyperbilirubinemia may require exchange transfusion.

• Class II: Severe enzyme deficiency (e.g., Mediterranean G6PD deficiency), usually causing intermittent acute hemolysis triggered by infections, drugs, or chemicals.

• Class III: Moderate enzyme deficiency (10%–60% of normal activity), such as G6PD A-, leading to intermittent acute hemolysis triggered by infections, drugs, or chemicals.

• Class IV: No enzyme deficiency or hemolysis (clinically insignificant).

• Class V: Increased enzyme activity (clinically insignificant).

SYMPTOMS

What are the common manifestations of G6PD deficiency?

The clinical manifestations of G6PD deficiency vary from person to person.

Most patients are asymptomatic, just like normal individuals, and require no treatment. Symptoms only appear after exposure to certain triggers that induce hemolysis. Newborns may sometimes develop jaundice. Some patients may experience persistent hemolysis regardless of the foods they eat or medications they use.

Symptoms of G6PD deficiency may include:

• Jaundice, characterized by yellowing of the skin or whites of the eyes (sclera).
• Pale skin, or pallor in the lips, tongue, or inner eyelids.
• Dark-colored urine.
• Back or abdominal pain.
• Fatigue, weakness, or headaches due to anemia.

What are the manifestations of moderate G6PD deficiency?

Moderate G6PD deficiency presents as acute hemolysis, where the condition is usually stable without anemia or symptoms.

However, 2–4 days after taking certain medications, sudden symptoms such as jaundice, pallor, and dark urine may appear, with or without abdominal or back pain, accompanied by a rapid drop in hemoglobin levels by 3–4 g/dL.

What are the manifestations of severe G6PD deficiency?

Severe G6PD deficiency, also known as Class I G6PD deficiency, typically involves chronic hemolysis. Patients are highly sensitive to drugs and chemicals, and their hemolysis may worsen even when these substances are safe for individuals with Class II or III G6PD deficiency.

Are G6PD deficiency and favism the same condition? What are the symptoms of favism?

Symptoms of favism appear 5–24 hours after consuming fava beans (fresh, fried, or processed fava products; currently, bitter melon is also considered a potential trigger). These symptoms include headache, nausea, back pain, chills, fever, followed by hemoglobinuria and jaundice.

How do drugs and chemicals cause hemolysis in G6PD-deficient patients?

These drugs and chemicals share the common feature of interacting with hemoglobin and oxygen, leading to the formation of hydrogen peroxide (H₂O₂) and other oxidative free radicals within cells.

If G6PD levels are sufficient, they protect cells from oxidation. However, in G6PD deficiency, the accumulation of these oxidants causes hemoglobin and other proteins to oxidize, resulting in loss of protein function and red blood cell death.

How does G6PD deficiency develop?

G6PD (glucose-6-phosphate dehydrogenase) is a protein (enzyme) in red blood cells that stabilizes them and ensures their proper function.

In G6PD-deficient patients, red blood cells contain lower or significantly reduced levels of G6PD, making them more sensitive to certain foods, drugs, and chemicals. Exposure to these triggers can cause red blood cells to rupture and lyse, leading to "hemolysis."

When hemoglobin is released from ruptured red blood cells, the liver becomes overloaded, resulting in excessive bilirubin and jaundice. The body also develops anemia due to the shortage of red blood cells.

If jaundice worsens persistently in a newborn with G6PD deficiency, what impact could it have on the baby?

Acute hemolysis produces excessive bilirubin, which can enter the newborn's brain and cause permanent damage, such as intellectual impairment, hearing loss, and motor dysfunction. Early detection and treatment are crucial.

What serious complications can G6PD deficiency cause?

G6PD-deficient patients may experience acute hemolytic reactions. In severe cases, this can lead to rapid breathing, heart failure, acute kidney failure, or even life-threatening shock.

CAUSES

What are the common causes of G6PD deficiency?

Most individuals with G6PD deficiency do not always experience hemolysis; it typically occurs only when triggered by certain factors. Common triggers include:

• Certain infections: Such as Salmonella, E. coli, beta-hemolytic streptococcus, Rickettsia, and viral hepatitis. In viral hepatitis, liver damage impairs bilirubin processing, leading to significantly elevated serum bilirubin levels.

• Certain medications: Such as sulfonamide antibiotics, antimalarial drugs like primaquine, nitrofurantoin, and gentian violet (a topical antiseptic).

• Certain foods: Such as fava beans and bitter melon. Notably, breastfed infants with G6PD deficiency may develop favism if their mothers consume fava beans.

• Chemical substances: Including naphthalene (found in mothballs), aniline dyes, and henna used in hair dyeing and tattoos.

• Certain diseases: Diabetic ketoacidosis may trigger G6PD deficiency.

Is G6PD deficiency hereditary?

G6PD deficiency is a genetic disorder. The gene responsible is located on the X chromosome, which determines sex. Females have XX chromosomes, while males have XY.

Since males have only one X chromosome, a mutation in this gene results in G6PD-deficient red blood cells, making them G6PD-deficient patients.

If a female has a mutation on one of her X chromosomes, she becomes a carrier of G6PD deficiency. Her other normal X chromosome provides sufficient G6PD to protect red blood cells, preventing symptoms.

In this case, the carrier has a 50% chance of passing the mutated gene to her offspring. She has a 50% probability of having a son with G6PD deficiency, and each daughter has a 50% chance of becoming a carrier.

