Thalassemias represent heterogeneous group of a hemoglobinopathy which cornerstone decrease in synthesis of the polypeptide chains entering into structure of normal hemoglobin A is.
Epidemiology The beta talassemia occurs among the people of all continents with various frequency. Data and on prevalence and - thalassemias collect. Considerable frequency of heterozygous options of a disease is observed mainly on the coast of the Mediterranean Sea, in Southern Europe, North Africa, Southern and Southeast Asia. There are local centers of a thalassemia in Azerbaijan in which low regions the heterozygous beta talassemia is observed at 7 — 10% of the population.
Etiology and pathogeny In a pathogeny of clinical manifestations of a thalassemia major importance has disturbance of synthesis of chains of a globin. Unlike the homozygous beta talassemia which is result of inheritance by the child from both parents of a gene of this pathology, the heterozygous beta talassemia (A2) develops at inheritance only of one mutant allele causing reduction in the rate of synthesis of beta chains. The heterozygous deltabeta-thalassemia (G) represents result of a mutation of the gene causing simultaneous oppression of speed of synthesis delta and beta chains. In a basis and - thalassemias disturbance of synthesis and - chains lies. As this chain is a part of all normal fractions of hemoglobin, at this disease their uniform decrease is observed.
Classification Thalassemias meet in gomo-and heterozygous forms, clinically share on big, intermediate, small and minimum. On degree of manifestation of clinical manifestations distinguish: the severe form which is coming to an end with death of the patient in the period of a neonatality chronic moderately severe when patients live up to school age and chronic with an easy current at which patients live up to mature age.
Approximate formulation of the diagnosis: Homozygous beta talassemia with heavy hemolitic anemia, gepato-and a splenomegaly, tower type of a skull and a mongoloidnost of the person, bilirubinovy stones in bilious ways, yellowness of skin, shin ulcers; in blood targetoid erythrocytes, erythro-normoblasts, irritation of an erythro-normoblastic sprout in marrow.
Clinic The homozygous beta talassemia (a big thalassemia, anemia Sacks) is characterized by sharp decrease in formation of HbA1, significant increase in maintenance of HbF, the low, normal or increased maintenance of HbA2. The maintenance of NBF can fluctuate from 30 to 90%, sometimes there are lower than 10%.
The course of a disease is characterized by the heavy hemolitic anemia which is shown by the end of the first year of life of the child, gepato-and a splenomegaly, a mongoloidiost of the face and a tower skull, lag of the child in physical development frequent yellowness and pallor of integuments. At part of patients ulcers in shins develop.
Radiological find a symptom of "hedgehog" or "brush" which is positive at increase in maintenance of HbF, it is negative at increase in percent of HbA2. At children aged from 6 months till 1 year in ossicles of feet and brushes thinning of a bast layer with swelling of a bone and formation of grubosetchaty structure of marrow comes to light. Since 1st year of life of the child the disturbance of development of bones which is quickly progressing till the puberty period is noted.
It is long the continuing hemolysis (a reticulocytosis, increase in free fraction of bilirubin of blood serum, an urobilinuria, a hyper sideremia), frequent transfusions of eritrotsitny weight lead to development of a hemosiderosis of a liver and spleen. Quite often there is a formation of bilirubinovy stones in bilious ways.
Level of hemoglobin reaches 30 — 50 g/l, a color indicator 0> 5 and below. In blood smears find the targetoid erythrocytes differing in a small hemoglobin content and shortening of life expectancy, anizopoykilotsitoz, eritro-and normoblasts. Increase of osmotic firmness of erythrocytes, a leukopenia is noted (in the period of hemolitic crisis). In marrow — irritation of an erythro-normoblastic sprout. Sometimes there are aplastic crisis or the phenomena of a hypersplenism.
At a heavy homozygous thalassemia patients die on the first year of life, at rather quieter form of a disease they can live up to adult age.
