details about alpha thelessemia and beta thelessemia?!
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details about alpha thelessemia and beta thelessemia
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Alpha (α) thalassemias
The alpha thalassemias involve the genes HBA1 (OMIM 141800) and HBA2 (OMIM 141850), inherited in an autosomal co-dominant fashion. α thalassemias result in excess β chain production in adults and excess γ chains in newborns. The excess β chains form unstable tetramers that have abnormal oxygen dissociation curves.
There are four genetic loci for α globin. The more of these loci that are deleted or affected by mutation, the more severe will be the manifestations of the disease:
If all four loci are affected, the fetus cannot live once outside the uterus: most such infants are dead at birth with hydrops fetalis, and those who are born alive die shortly after birth. They are edematous and have little circulating hemoglobin, and the hemoglobin that is present is all tetrameric γ chains (hemoglobin Barts). Usually, this involves homozygous inheritance of an alpha thalassemia trait, type 1.
If three loci are affected, Hemoglobin H disease results. Two unstable hemoglobins are present in the blood, both hemoglobin Barts (tetrameric γ chains) and hemoglobin H (tetrameric β chains). There is a microcytic hypochromic anemia with target cells and Heinz bodies (precipitated Hb H) on the peripheral blood smear. The disease may first be noticed in childhood or in early adult life, when the anemia and splenomegaly are noted. This is usually due to compound heterozygous inheritance of alpha thalassemia type 1 and type 2 traits.
If two of the four α loci are affected, alpha thalassemia trait, type 1 results. Two α loci permit nearly normal erythropoiesis, though there is a mild microcytic hypochromic anemia. There is a high prevalence (about 30%) of deletion of one of the two α loci on chromosomes of people of recent African origin, and so the inheritance of two such chromosomes is not uncommon. The disease in this form can be mistaken for iron deficiency anemia and treated inappropriately with iron. Two modes of alpha thalassemia trait, type 1 has been noted. One involves cis deletion of two alpha loci on the same chromosome; another involves trans deletion of allelelic genes on homologous chromosomes (no. 16).
If one of the four α loci is affected, alpha minor or alpha+ thalassemia trait or alpha thalassemia trait, type 2 results and there is minimal effect. Three α-globin loci are enough to permit normal hemoglobin production, and there is no anemia or hypochromia in these people. They have been called α thalassemia carriers.
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Beta (β) thalassemias
Beta thalassemia is due to mutations in the HBB gene on chromosome 11 (OMIM 141900), also inherited in an autosomal co-dominant fashion. In β thalassemia, excess α chains are produced, but these do not form tetramers: rather, they bind to the red blood cell membranes producing membrane damage, and at high concentrations have the tendency to form toxic aggregates. The severity of the damage depends on the nature of the mutation. Some mutations (βo) prevent any formation of β chains; others (β+) allow some β chain formation to occur. Recently, increasing reports suggest that upto 5% of patients with beta-thalassemias produce fetal hemoglobin (HbF), and use of hydroxyurea also has a tendency to increase the production of HbF, by as yet unexplained mechanisms.
Any given individual has two β globin alleles:
If both have thalassemia mutations, a severe microcytic, hypochromic anemia called β thalassemia major or Cooley's anemia results. Untreated, this results in death before age twenty: treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of transfusion-caused iron overload. Cure is possible by bone marrow transplantation.
If only one β globin allele bears a mutation, β thalassemia minor results (sometimes referred to as β thalassemia trait). This is a mild anemia with microcytosis. Symptoms include weakness and fatigue - in most cases β thalassemia minor may be asymptomatic and many people may be unaware they have this disorder. Detection usually involves counting the mean corpuscular volume (size of red blood cells) and noticing a slightly decreased mean volume than normal.
Thalassemia intermedia is a condition intermediate between the major and minor forms. Sufferers can often manage a normal life but may need occasional transfusions e.g. at times of illness or pregnancy. This really depends on the severity of their anemia.
The actual genetic cause of β thalassemias are actually very diverse and a number of different mutations can cause reduced or absent β globin synthesis. Usually, superscripts 0 and + are added to β to indicate complete absence, and deficient synthesis of β globins respectively.
Mainly there are two forms of genetic defects which produce β thalaseemias:
Nondeletion forms: These defects generally involve a single base substitution or small deletion or inserts near or upstream of the β globin gene. Most commonly, mutations occur in the promotor regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease.
Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (βo) or hereditary presistance of fetal hemoglobin syndromes.
Other Answers:
first and second degree.
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merlin
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