From Big Medical Encyclopedia


(enzyme[s] + Greek penia poverty, shortcoming; anemia) — the group name of preferential hemolitic anemias resulting from hereditary insufficiency of certain enzymes of erythrocytes.

Enzimopenichesky anemia is observed at disturbance of metabolism of glutathione (see) as a result of insufficiency of enzymes of glyukozo-6-fos-veils — dehydrogenases, fosfoglyuko-natdegidrogenaza, lutationsinte-Tazy, and - of a lutama of a ltsisteinsintetaza, a glutationreduktaza, glutathione peroxidases; at disturbance of activity of enzymes of glycolysis (sml — a hexokinase, glucose phosphate-isomerase, fosfofruktokinaza, fruktozobis — phosphate-zymohexase, triozofosfatizo-meraza, phosphoglycerate kinases, pi-ruvatkinaza, phosphoglycerates-phospho-mutases; at disturbance of metabolism of nucleotides (see. Nucleic acids) as a result of hypoactivity of an adenilatkinaza, a pyrimidine - 5 '-nukleotidnukleozida-zy, adenozintrifosfataza and ribo-kinases.

Etiology and pathogeny. E is most widespread. and., caused by insufficiency of glyukozo-6-fos-veils — dehydrogenases in erythrocytes. According to WHO experts (1973), hereditary insufficiency gluco-zo-6-phosphate — dehydrogenases is inherent in, at least, 300 million people belonging to various ethnic groups living preferential in endemic on malaria (in the past or now) zones. A combination of malaria as selective factor and an endogamy (kinship marriages) in the conditions of isolates (see) the fact of extraordinary distribution of persons with deficit glyukozo-6-phosphate — dehydrogenases among nek-ry ethnic groups of the Middle East is caused. In the USSR persons with insufficiency glyukozo-6-phosphate — dehydrogenases in a number of areas of Central Asia and Transcaucasia, especially in Azerbaijan where earlier malaria was widespread are registered. Insufficiency glyukozo-6-phosphate —

dehydrogenases of erythrocytes is inherited on linked to a floor (with X-chromosome) to type. According to it a wedge, manifestations of insufficiency glyukozo-6-phosphate — dehydrogenases are observed preferential at male-gemizigot, i.e. at the men who inherited this pathology from mother with her X-chromosome and at female homozygotes (on abnormal X-chromosome). At female-geterozigo! 1 activity glyukozo-6-phosphate — dehydrogenases of erythrocytes depends on a ratio of normal erythrocytes and erythrocytes with insufficiency of glyukozo-6-fos-veils — dehydrogenases. In a crust, time the St. 250 options of insufficiency glyukozo-6-phosphate — dehydrogenases, including 23 options opened in the USSR are described. Their identification is based on the following criteria: activities of enzyme in a hemolysate, electrophoretic mobility in gel, a constant of Mikhaeli-sa (Kt), heat stability, ability to oxidize 2-dezoksiglyu-kozo-6-phosphate, an optimum of pH. For normal (100%) activity glyukozo-6-phosphate — dehydrogenases accept activity of B+ of option glyukozo-6-phosphate — dehydrogenases (the Mediterranean option). Abnormal options B“ and And" are characterized by hypoactivity (5 — 10%) or lack of activity glyukozo-6-phosphate — dehydrogenases; the Mediterranean option B" differs from the African option A" in wider range of potentially hemolitic agents (pharmaceuticals) provoking hemolysis at persons with insufficiency glyukozo-6-phosphate — dehydrogenases.

According to activity glyukozo-6-phosphate — dehydrogenases in erythrocytes and a wedge, manifestations of a gemizigotny carriage of anomaly, options glyukozo-6-phosphate — dehydrogenases divide into 5 classes. The first class — the options causing chronic hemolitic anemia irrespective of activity of enzyme; the second class — options with activity of enzyme

of 0 — 10% of norm, at to-rykh are observed lekarstvenno the induced crises and a favism (see); the third class — options with activity of enzyme of 10 — 60% of norm, at to-rykh are possible lekarstvenno the induced hemolitic crises; the fourth class — options with activity of enzyme, normal or close to norm (60 — 120%), without wedge, manifestations; the fifth class — options with high activity glyu-kozo-6-phosphate — dehydrogenases. Changes of functional properties of enzyme consider as manifestation of a mutation of the structural gene controlling synthesis glyukozo-6-phosphate — dehydrogenases therefore the abnormal, inactive option of this enzyme is formed. The key role glyukozo-6-phosphate — dehydrogenases consists in its participation in recovery of NADF providing regeneration of glutathione in erythrocytes (see Gloux the Tat it). The recovered glutathione protects erythrocytes from disintegration at contact with oxidizers (including medicinal substances). In a crust, time the St. 40 types of the pharmaceuticals provoking hemolysis at persons with insufficiency glyukozo-6-phosphate — dehydrogenases are known. Antimalarial means concern to them (see); streptocides, except for Ftalazolum, sulfaguanidine (see. Sulfanamide drugs); sulphones; nitrofurans (see); antituberculous remedies with tuberculostatic activity (see. Antituberculous remedies); antibiotics — streptomycin, levomycetinum, Amphotericinum In (see Antibiotics); analgesic means (see), and also antipyretics (see); G and K vitamins, Myarsenolum, nitroglycerine, Nevigramonum, Dimercaprolum, 5-NOK, L-DOFA, colchicine, methylene blue. These means at persons with insufficiency glyukozo-6-phosphate — dehydrogenases reduce the content of glutathione in erythrocytes, thereby promoting emergence of an acute intravascular hemolysis.