DIAGNOSIS

How is G6PD deficiency diagnosed?

G6PD activity testing and genetic testing are the primary methods for diagnosing G6PD deficiency.

For patients experiencing acute hemolysis, laboratory tests such as complete blood count, reticulocyte count, serum bilirubin, and free hemoglobin levels are useful indicators for monitoring disease progression.

How is G6PD deficiency diagnosed in newborns?

Newborns can be screened using umbilical cord blood to measure G6PD activity levels.

Which diseases can G6PD deficiency be confused with? How to differentiate them?

Since G6PD deficiency can cause jaundice, it may be confused with other conditions that lead to jaundice. Doctors need to perform G6PD activity testing and genetic testing to distinguish it.

TREATMENT

Which department should I visit for G6PD deficiency?

Hematology, Neonatology, Pediatrics.

Can G6PD deficiency resolve on its own?

G6PD deficiency is a congenital condition and cannot resolve on its own. However, most patients can live normally like healthy individuals as long as they avoid triggers that cause hemolysis.

How is G6PD deficiency treated?

The treatment for G6PD deficiency depends on the patient's symptoms and the severity of anemia. Most patients only need to know which foods, medications, and chemicals to avoid.

• If symptoms occur due to medication or food, discontinue the drug or avoid the food. Generally, patients should avoid foods, drugs, and chemicals that commonly trigger symptoms, such as fava beans, which can induce hemolysis in many patients.

• Patients with severe anemia may sometimes require blood transfusion therapy, where donated blood is administered through a thin tube into a vein. Patients with severe hemolysis may also need intravenous fluids.

• Infants with jaundice are often treated with "phototherapy" or "blue light therapy." During phototherapy, medical staff place the baby under special blue light or wrap them in a "light blanket," which helps the baby's body eliminate harmful components from damaged red blood cells.

• Patients with chronic anemia may require treatment with a vitamin called "folic acid," though this is uncommon.

Does G6PD deficiency require hospitalization?

During acute hemolysis, blood transfusion is the most effective treatment, so such patients require hospitalization.

When should a G6PD deficiency patient seek immediate medical attention?

Acute hemolysis occurs when a large number of red blood cells are destroyed and broken down in a short period.

In this case, red blood cells are lost faster than the body can produce new ones, leading to acute or severe anemia. Symptoms include: pale complexion; yellowing of the skin and whites of the eyes; dark tea-colored urine; fatigue; difficulty breathing; rapid heartbeat. Immediate medical attention is needed if these symptoms occur.

DIET & LIFESTYLE

What should patients with G6PD deficiency pay attention to in their diet?

• Since certain foods, such as fava beans and their products, can trigger or worsen hemolysis in G6PD-deficient patients, they should be avoided. Additionally, patients should be cautious of foods that may cause severe allergic reactions to prevent further complications and disease progression.

• Consume safe, familiar foods and supplement the diet with easily digestible, nutrient-rich foods high in protein, calories, and vitamins.

• Mothers breastfeeding infants with G6PD deficiency should ensure sufficient milk supply while avoiding certain foods or medications that may worsen hemolysis in the baby through breastmilk.

What should patients with G6PD deficiency pay attention to in daily life?

• Avoid taking or coming into contact with oxidizing drugs and chemicals.

• For infants with G6PD deficiency, breastfeeding mothers should also avoid consuming substances that may trigger hemolysis to prevent the baby from absorbing them through breastmilk.

Does G6PD deficiency require follow-up tests? How?

Patients with G6PD deficiency do not need regular blood tests or follow-up visits as long as they avoid triggers such as certain foods and chemicals throughout their lives.

Does G6PD deficiency affect fertility?

Patients with G6PD deficiency can have children. It is recommended to conduct newborn screening to determine whether the baby has G6PD deficiency, enabling early intervention for neonatal jaundice caused by the condition and preventing prolonged illness due to improper treatment, which could affect the child's quality of life.

Since most G6PD-deficient patients are asymptomatic, many are unaware of their condition. Individuals from Yunnan, Guangdong, Guangxi, Hainan, Sichuan, and Guizhou are advised to undergo G6PD deficiency screening during pregnancy planning.

PREVENTION

Can G6PD deficiency be prevented? How to prevent it?

G6PD deficiency can be prevented to some extent. Most patients can live as healthily as ordinary people as long as they avoid foods, medications, or chemicals that may trigger hemolysis for life.

Which medications or foods are unsafe for G6PD deficiency patients?

• Unsafe medications: Primaquine, nitrofurantoin, chloramphenicol, dapsone, furazolidone, phenazopyridine, methylene blue, probenecid, salicylic acid, sulfamethazine, sulfamethoxazole, sulfasalazine, gliclazide, glipizide, hydroxychloroquine, etc.

• Chinese herbs to avoid: Cow bezoar, honeysuckle, wintersweet flower, coptis, pearl powder.

• Foods to avoid: Fava beans and their products (e.g., vermicelli containing fava beans), all legumes, blueberries (including blueberry yogurt), soy products, bitter melon, etc.

• Others: Naphthalene-containing mothballs or insect repellents, aniline dyes, and henna ingredients used in hair dyes and tattoos.

• For people with G6PD deficiency, the following medications commonly used to treat glaucoma, such as brinzolamide and acetazolamide, are prohibited.

Not all the above foods and medications must be strictly avoided, as it depends on the severity of the patient's G6PD deficiency and the dosage of the chemical agents involved.