The heterozygous beta talassemia proceeds in a type of both asymptomatic, and manifest forms with slightly increased spleen, specific bone changes quite often expressed by hypochromia anemia frequent an anisocytosis, a poikilocytosis and the mishenevidnost of erythrocytes raised by their osmotic resistance increase in quantity of HbA2 (approximately to 8% of the general hemoglobin), at part of patients — HbF (to 5%).
At a heterozygous delta beta talassemia (F) the high content of HbF at the normal HbA2 level is noted. Clinical signs and hematologic shifts are similar meeting at a heterozygous beta talassemia.
Homozygous forms of a delta beta talassemia (F) are shown by almost same kliniko-hematologic disturbances, as a homozygous beta talassemia. Only HbF is found in patients with this form of a disease.
It is possible to distinguish persons from patients with a thalassemia with hetero-and the homozygous A2F-thalassemias forms which on the signs characterizing their current in essence differ from a beta talassemia a little.
In group of patients with a beta talassemia cases of a big thalassemia meet the expressed clinical manifestations less than intermediate and small forms. At inspection of relatives of patients the minimum form of a beta talassemia is found more often.
Allocate the following forms and - thalassemias: a fruit edema with Bart's hemoglobin (u4). a hemoglobinopathy of N (beta4), and - a thalassemia-1 and and - a thalassemia-2.
Edema of a fruit represents a homozygous state (on genes and - th-l), incompatible with life. Pregnancy in similar cases involuntarily is interrupted and at a fruit reveal a brain edema, a hepatomegalia. Electrophoretic research of hemoglobin Hb Bart's is found (80 — 90%, NBN which is combined with traces.
The hemoglobinopathy of N — one of options and - thalassemias — is shown by hemolitic anemia, increase in a spleen, the heavy course of bone changes. The picture of peripheral blood is characterized by lowering of a hemoglobin content, anizo-and a poikilocytosis, a hypochromia and multiple inclusions in erythrocytes (the hemoglobin N which dropped out in a deposit). Heterozygous forms and - thalassemias come to light at N.' a-Talassemiya-1 (a small form of a disease) sick with a hemoglobinopathy relatives arises at a combination of a gene and - th-l with a normal gene of a-tsepochkovogo of synthesis. It is characterized by small anemia, moderated anizo-and a poikilocytosis, intra erythrocyte inclusions, the increased osmotic resistance of erythrocytes. At adult patients and - a thalassemia-1 gemoglobinovy fractions happen within norm, at newborns Hb Bart's (5 — 10%) comes to light. a-Talassemiya-2 (the minimum form of a disease) develops at a-th-2 gene combination to a normal gene and-tsepochkovogo synthesis. Clinical manifestations are absent.
Verification of the diagnosis It is easy to confirm existence of a homozygous beta talassemia with research of content of fetalis hemoglobin in erythrocytes (it is increased to 20 — 90%) and A2 hemoglobin. However at a beta talassemia combination to a delta thalassemia synthesis not only beta, but also the delta chain which is a part of A2 hemoglobin in this connection its contents can be normal or, on the contrary, even sharply lowered is broken.
The diagnosis of a heterozygous beta talassemia is confirmed on the basis of increase of maintenance of fraction of A2 hemoglobin. for this purpose use an electrophoresis on an atsetattsellyuloza. Approximately at a half of patients quantitative increase in fetalis hemoglobin comes to light (to 2,5 — 7%). A diagnostic character is also existence of a similar disease at members of the family of the patient.
At and - thalassemias unlike a beta talassemia the content of fetalis hemoglobin and A2 hemoglobin does not increase. and - the thalassemia can be diagnosed by means of studying of biosynthesis of chains of a globin of in vitro, the Bart's hemoglobin deprived and - chains is found in newborns sometimes at a blood analysis by an electrophoretic method. For diagnosis of heterozygous forms and - thalassemias use determination of specific activity and - and globin beta chains.
Treatment In treatment beta and and - thalassemias generally apply transfusions of the washed or defrozen erythrocytes, desferal, according to indications — a splenectomy.