Hereditary hemolytic anemia caused by deficient activity of glucose-6- phosphate dehydrogenase erythrocyte

August 12, 2017 17:51 | Genetic Diseases

deficiency of glucose-6-phosphate dehydrogenase (G-6-PD) - the most common hereditary anomaly of red blood cells, leading to hemolytic crisis (worsening as a result of intensive destruction of red blood cells), associated with taking a number of medications.Beyond crisis (acute) health and condition of the person with the disease is fully compensated.It is known that a number of drugs, especially anti-malarial agents may cause some individuals acute hemolytic anemia.Intolerance of medications is often observed in families.It is found that after the hemolytic crisis in people erythrocytes appear coarse inclusions, which are called Heinz bodies.After placing the red blood cells of persons with acute hemolytic crisis caused by taking any medications, in a test tube with substance atsetilfenilgidrazin in red blood cells there is a lot of Heinz bodies (much more than in healthy people).The first description of the activity of the enzyme deficiency of G-6-PD refers to the 1956 low enzyme activity was found in

patients treated with prophylactic antimalarial drug primaquine.At the same time he developed an acute hemolytic crisis.Regardless of these studies, other scientists in 1957 discovered a deficiency of this enzyme in the red blood cells of a young man from Iran, which has been periodically hemolytic crisis without receiving any medication.

Dispatched deficiency of this enzyme activity is always the clutch with the X chromosome.Clutch mutant gene with the floor gives a significant predominance of men among persons with the disease.It manifests itself in men who have inherited this pathology of the mother with her X chromosome, women have inherited the disease from both parents, and in some women who have inherited the disease from a parent.

most common deficiency of G-6-PD is found in Europe, located on the Mediterranean coast - in Greece, in Italy.Widespread deficiency of enzyme activity in some countries of Latin America and Africa.

In our country, a deficit of activity of G-6-PD distributed unevenly.The high concentration of the abnormal gene is found in Azerbaijan, among the various peoples of Dagestan, Uzbekistan, Armenia and Georgia.Perhaps the high accumulation of the abnormal gene in these localities contributes to extant custom of consanguineous marriages.This leads to the accumulation of a population of women with two mutant X-chromosome in which the decay of erythrocytes after administration drug manifested heavier than the carriers one mutant X-chromosome.In addition, it increases the probability of the birth of mutant males with X-linked tion.This also contributed to the widespread in the past in these areas of tropical malaria.There is a hypothesis that a deficiency of G-6-PD offers some advantages in the fight against tropical malaria, and persons with a deficiency, rarely die of the disease.In favor of this hypothesis is the unequal distribution of the parasite among the red blood cells heterozygous women: in normal cells, the parasite is much more than in the pathologically changed.

first stage the drug metabolism in the body is in its transition to an active form, which can cause changes in the structure of the erythrocyte membrane.The active form of the drug reacts with hemoglobin.This creates a certain amount of hydrogen peroxide.In healthy people, acute hemolytic crisis developed with the introduction of significant amounts of the drug (toxic dose).The crisis may occur when System Restore is unable to cope with an excess of hydrogen peroxide, resulting in red blood cells.At the same time there are bull Heinz in red blood cells.The spleen releases these cells from erythrocytes, and the lost portion of the surface of erythrocytes that leads to their premature death.

WHO experts divided enzyme deficiency variants of G-6-PD into 4 classes according to the level and manifestations occurring enzyme activity in the erythrocytes.

1st class - versions, which are accompanied by chronic hemolytic anemia.

2nd class - options with the level of enzyme activity in the erythrocytes 0-10% of normal, carrier which causes the absence of hemolytic anemia without exacerbation and aggravation associated with taking drugs or ingestion of faba bean.

3rd class - options with the level of enzyme activity in erythrocytes 10-60% of normal at which light can be symptoms of hemolytic anemia associated with drug intake.

4th class - versions with normal or near normal level of enzyme activity without any symptoms.

Hemolytic anemia at birth is at deficiency of the enzyme G-6-PD as the 1st and 2nd class.The activity of G-6-PD in red blood cells do not always correspond to the severity of symptoms of the disease occur.In many embodiments of the 1st class is determined by 20-30% -s' enzyme activity, and with zero activity in certain media does not appear to be any symptoms of the disease.This is due, firstly, to the properties of the mutant enzymes themselves, and secondly, with a neutralization rate of drugs in the liver.

