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Thalassaemia
The thalassaemias are forms of anemia associated with hereditary haemoglobinopathies (deficiency in the synthesis of one or more of the four channels forming the hemoglobin in red blood cells). This translates into a sizable anemia. There is also an enlargement of the spleen and deformities of the skull and long bones in this disease.
Etiology
Alpha-thalassemia
The alpha-thalassemia are characterized by a deficit of chain alpha-globin in hemoglobin. They therefore affect the synthesis of hemoglobin 3 kinds: HbA, HbA2 and HbF, since all contain the alpha chain, in which case life is possible only through the formation of large quantities of abnormal hémoglobines did component chains whose synthesis is not hindered: HbH and Hb Bart's. These diseases are rare and localized racial distribution.
Beta-thalassemia
The β-thalassemia are characterized by the absence of the β chain of hemoglobin. Only the synthesis of HbA is hampered.
We n'étudierons the most common variety, which is thalassemia classical or Mediterranean anemia Cooley
Description
Alpha-thalassemia
The alpha-thalassemia are common in endemic areas for malaria because they offer partial protection against the disease. They reflect a deficit chain alpha-globin in Hb = hemoglobin. This defect is expressed as soon as fetal life sub-unit is the alpha fetal hemoglobin (alpha 2 gamma2). Each chromosome genes Gate 2 alpha (= 4 alleles in total); classification of alpha-thalassemia is therefore more complex than for beta-thalassemia. If no allele-alpha is functional, the fetus died in utero. If 2 or 3 alleles are functional, the patient will suffer a microcytic anemia and hypochromic (alpha1 or alpha2-thalassemia). If only one allele is functional, this genotype will give the patient a hémoglobinose H. This alpha-thalassemia a symptom for chronic hemolytic anemia without néccessiter for all transfusions. Missing alpha-globin, tétramères-gamma (fetal life) or beta (after birth) induirent will accumulate and damage the red blood cells which transport them, they will die in traffic after about 45 days. These red blood cells abimés will be recovered by the macrophages. The processing is done by supplementation with vitamin B9 or folic acid and vitamin B12 and care rapid infections (and any other precipitating factors).
Beta-thalassemia
The genes of hemoglobin are worn by chromosomes 11 (chains type b, g and d) and 16 (a type chains). In érythroblaste normal, there is a perfect balance of synthesis of chains globin between these chromosomes 2. In the fetus, fetal hemoglobin (HbF), composed of channels 2 and alpha 2 chains gamma (2a2g) is in the majority. At birth, the rate is 85%. This rate gradually decreases to less than 1% at age 6 to 12 months. The molecular formula adult has 97 to 98% hemoglobin A (a2b2) and 2 to 3% hemoglobin A2 (a2d2). The thalassaemias are the result of mutations in genes leading to a judgement (a0 or b0-thalassemia) or a reduction of synthesis (a + b + or - thalassemia) a chain globin. In the beta-thalassemia heterozygous, there is a decrease of synthesis of hemoglobin rise to the microcytosis and hypochromia. The small size of red blood cells is offset by their number from which a pseudo-polycythemia (6 to 7 million cell / mm ³). In addition, the relative increase synthesis chains led to the rise in hemoglobin A2 (> 3.5%).
In homozygous beta-thalassemia, excess relative channels in rushing and leads the érythroblaste lysis by its toxicity membrane that is causing an ineffective erythropoiesis. The érythroblastes able to synthesize hemoglobin F manage to produce and GR reticulocytes (red blood cells) mature. The GR are circulating microcytaires ie small, distorted (poïkilocytose) and have a shorter lifespan.
Anaemia in thalassemia major ie homozygous is due to 2 mechanisms: erythropoiesis inefficient and hyperhémolyse. The anemia induced a deep hypersecretion Erythropoietin induces stimulation of erythropoiesis. The expansion of this sector can reach 30 times normal. This has the consequence of bone deformities affecting the skull bones, the region Malar, jaw and the ends of long bones mainly. In addition, hyperhémolyse and myeloid metaplasia are at the root of the enlarged spleen and liver enlargement. Finally these patients often overload martial in connection with the digestive hyperabsorption iron and especially transfusions iterative; martial overload which can lead to hemochromatosis with its complications endocrine, cardiac and liver.
Incidence and prevalence
Frequently in endemic areas for malaria because they help protect carriers against malaria (often lethal in developing countries).
Diagnosis
* Anemia <7> 5 to 7 million / mm ³, a hypochromia and HbA2> to 3.5%.
Treatment
Transfusion of red blood cells depending on the dosage of hemoglobin, about once a month.
The treatment transfusion now a hemoglobin level around 12 g / l avoids the appearance of clinical signs. It is kept alive if allogeneic marrow is impossible.
Genetic
The genotypic diagnosis of molecular lesions officials, prepared by molecular biology, is not necessary for the diagnosis, but necessary prenatal diagnosis.
Sources
* (A) Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 604131
* (A) GeneTests: Medical Genetics Information Resource (online database). Copyright, University of Washington, Seattle. 1993-2005
* (En) thalassemie medsante.
Thalassaemia classical or Mediterranean anemia Cooley
Geographic distribution
The gene thalassémique is widespread in white populations occupying the edges of the Mediterranean (Thalassa = Wednesday in Ancient Greek), Corsica and Italy and especially in the Po delta, Sardinia, Sicily; Greece, Crete, Cyprus, Syria and Turkey.
Other homes (perhaps due to a different allele) exist in Thailand, India, China, the Philippines and in some places in Africa.
It is suspected malaria also have played a role in these distributions. (The malaria has been eradicated in Italy under Mussolini only recently.)
Pathogénie
* The situation is completely normal before birth because the synthesis of HbF is not affected. Normally, shortly before birth, the synthesis of chains Beta and Delta begins to move, while those channels Gamma stops almost completely. At this moment begins the gradual replacement of HbF in GR by the HbA and the Hba2. At the time of birth, HbA already represents 10 to 40% of the total blood haemoglobin.
* At the thalassémique homozygous, the synthesis of HbA does not start and the HbF continues throughout life post. The G.R. are thus deprived of HbA and contain the place of HbF. However, the rate of synthesis of HbF after birth is not enough by far to cover the needs of hematopoiesis, so that it occurs extremely hypochromic anemia. This anaemia is also hemolytic because GR poor are structurally abnormal Hb (microplatycytose) and have an average life very shortened. The table thus formed is known as thalassemia major.
* At the thalassémique heterozygous (bearer of "dealing"), the synthesis of HbA takes place, albeit at a speed slightly inadequate. The disease is therefore qualified thalassaemia minor.
Laboratory tests
The review shows haematological extremely hypochromic anemia and microcytic is in this condition that the discrepancy between the number of GR (usually 2 to 3 x 10 exhibitor 6/mm ³) on the one hand and the rate of Hb and hematocrit on the other hand is most pronounced. In smear blood among the oddities of form that can be observed, the most characteristic is the hématie a target (target cell), where the hemoglobin of the blood is gathered in a ring at the periphery and in a central bulge. The resistance of osmotic G.R. is increased, because their thinness allows them swelling important before the break. The analysis methods combined electrophoresis and denaturalization alkaline shows that HbA is absent, the lack of HbA2 usual too, while HbF is only present in the globular hemolysate.
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