Analyse moléculaire et diagnostic prénatal de la b-thalassémie: à propos de notre expérience en Tunisie centrale Volume 58, numéro 4, Juillet – Août Le terme thalassémie est un terme générique pour désigner un tableau clinique résultant d’une diminution quantitative de la synthèse d’une chaîne de globine. selenium, and copper in 64 children with B-thalassaemia major and 63 age- and zinc, sólénium et cuivre sériques chez 64 enfants atteints de B-thalassemie.
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They are forms of thalassemia caused by reduced or absent synthesis thaassemie the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one inThe severity of the disease depends on the nature of the mutation. HBB blockage over time leads to decreased beta-chain synthesis.
Thalassemia – Wikipedia
The body’s inability to construct new beta-chains leads to the underproduction of HbA. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Repeated blood transfusions can lead to build-up of iron overloadultimately resulting in iron toxicity.
Three main forms have been described: All people with thalassemia are susceptible to health complications that involve the spleen which is often enlarged and frequently removed and gallstones.
Individuals with beta thalassemia major usually present within the first two years of life with severe anemia, poor growth, and skeletal abnormalities during infancy. Untreated thalassemia major eventually leads to death, usually by heart failure ; therefore, birth screening is very important.
Excess iron causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosisliver fibrosisand in extreme cases, liver cancer. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia and increased red blood cell destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.
Beta thalassemia is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases,  an inherited mutation damages the assembly of the messenger-type RNA mRNA that is transcribed from a chromosome. DNA contains both the instructions genes for stringing amino acids together into proteinsas well as stretches of DNA that play important roles in regulating produced protein levels.
In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions are included in the mRNA. This happens because the mutation obliterates the boundary between the intronic and exonic portions.
Hemoblogin’s normal alpha and beta subunits each have an iron-containing central portion heme that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits. Since the mutation may be a change in only a single base single-nucleotide polymorphismon-going efforts seek gene therapies to make that single correction.
Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on your family history, if your parents or grandparents suffered from beta thalassemia there is a high probability of the mutated gene being inherited by an offspring.
Even if a child does not have beta thalassemia major, they can still be a carrier resulting in future offspring having beta thalassemia. Another risk factor is because of certain ancestry.
Abdominal pain due to hypersplenism and splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. Physicians note these signs as associative due to this disease’s complexity.
Based on symptoms, tests are ordered for a differential diagnosis. These tests include complete blood count ; hemoglobin electrophoresis ; serum transferrinferritintotal iron-binding capacity ; urine urobilin and urobilogen; peripheral blood smearwhich may show codocytesor target cells;  hematocrit ; and serum bilirubin.
All beta thalassemias may exhibit abnormal red blood cells, a family history is followed by DNA analysis. Family studies can be done to evaluate carrier status and the types of mutations present in other family members.
DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin.
A study aimed at detecting the genes that could give rise to offspring with sickle cell disease. Of 10, patients, 1, patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples.
The decrease in incidence has benefitted those affected with thalassemia, as the demand for blood has decreased, therefore improving the supply of treatment. Affected children require regular lifelong blood transfusion and can have complications, which may involve the spleen.
Bone marrow transplants can be curative for some children. Advances in iron chelation treatments allow patients with thalassemia major to live long lives with access to proper treatment.
Popular chelators include deferoxamine and deferiprone. The most common patient deferoxamine complaint is that they are painful and inconvenient. The oral chelator deferasirox was approved for use tgalassemie in some countries,   it offers some hope with compliance at a higher cost. Bone marrow transplantation is the only cure and is indicated for patients with severe thalassemia major.
Transplantation can eliminate a patient’s dependence on transfusions. Absent a matching donor, a savior sibling can be conceived by preimplantation genetic diagnosis PGD to be free of the disease as well as to match the recipient’s human leukocyte antigen HLA type. Scientists at Weill Cornell Medical College have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. Patients with thalassemia major are more inclined to have a splenectomy.
The medical cases of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Patients with hypersplenism are inclined to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. Iron rich patients need a splenectomy to reduce the probability of an iron overload. The different surgical techniques are the open and laparoscopic method. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism.
Surgeons who chose Laparoscopic splenectomy must administer an appropriate immunization at least two weeks before the surgery. The camera is inserted along with four other trocars: Patients are transfused by meeting strict criteria ensuring their safety. To ensure quality blood transfusions, the packed red blood cells should be leucoreduced with a minimum of 40g of hemoglobin content.
By having leucoreduced blood packets, the patient is at a thalxssemie risk to develop adverse reactions by contaminated white cells and preventing platelet thslassemie. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens.
Iron overload is an unavoidable consequence of chronic transfusion therapy, necessary for patients with beta thalassemia. Iron chelation is a medical therapy that avoids the complications of iron overload. The iron overload can be removed by Deferasirox, an oral iron chelator, which has a dose- dependent effect on iron burden. Deferasirox is a vital part in the patients health after blood transfusions. It represents a potentially toxic iron form due to its high propensity to induce oxygen species and is responsible for cellular damage.
The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. Patients may require episodic blood transfusions. Transfusion-dependent patients develop iron overload and require chelation therapy  to remove the excess iron. Transmission is autosomal recessive ; however, dominant mutations and compound heterozygotes have been reported.
Genetic counseling is recommended and prenatal diagnosis may be offered. Patients are often monitored without treatment. While many of those with minor status do not require transfusion therapy, they still risk iron overload, particularly in the liver.
A serum ferritin test thalqssemie iron levels and can point to further treatment. Minor often coexists with other conditions such as asthma and can cause iron overload of the liver and in those with non-alcoholic fatty liver diseaselead to more severe outcomes.
The beta form of thalassemia is particularly prevalent among the Mediterranean peoples and this geographical association is responsible for its naming: In Europethe highest concentrations of the disease are found in Greece and the Turkish coastal regions.
The major Mediterranean islands except the Balearics such as SicilySardiniaCorsicaCyprusMalta and Crete are heavily affected in particular. The thalassemia trait may confer a degree of protection against malaria which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers known as heterozygous advantagethus perpetuating the mutation.
In that respect, the various tgalassemie resemble another genetic disorder affecting hemoglobin, sickle-cell disease.
The disorder affects all genders but is more prevalent in certain ethnicities and age groups. There have been 4, hospitalized cases in England in and 9, consultant episodes for thalassemia. It is usually fatal in infancy if blood transfusions are not initiated immediately. From Wikipedia, the free encyclopedia.
Beta thalassemia Beta thalassemia genetics, the picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome A child inherits two beta globin genes one from each parent.
Retrieved 4 April Orphanet J Rare Dis. Orphanet Journal of Rare Diseases. Expert Consult – Online. Oxford Handbook of Clinical Pathology.
Textbook of Inpatient Management. Iron Physiology and Pathophysiology in Humans. Handbook of Iron Overload Disorders.