Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) is an inherited metabolic disorder. The disease is caused by a defect in the G6PD gene, resulting in a glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency. Metabolism refers to all the chemical reactions in the body to convert or use energy. These reactions take place throughout the whole body. In the setting of an enzyme deficiency, metabolism is impaired. G6PD is a protein located on the cell membrane of the red blood cells (erythrocytes) and protects the red blood cell against harmful influences of superoxide and hydrogen peroxide. In people with G6PD deficiency the red blood cells lose their structure and function, resulting in increased sensitivity of these cells for oxidative damage. The red blood cells are then degraded faster than normal and anemia can occur. Most of the time, patients with G6PD deficiency have no symptoms. Therefore, it is better to talk about an enzyme defect rather than a metabolic disease. Sometimes G6PD deficiency is called favism, a haemolytic response to the consumption of fava beans, because all individuals with favism show G6PD deficiency.
G6PDD is the most common enzyme defect worldwide. It was estimated that there are 400 million people with this enzyme deficiency. In 10 to 20% of people from Central Africa, countries surrounding the Mediterranean Sea, the Middle East and the Far East G6PD deficiency is found. The enzyme defect has an additional effect, namely that people with this defect are resistant to malaria. As a consequence, the incidence of G6PD deficiency is high in African and Asian countries. How many people in the Netherlands are affected is unknown.
The two most common forms of G6PD deficiency mostly affect men of African origin (G6PD-A(-)), or men from countries surrounding the Mediterranean Sea (G6PD-Mediterraenan).
The signs and symptoms of G6PD deficiency may vary from one person to the next. G6PD is categorised clinically by the severity of the anaemia the patient experiences, with some patients only showing mild symptoms, whilst others have severe symptoms which may require hospital admission. G6PD deficiency can come to light right after birth. These patients have chronic anemia and jaundice as a result of concomitant problems with the excretion of bilirubin, a degradation product of hemoglobin. The latter is associated with Gilbert’s syndrome in adults.
Some G6PDD patients only occasionally or even never experience anaemia, only in periods of physical stress such as shortly after birth, with fever, infection or after the use of medication. This is referred to as acute anaemia.
The most common symptoms are associated with anaemia:
Between episodes of haemolysis most patients have normal complete blood count.
G6PD deficiency is caused by a defective gene coding for the enzyme glucose-6-phosphate dehydrogenase. G6PD deficiency is an X-linked recessive disorder; the G6PD gene is located on the X chromosome. Therefore, patients with symptoms are almost exclusively males. Men with one affected X-chromosome are always affected, while women have two copies of the X chromosome. In men with G6PD deficiency, the G6PD activity can be slightly diminished or totally absent.
Because women have two copies of the X chromosome, they normally do not show symptoms when one X chromosome is affected. In this case she is carrier of the disease and can pass it on to her offspring. The G6PD activity is normal in carriers. X-inactivation, also called lyonisation, is a process by which one of the copies of the X chromosome is inactivated. When this happens, carriers can have symptoms of the disease. Even more rare is a woman with two affected X chromosomes. Her clinical picture is the same as in men with the disorder.
The diagnosis can be made based on the activity of the enzyme glucose-6-phosphate dehydrogenase in red blood cells. During haemolytic periods, the G6PD activity can be misleadingly high due to the higher enzyme concentration in reticulocytes (immature red blood cells). Their levels are comparatively high in the blood in response to the destruction of mature red blood cells. A defective G6PD enzyme can easily be detected by laboratory research on the red blood cells.
The diagnosis is based on the following tests and research:
There is no medicinal cure for G6PD deficiency. Treatment of this disorder consists of prevention of haemolysis by avoiding oxidising agents, chemicals and other substances, such as:
Furthermore, supportive measures are required for neonatal jaundice and hemolytic episodes:
Top