Hemolysis can arise also at persons with genetically caused insufficiency of glyukozo-6-fos-veils — dehydrogenases in erythrocytes at consumption of horse beans of Vicia faba or inhalations of their flower pollen (see the Favism). Hemolysis at such persons can be induced by endogenous intoxications, napr, diabetic acidosis (see a diabetes mellitus), a hepatargy (see), toxicosis of pregnant women (see); it can be provoked by introduction of a vaccine, and also intercurrent bacterial (colibacillus, proteas, a salmonella, a mycobacterium of tuberculosis), a rickettsial or viral infection. Acute hemolysis at a viral hepatitis is connected, apparently, as with immediate effect of a virus on a membrane of erythrocytes, and with the abnormal liver function leading to acidosis that at persons with insufficiency of enzyme can lead to a massive lysis of erythrocytes. Between degree of deficit of enzyme and hemolitic manifestations there is no strict correlation; this results from the fact that the data on reduced activity of enzyme received by in vitro do not reflect its kinetic properties, the shown in vivo at receipt in an organism of the hemolitic agent.

At insufficiency of a piruvatki-naza the crucial role in a pathogeny of hemolysis is played by disturbance of synthesis

of the ATP which is the main source of the energy necessary for erythrocytes for implementation of oxygen and transport function. Erythrocytes with insufficiency a feast-vatkinazy are exposed to sequestration and are englobed by splenic macrophages.

Pathological anatomy. At morfol. a research reveal the changes characteristic of hemolitic anemia (see), jaundices (see), increase in a spleen, liver, a hemosiderosis (see) bodies and fabrics.

The clinical picture is various: the asymptomatic forms and forms which are characterized by a wide range patol are observed. states (from the minimum hemolysis to heavy hemolitic crisis). The wedge, forms E allocate the following. and.: acute intravascular hemolysis; a favism (see); the acute hemolitic disease of newborns which is not connected with group and Rh incompatibility or with a hemoglobinopathy (see), complicated sometimes by a so-called kernicterus (damage of cherenno-brain nerves); hereditary chronic (not spherocytic) hemolitic anemia.

The acute intravascular hemolysis in hard cases proceeds with a picture of hemoglobinuric (chernovodny) fever, edges is clinically shown by a sudden fever, fervescence, a headache, vomiting. The main symptoms at the same time are the expressed haemoglobinaemia (see) which is not conjugated to a giperbilir a bi-nemiya (see), to hemoglobin a riya (see), the expressed anemia with giperretiku-lotsitozy, a normoblastemiya, Heinz's little bodies and basphilic stippling in erythrocytes (see Erythrocytes), a neutrophylic hyper leukocytosis (see the Leukocytosis), sometimes with a leukemoid test (see Leukemoid tests). In marrow the erythrophagocytosis is noted reactive eritro-blastoz. Feature of the hemolysis caused by pharmaceuticals is in its self-restriction, i.e. the sudden termination on 7 — the 12th day (even in case of continuation or resuming of reception of the same medicine) that glyukozo-6-phosphate — dehydrogenases of pharmaceuticals of population of erythrocytes, new, steady against action, with normal activity of enzyme has a talk receipt in a blood channel to replace the broken-up population of erythrocytes with insufficiency. At a favorable outcome there occurs recovery with normalization of a picture of blood. In some cases symptoms of the minimum hemolysis are constantly or periodically noted. In the most hard cases owing to obstruction of nephrons a blood detritis and deposits of hemosiderin in tubules of kidneys the anury develops (see) with uraemia (see) that leads to a lethal outcome.

The acute hemolitic disease of newborns caused by deficit glyukozo-6-phosphate — dehydrogenases, is most often provoked by reception of the pregnant woman or the nursing mother of pharmaceuticals with potentially hemolitic action; on a wedge, a picture it does not differ from the hemolitic disease of newborns connected with incompatibility of blood of mother and a fruit on a Rhesus factor or a blood group; it is characterized by yellowness of skin and mucous membranes, increase in a liver and spleen, changes in blood (see. Hemolitic disease of newborns).

