Дефицит глюкозо-6-фосфатдегидрогеназы: причины, проявления и лечение.

Treatment of acute episodes may include medications for infection, stopping the offending medication, or blood transfusions. It is particularly common in certain parts of Africa, Asia, the Mediterranean, and the Middle East.

G6PD deficiency results from mutations in the G6PD gene. G6PD gene contributes to the production of glucose 6 phosphate dehydrogenase. Chemical reactions involving glucose 6 phosphate dehydrogenase produce compounds that prevent reactive oxygen species from building up to toxic levels within red blood cells. If reduction in the amount of glucose 6 phosphate dehydrogenase or alteration of structure occurs due to the mutations of G6PD gene, the enzyme loses its protective role and leads to the accumulation of reactive oxygen species and thus damage of red blood cells. Stress from a bacterial or viral infection. 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 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. High dose intravenous vitamin C has also been known to cause haemolysis in G6PD deficiency carriers; therefore, G6PD deficiency testing is routine before infusion of doses of 25 g or more.

Two variants (G6PD A− and G6PD Mediterranean) are the most common in human populations. G6PD A− has an occurrence of 10% of Africans and African Americans while G6PD Mediterranean is prevalent in the Middle East. The known distribution of the mutated allele is largely limited to people of Mediterranean origins (Spaniards, Italians, Greeks, Armenians, Sephardi Jews and other Semitic peoples). Both variants are believed to stem from a strongly protective effect against Plasmodium falciparum and Plasmodium vivax malaria. It is particularly frequent in the Kurdish Jewish population, wherein approximately 1 in 2 males have the condition and the same rate of females are carriers. All mutations that cause G6PD deficiency are found on the long arm of the X chromosome, on band Xq28. The G6PD gene spans some 18.5 kilobases. The G6PD / NADPH pathway is the only source of reduced glutathione in red blood cells (erythrocytes). The role of red cells as oxygen carriers puts them at substantial risk of damage from oxidizing free radicals except for the protective effect of G6PD/NADPH/glutathione. When all remaining reduced glutathione is consumed, enzymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to cross bonding and protein deposition in the red cell membranes. Damaged red cells are phagocytosed and sequestered (taken out of circulation) in the spleen. The hemoglobin is metabolized to bilirubin (causing jaundice at high concentrations). The red cells rarely disintegrate in the circulation, so hemoglobin is rarely excreted directly by the kidney, but this can occur in severe cases, causing acute kidney injury. Deficiency of G6PD in the alternative pathway causes the buildup of glucose and thus there is an increase of advanced glycation endproducts (AGE). The deficiency also reduces the amount of NADPH, which is required for the formation of nitric oxide (NO). The high prevalence of diabetes mellitus type 2 and hypertension in Afro Caribbeans in the West could be directly related to the incidence of G6PD deficiency in those populations. Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome – see Skewed X inactivation), homozygous females have been described; in these females there is co incidence of a rare immune disorder termed chronic granulomatous disease (CGD).

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 person.

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e. g. hepatitis A and hepatitis B) may prevent infection induced attacks. In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation. Those affected should avoid drugs such as aspirin. Some patients may benefit from removal of the spleen (splenectomy), as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency. AG1, a recently discovered small molecule, has been shown to increase the activity of the G6PD enzyme in the three common variants of the deficiency. Due to the absence of medications to treat G6PD, AG1 is a promising precursor in developing a pharmacological treatment effective for multiple G6PD enzymopathies.

G6PD deficient individuals do not appear to acquire any illnesses more frequently than other people, and may have less risk than other people for acquiring ischemic heart disease and cerebrovascular disease. However, a recent study revealed that G6PD deficiency increases the cardiovascular risk up to 70%. The risk conferred by G6PD deficiency is moderate compared with the impact of primary cardiovascular risk factors. Besides, a published review hypothesized that G6PD deficiency could reduce the antiplatelet efficacy of clopidogrel (clopidogrel resistance).

G6PD deficiency is the second most common human enzyme defect after ALDH2 deficiency, being present in more than 400 million people worldwide. G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990. The Mediterranean Basin is where favism is most common, especially among Mizrahi Jews, Sardinians, Cypriots, Greeks, Egyptians and some African populations, including those who have these ancestries. Favism has also been documented outside of the Mediterranean basin, in other Middle Eastern and East Asian nations like Iraq, Iran, Bulgaria and China. Sardinia has the highest reported frequency of favism, with five instances per every 1,000 people. in particular the form of malaria caused by Plasmodium falciparum, the most deadly form of malaria. A similar relationship exists between malaria and sickle cell disease. One theory to explain this is that cells infected with the Plasmodium parasite are cleared more rapidly by the spleen. This phenomenon might give G6PD deficiency carriers an evolutionary advantage by increasing their fitness in malarial endemic environments. In vitro studies have shown that the Plasmodium falciparum is very sensitive to oxidative damage. This is the basis for another theory, that is that the genetic defect confers resistance due to the fact that the G6PD deficient host has a higher level of oxidative agents that, while generally tolerable by the host, are deadly to the parasite.

The modern understanding of the condition began with the analysis of patients who exhibited sensitivity to primaquine. The discovery of G6PD deficiency relied heavily upon the testing of prisoner volunteers at Illinois State Penitentiary, a type of study which today is considered unethical and cannot be performed. When some prisoners were given the drug primaquine, some developed hemolytic anemia but others did not. In spite of these results, the US military administered the drug widely during the Korean War to prevent the relapsing infection caused by Plasmodium vivax hypnozoites. Numerous cases of hemolytic anemia were observed in US soldiers of North African and Mediterranean descent. After studying the mechanism through Cr51 testing, it was conclusively shown that the hemolytic effect of primaquine was due to an intrinsic defect of erythrocytes.

In both legend and mythology, favism has been known since antiquity. The priests of various Greco Roman era cults were forbidden to eat or even mention beans, and Pythagoras had a strict rule that to join the society of the Pythagoreans one had to swear off beans. This ban was supposedly because beans resembled male genitalia, but it is possible that this was because of a belief that beans and humans were created from the same material.