The enzyme glucose-6-phosphate dehydrogenase (G6PD) is one of the enzymes of the pentose phosphate pathway. This pathway is involved in keeping an adequate amount of the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) in cells.
NADPH in turn maintains the levels of glutathione which protects the red cell from oxidative damage. G6PD is the rate-limiting enzyme in the pentose phosphate pathway.
Thus, deficiency of the G6PD enzyme results in reduced glutathione making the red cells vulnerable to oxidative damage and thus liable to haemolysis.
Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder that occurs most often in males. This condition mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body.
In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis.
The most common medical problem associated with glucose-6-phosphate dehydrogenase 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, and a rapid heart rate. In people with glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia is most often triggered by bacterial or viral infections or by certain drugs (such as some antibiotics and medications used to treat malaria).
Hemolytic anemia can also occur after eating fava beans or inhaling pollen from fava plants (a reaction called favism).
Glucose-6-dehydrogenase deficiency is also a significant cause of mild to severe jaundice in newborns. Many people with this disorder, however, never experience any signs or symptoms.
- Depends upon the severity of the enzyme deficiency.
- Most are asymptomatic.
- May be a history of neonatal jaundice, severe enough to require exchange transfusion.
- History of drug-induced haemolysis.
- Gallstones are common.
- Most often, examination is unremarkable.
- Pallor of anaemia.
- During a crisis jaundice occurs.
- Back or abdominal pain (usually occurs when >50% haemolysis occurs).
- Splenomegaly may occur.
How common is glucose-6-phosphate dehydrogenase deficiency?
An estimated 400 million people worldwide have glucose-6-phosphate dehydrogenase deficiency. This condition occurs most frequently in certain parts of Africa, Asia, and the Mediterranean. It affects about 1 in 10 African-American males in the United States.
How do people inherit glucose-6-phosphate dehydrogenase deficiency?
This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes.
In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.
In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.
A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Avoidance of substances that may precipitate haemolysis is essential. Usually no further management is required, although if haemolysis is marked there may be benefit from folate supplementation.
Management of acute haemolysis:
- Seek specialised advice.
- Blood transfusions may be needed.
- Dialysis may be required in acute kidney injury.
- Infants – more susceptible to neonatal jaundice, especially if premature, and exchange transfusion may be required.
Management of chronic haemolysis or stable disease:
- Splenectomy may help.
- Supplementation with folic acid.
- Avoidance of precipitating drugs, and broad beans (usually favism occurs in the Mediterranean variety of the disease).
- Avoid naphthalene – found in mothballs.
Complications and prognosis
Most people with G6PD deficiency have a normal life expectancy despite a predisposition to neonatal jaundice and sensitivity to certain drugs. If neonatal jaundice is not energetically treated, there may be a hidden risk for kernicterus.
However, G6PD activity is higher in premature infants born between 29 and 32 weeks of gestation than in term neonates.Even if G6PD deficiency is anticipated, prophylactic oral phenobarbital given to the baby after delivery does not decrease the need for phototherapy or exchange transfusions in G6PD-deficient neonates.
Sn-mesoporphyrin (SnMP) is a potent inhibitor of bilirubin production that is effective in moderating neonatal hyperbilirubinaemia caused by ABO incompatibility, immaturity, and unspecified mechanisms and may also help in G6PD deficiency.
There is no definite association between G6PD deficiency and susceptibility to cataracts.
Although the disease is thought to be fairly benign, where enzyme levels are severely deficient there can be inadequate leukocyte function also.
This results in chronic granulomatous disease. In Saudi Arabia the G6PD status of all children aged 1 month to 14 years, who were treated for meningitis, septicaemia, osteomyelitis, or typhoid fever during a nine-year period, was reviewed.
The observed frequency of G6PD deficiency was significantly higher than expected for the entire group, for females with both catalase-positive and catalase-negative infection, and for males with catalase-positive infections.