Hereditary chronic (not - spherocytic) hemolitic anemia rather seldom occurs at carriers of nek-ry abnormal options glyukozo-6-phosphate — dehydrogenases. It is observed (on statistical data, approximately at 5 on 100 000 newborns) at insufficiency of a pyruvatekinase, a thicket at homozygotes (at autosomal a recessive nomas a mode of inheritance), is more rare at heterozygotes (at an autosomal domi-nantnom a mode of inheritance). The disease can be shown since the birth, from first months or the first years of life. At the same time pallor with an icteric shade of skin and mucous membranes, increase in a spleen is noted, is more rare than a liver. Anemia has normokhromny macrocytic character, the content in blood of reticulocytes is increased at the normal or increased osmotic resistance of erythrocytes; the raised not conjugated bilirubinemia is characteristic. Disease can escalate in connection with the hemolitic crises caused by reception of pharmaceuticals or an intercurrent infection. A frequent complication is calculous (owing to formation of pigmental stones) cholecystitis (see).

The diagnosis establish on the basis of the anamnesis (taking into account an ethnic origin of the patient), a wedge, pictures and results a lab. researches.

Treatment of acute hemolitic crisis is directed to stopping of hemolysis, prevention and elimination of shock (see) and anuries. For this purpose make intravenous infusions of Polyglucinum, dextran, polyvinylpirrolidone, and also sodium bicarbonate or sodium lactate. Cardiovascular means, osmotic di ~ uretik, Prednisolonum are shown; at a renal failure (azotemia) make a hemodialysis (see). At heavy hemolitic anemia transfusions washed and defrozen (after a cryopreservation) erythrocytes are necessary (see Hemotransfusion, Erie-trotsitnaya weight). At the minimum hemolysis appoint antioxidants — vitamin E (Erevitum), Riboflavinum. At an acute hemolitic disease of newborns make exchange hemotransfusion (see). At hereditary chronic (not spherocytic) hemolitic anemia with preferential sequestration of erythrocytes in a spleen the splenectomy is effective (see).

The forecast at acute hemolitic crisis is defined by massiveness of hemolysis, a functional condition of kidneys, timeliness and efficiency of treatment. In the cases complicated by an anury with development of a renal failure, the forecast adverse.

Prevention of acute hemolitic crisis consists in strict observance by persons with insufficiency glyukozo-6-phosphate — dehydrogenases of absolute failure from reception of potentially hemolitic means. Inoculations, and also donorship are contraindicated (in order to avoid disintegration of population of erythrocytes with insufficiency of enzyme in an organism of the recipient).

See also Hemolitic anemia.

Bibliography: Alekseev G. A. and Berliner G. B. Gemoglobinurii, page 15, M., 1972; Alekseev G. A., Ida - a dream L. I. and the Zhukovsky E. D. Acute medicinal hemolitic anemia at persons with inborn insufficiency in erythrocytes of a dehydrogenase of glyu-kozo-6-phosphate, Rubbed. arkh., t. 38, No. 8, page 52, 1966; Boytler E. Disturbances of metabolism of erythrocytes and hemolitic anemia, the lane with English, M., 1981; In about-ronov A. A., etc. Some patterns of distribution of deficit of G6FD enzyme to Transcaucasia, in book: Diseases of tropics and subtropics, under the editorship of

A. Ya. Lysenko, page 66, M., 1976; Krasnopolskaya K. D. and Shat-s Kaya T. L. Genetic heterogeneity of erythrocyte fermentopatiya, in book: Progress in medical genetics, under the editorship of

N. P. Bochkov, page 37, M., 1978; L e-

wines G. C., etc. Distribution of hemoglobinopathies and deficit of glyukozo-6-fosfatdegidrogenazy erythrocytes among residents of some areas of the Uzbek SSR, Probl. gematol. and modulation, blood, t. 19, No. 10, page 26, 1974; Hereditary anemias and hemoglobinopathies, under the editorship of Yu. N. Tokarev, etc., page 92, M., 1983; Standardization of methods of a research glyu-kozo-6-fosfatdegidrogenazy, the Report of science team of WHO, the lane with English, Geneva, 1968; Beutler E., Dem R. J. and. Alving A. S. Hemolytic effect of primaquine, study of primaquine — sensitive erythrocytes, J. Lab. clin. Med., v. 44, p. 177, 1954; Z a n e 1 1 an A. o. Membrane abnormalities of pyruvate kinase deficient red cells, Brit. J. Haemat., v. 42, p. 101, 1979. G. A. Alekseev.