Glucose-6-phosphate dehydrogenase deficiency

Alternat names

G6PD deficiency; Hemolytic anemia due to G6PD deficiency

Definition

Glucose 6 phosphate dehydrogenase (G6PD) deficiency is a hereditary condition in which red blood cells break down (hemolysis) when the body is exposed to certain foods, drugs, infections or stress. It occurs when a person is missing or has low levels of the enzyme glucose-6-phosphate dehydrogenase. This enzyme helps red blood cells work properly.

Cause

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by mutations in the G6PD gene.
• This gene gives the body instructions to make an enzyme called G6PD, which is involved in processing carbohydrates.
• This enzyme also protects red blood cells from potentially harmful molecules called reactive oxygen species.
• Chemical reactions involving G6PD produce compounds that prevent reactive oxygen species from building up to toxic levels within red blood cells.

Gene mutations

• Mutations in the G6PD gene lower the amount of G6PD or alter its structure, lessening its ability to play its protective role.
• As a result, reactive oxygen species can accumulate and damage red blood cells.
• Factors such as infections, certain drugs, or eating fava beans can increase the levels of reactive oxygen species, causing red blood cells to be destroyed faster than the body can replace them.
• This reduction of red blood cells causes the signs and symptoms of hemolytic anemia in people with G6PD deficiency.

Inheritance

X-linked recessive inheritance

G6PD deficiency is inherited in an X-linked recessive manner.

• X-linked recessive conditions are much more common in males, who have only one X chromosome (and one Y chromosome).
• Females have two X chromosomes, so if they have a mutation on one of them, they still have one X chromosome without the mutation. Females with one X chromosome mutation are known as carriers and are usually unaffected. However, females can be affected if they have a mutation in both copies of the G6PD gene, or in some cases, if they have only one mutation. Females with one mutation may have lower G6PD activity than would normally be expected due to a phenomenon called skewed lyonization.

If a mother is a carrier of an X-linked recessive condition and the father is not, the risk to each child depends on whether the child is male or female.

• 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
• If a father has the condition and the mother is not a carrier, all sons will be unaffected, and all daughters will be carriers.

Signs and symptoms

• People with G6PD deficiency generally do not have symptoms unless their red blood cells are exposed to certain chemicals in food or medicine, certain bacterial or viral infections, or to stress.
• Many people with this condition never experience symptoms.
• The most common medical problem associated with G6PD deficiency is hemolytic anemia, which occurs when red blood cells are destroyed faster than the body can replace them.
• This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, enlarged spleen, and a rapid heart rate.
• Some patients have a history of chronic hemolytic anemia.
• Skin ulcers are uncommon but may occur in people with severe G6PD deficiency.
• Because G6PD deficiency is inherited in an X-linked recessive manner, it is more common for males to have symptoms.
• This is because males have only one copy of the G6PD gene.
• If this one copy has a mutation, they will definitely have G6PD deficiency.
• However, while females have two copies of the G6PD gene, some females are as severely affected as males.
• This can be the case in females who have a mutation in both copies of the G6PD gene, or even in females who have only one mutation.
• Females with one mutation may have lower G6PD activity than would normally be expected due to a phenomenon called skewed lyonization.

Diagnosis

A blood test can be done to check the level of G6PD.

Other tests that may be done include:

• Bilirubin level
• Complete blood count
• Hemoglobin - urine
• Haptoglobin level
• LDH test
• Methemoglobin reduction test

Treatment

• The most important aspect of management for G6PD deficiency is to avoid agents that might trigger an attack.
• In cases of acute hemolytic anemia, a blood transfusion or even an exchange transfusion may be required.

NIH genetic and rare disease info

• NIH info on Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase deficiency is a rare disease.

Glucose-6-phosphate dehydrogenase deficiency Resources
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