Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) also known as favism (after the fava bean) is an X-linked recessive inborn error of metabolism that predisposes to hemolysis (spontaneous destruction of red blood cells) and resultant jaundice in response to a number of triggers, such as certain foods, illness, or medication. It is particularly common in people of Mediterranean and African origin. The condition is characterized by abnormally low levels of glucose-6-phosphate dehydrogenase, an enzyme involved in the pentose phosphate pathway that is especially important in the red blood cell. G6PD deficiency is the most common human enzyme defect. There is no specific treatment, other than avoiding known triggers.
Carriers of the G6PD allele appear to be protected to some extent against malaria, and in some cases affected males have shown complete immunity to the disease. This accounts for the persistence of the allele in certain populations in that it confers a selective advantage. G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990.
Signs and symptoms
Most individuals with G6PD deficiency are asymptomatic.
Symptomatic patients are almost exclusively male, due to the X-linked pattern of inheritance, but female carriers can be clinically affected due to unfavorable lyonization, where random inactivation of an X-chromosome in certain cells creates a population of G6PD-deficient red blood cells coexisting with normal red cells. A typical female with one affected X chromosome will show the deficiency in approximately half of her red blood cells. However, in rare cases, including double X deficiency, the ratio can be much more than half, making the individual almost as sensitive as a male.
Abnormal red blood cell breakdown (hemolysis) in G6PD deficiency can manifest in a number of ways, including the following:
- Prolonged neonatal jaundice, possibly leading to kernicterus (arguably the most serious complication of G6PD deficiency)
- Hemolytic crises in response to:
- Illness (especially infections)
- Certain drugs (see below)
- Certain foods, most notably broad beans
- Certain chemicals
- Diabetic ketoacidosis
- Very severe crises can cause acute kidney failure
Favism may be formally defined as a hemolytic response to the consumption of broad beans. All individuals with favism show G6PD deficiency. However, not all individuals with G6PD deficiency show favism. Favism is known to be more prevalent in infants and children, and G6PD genetic variant can influence chemical sensitivity. Other than this, the specifics of the chemical relationship between favism and G6PD are not well understood.
6-phosphogluconate dehydrogenase (6PGD) deficiency has similar symptoms and is often mistaken for G6PD deficiency, as the affected enzyme is within the same pathway, however these diseases are not linked and can be found within the same patient.
Many substances are potentially harmful to people with G6PD deficiency. Variation in response to these substances makes individual predictions difficult. Antimalarial drugs that can cause acute hemolysis in people with G6PD deficiency include primaquine, pamaquine, and chloroquine. There is evidence that other antimalarials may also exacerbate G6PD deficiency, but only at higher doses. Sulfonamides (such as sulfanilamide, sulfamethoxazole, and mafenide), thiazolesulfone, methylene blue, and naphthalene should also be avoided by people with G6PD deficiency as they antagonize folate synthesis, as should certain analgesics (such as aspirin, phenazopyridine, and acetanilide) and a few non-sulfa antibiotics (nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone). Henna has been known to cause hemolytic crisis in G6PD-deficient infants. Rasburicase is also contraindicated in G6PD deficiency.
Two variants (G6PD A− and G6PD Mediterranean) are the most common in human populations. G6PD A− has an occurrence of 10% of African-Americans while G6PD Mediterranean is prevalent in the Middle East. The known distribution of the disease is largely limited to people of Mediterranean origins (Spaniards, Italians, Greeks, Armenians, and Jews). These variants are believed to stem from a protective effect against Plasmodium falciparum and Plasmodium vivax malaria.
All mutations that cause G6PD deficiency are found on the long arm of the X chromosome, on band Xq28. Read more From Wikipedia, the free encyclopedia