Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited (genetic) condition that affects red blood cells. Red blood cells carry oxygen throughout your body. In babies with G6PD deficiency, red blood cells break down too quickly.

G6PD is an enzyme that helps protect red blood cells from reactive oxygen species, which can be harmful when they build up. Reactive oxygen species are normal products of the body’s processes, but at high levels, they can cause damage to red blood cells.

Normally, red blood cells break down slowly enough for the body to continuously replace them. Babies with G6PD deficiency have red blood cells that break down faster than they can be replaced, so red blood cell levels are low. This means that babies with G6PD deficiency have a harder time bringing oxygen to the body, causing the signs and symptoms of the condition.

G6PD deficiency affects about 1 in 10 African American males in the United States.

Normal Function

The G6PD gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase. This enzyme, which is active in virtually all types of cells, is involved in the normal processing of carbohydrates. It plays a critical role in red blood cells, which carry oxygen from the lungs to tissues throughout the body. This enzyme helps protect red blood cells from damage and premature destruction.

Glucose-6-phosphate dehydrogenase is responsible for the first step in the pentose phosphate pathway, a series of chemical reactions that convert glucose (a type of sugar found in most carbohydrates) to another sugar, ribose-5-phosphate. Ribose-5-phosphate is an important component of nucleotides, which are the building blocks of DNA and its chemical cousin RNA. This chemical reaction produces a molecule called NADPH, which plays a role in protecting cells from potentially harmful molecules called reactive oxygen species. These molecules are byproducts of normal cellular functions. Reactions involving NADPH produce compounds that prevent reactive oxygen species from building up to toxic levels within cells. The production of NADPH by glucose-6-phosphate dehydrogenase is essential in red blood cells, which are particularly susceptible to damage by reactive oxygen species because they lack other NADPH-producing enzymes.

Health Conditions Related to Genetic Changes

Glucose-6-phosphate dehydrogenase deficiency

More than 200 variants (also called mutations) that cause glucose-6-phosphate dehydrogenase deficiency have been identified in the G6PD gene. Almost all of these variants lead to changes in single building blocks (amino acids) in the glucose-6-phosphate dehydrogenase enzyme. These changes disrupt the normal structure and function of the enzyme or reduce the amount of the enzyme produced in cells.

Without enough functional glucose-6-phosphate dehydrogenase, red blood cells are unable to protect themselves from the damaging effects of reactive oxygen species. The damaged cells are likely to rupture and break down prematurely (undergo hemolysis). Factors such as infections, certain drugs, and ingesting fava beans can increase the levels of reactive oxygen species, causing red blood cells to undergo hemolysis faster than the body can replace them. This loss of red blood cells causes the signs and symptoms of hemolytic anemia, which is a characteristic feature of glucose-6-phosphate dehydrogenase deficiency.

Other Names for This Gene

• G6PD1
• G6PD_HUMAN

Genomic Location

• Each son has a 50% chance to be unaffected, and a 50% chance to be affected
• Each daughter has a 50% chance to be unaffected, and a 50% chance to be a carrier

Newborn screening for G6PD deficiency requires collecting a small amount of blood from your baby’s heel. Screening measures how much G6PD enzyme is in your baby’s blood. This enzyme is responsible for protecting red blood cells. Babies with a low level of this enzyme might have G6PD deficiency.

In some cases, a screening test may also look for changes in the gene that causes G6PD deficiency (called G6PD). Babies with a change in the G6PD gene may have G6PD deficiency.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for G6PD is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result usually means that your baby has the condition and that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood tests
• Genetic testing using a blood sample

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition are rare. However, screening samples that are collected after a baby receives red blood cells from someone else (a red cell transfusion) will be inaccurate.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.

It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.

Treatments may include the following:

• Phototherapy to help with jaundice
• Blood transfusions in some cases
• Avoidance of fava beans or drugs that trigger anemia

Children with symptoms who receive early health care and treatment for G6PD deficiency can have healthier lives than those who do not receive treatment.