The most common activity of the enzyme deficiency of G-6-PD makes no manifestation without provocation.In most cases, hemolytic crises begin after taking certain medications, especially sulfa drugs (norsulfazol, streptocid, sulfadimetoksin, sulfacetamide sodium, etazol, Biseptol), anti-malarial drugs (primaquine, quinine, quinacrine), nitrofuran derivatives (furazalidon, furadonin, furagin,5-NOC, blacks, nevigramon), drugs to treat tuberculosis (tubazid, ftivazid) niridazole anthelmintic drug (ambilhar).At deficiency of the enzyme activity of G-6-PD can be used antimalarial delagil and of sulfa drugs - only ftalazol.Some drugs in larger doses cause hemolytic crises, and small can be used in deficiency of the enzyme activity of G-6-PD.These drugs include acetylsalicylic acid (aspirin), aminopyrine, phenacetin, chloramphenicol, streptomycin, Arta, antidiabetic sulfa drugs.

manifestations of the disease may occur in the 2-3 th day from the start of drug administration.First, there is a slight yellow coloring of eyes, urine becomes dark.If at this time to stop taking medication, severe hemolytic crisis does not develop, otherwise, on the 4th or 5th day may be hemolytic crisis with the release of black urine, sometimes brown, the color that is associated with the collapse of red blood cells within the blood vessels.The hemoglobin content in this period may be reduced to 20-30 g / l and more.In severe cases the temperature rises, there is a sharp headache, pain in the limbs, vomiting, and sometimes diarrhea.There is shortness of breath, decreased blood pressure.Often increases spleen, sometimes liver.

In rare cases a massive disintegration of red blood cells triggers intravascular coagulation of blood to form clots that close the lumen of blood vessels.This, in turn, may impair circulation to the kidneys, and acute renal failure.

the study of blood revealed anemia with an increase in the number of immature red blood cells (reticulocytes).The number of white blood cells.Sometimes, especially in children, the number of leukocytes can be very large (100 x 109 / l and above).Platelets normally do not change.In a special study of red blood cells during the severe exacerbation of the disease reveal a large number of Heinz bodies.As a result of the destruction of red blood cells express the content of free hemoglobin increases in serum bilirubin is often increased.The urine also appears hemoglobin.

Children often develop severe hemolytic crises than in adults.In marked deficiency of the enzyme activity of G-6-PD Hemolytic crises sometimes occur immediately after birth.This hemolytic disease of the newborn, is not associated with immunological conflict between him and his mother.It can occur just as hard as hemolytic anemia associated with Rhesus incompatibility between mother and child, can provoke severe jaundice with severe central nervous system.

hemolytic crisis with a deficit of activity of the enzyme G-6-PD sometimes occur in infectious diseases (influenza, salmonella, hepatitis), regardless of the drug, can be provoked exacerbation of diabetes mellitus or renal failure development.

A small percentage of people with deficient activity of the enzyme G-6-PD has a constant hemolytic anemia associated with taking drugs.In these cases, there is a slight enlargement of the spleen, hemoglobin decreased not so much more increased levels of bilirubin in the blood.These people may be exacerbated disease after medication or above, or infectious diseases.

Some people with deficiency of G-6-PD develops hemolytic anemia associated with the consumption of horse beans - favism.Manifestations favism signs consist of rapid destruction of red blood cells coming faster than after administration of drugs, and digestion disorders related to a direct effect on faba bean intestine.Hemolytic crises occur within a few hours after eating the beans, at least 1-2 days, their severity depends on the amount eaten beans.Favism often complicated by renal failure.Mortality in favism higher than forms due to drug administration.Inhalation of pollen hemolytic crises are more often light, but there are a few minutes after contact with pollen.

described single hemolytic crises resulting from the reception of the male fern, eating blueberries, blueberry.

basis to detect deficiency of the enzyme G-6-PD is the determination of the enzyme activity by means of special methods of investigation.

Treatment deficiency of the enzyme G-6-PD is necessary only at the expressed signs of acute destruction of red blood cells.At constant hemolytic anemia with a deficit of activity of G-6-PD-1 class sometimes make removal of the spleen.In non-severe hemolytic crisis with a slight darkening of the urine, light yellowish sclera and slow decrease in hemoglobin required the cancellation caused the crisis medication, riboflavin intake to 0,015 g 2-3 times a day, xylitol 5-10 g 3 times a day of vitamin E.

at the expressed symptoms of intravascular collapse of red blood cells, especially when favism, the need for prevention of acute renal failure.Prevention of renal failure is carried out only in a hospital or intensive care unit, depending on the severity of the condition.

Red blood cells are transfused only when pronounced anemia.

prevention of hemolytic crises is reduced to the failure of the drug that can cause exacerbation of the disease.In this case, such drugs must be replaced by analogs, which doctor must do.

forecast .Persons with a deficiency of the enzyme G-6-PD almost healthy, and subject to preventive measures can be healthy throughout life.The efficiency of such people do not suffer.Chronic haemolytic anemia associated with deficiency of G-6-PD, usually non-severe.Typically, performance is fully maintained.The prognosis of acute hemolytic crisis depends on the speed of the abolition of the drug that caused hemolytic crisis, age, state of the cardiovascular system.When favism worse than forecast, but preventive measures do little mortality even in cases complicated by acute renal failure.