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See ((Thalassemia))
Alpha-thalassemia-α-thalassemia.
A form of thalassemia involving the genes HBA1 and HBA2.
Alpha-thalassemias are most commonly inherited in a Mendelian recessive manner.
Associated with deletions of chromosome 16p.
Rarely can also be acquired.
Alpha-thalassemia is due to impaired production of alpha chains from 1, 2, 3, or all 4 of the alpha globin genes, leading to a relative excess of beta globin chains.
The clinical phenotype that is present depends on how many genes are affected.
The presentation of individuals with alpha-thalassemia consists of;
Jaundice
Fatigue
Pronounced forehead
Gallstones
Hypertension during pregnancy
Resulting in an excess of β chains in adults and excess γ chains in newborns.
Excess β chains form unstable tetramers called hemoglobin H or HbH of four beta chains.
The excess γ chains form tetramers which are poor carriers of O2 since their affinity for O2 is too high, so it is not dissociated in the periphery.
Homozygote α0 thalassaemias, where numerous γ4 but no α-globins occur at all, referred to as Hb Barts, often result in death soon after birth.
Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and molecular diagnosis.
Alpha-thalassemia can be mistaken for iron-deficiency anemia on a full blood count or blood film, as both conditions have a microcytic anemia.
Serum iron and serum ferritin can be used to exclude iron-deficiency anemia.
Two genetic loci exist for α globin, thus four alleles are in diploid cells: Two alleles are maternal and two alleles are paternal in origin.
The severity of the α-thalassemias is correlated with the number of affected α-globin; alleles: the greater, the more severe will be the manifestations of the disease.
With one α-globin allele affected, known as alpha thalassemia silent, the effect on hemoglobin synthesis is minimal, as three α-globin genes are enough to permit normal hemoglobin production.
With alpha thalassemia silent no clinical symptoms present.
With alpha thalassemia trait; two α genes permit nearly normal production of red blood cells, but a mild microcytic hypochromic anemia is seen.
Alpha thalassemia trait can be mistaken for iron-deficiency anemia and treated inappropriately with iron.
Alpha-thalassemia trait can exist in two forms: Alpha-thal-1 (- -/α α) and Alpha-thal-2 (- α/- α).
Alpha-thal-1 (- -/α α), involves cis deletion of both alpha genes on the same chromosome.
Alpha-thal-1 (- -/α α) incidence is higher in people of Asian descent when compared with the general population.
Alpha-thal-2 (- α/- α), involves trans deletion of alpha genes; this occurs on different chromosomes.
Alpha-thal-2 (- α/- α) has a higher incidence in people of African descent when compared with the general population.
Hemoglobin H disease; two unstable hemoglobins are present in the blood; hemoglobin Barts (tetrameric γ chains) and hemoglobin H (tetrameric β chains).
Both of these unstable hemoglobins have a higher affinity for oxygen than normal hemoglobin.
A microcytic hypochromic anemia with target cells and Heinz bodies which is precipitated HbH on the peripheral blood smear can occur, as well as hepatosplenomegaly.
The disease is noticed in childhood or in early adult life; anemia and hepatosplenomegaly are noted.
Alpha thalassemia major; these fetuses are edematous, have little circulating hemoglobin, and the hemoglobin that is present is all tetrameric γ chains.
When all four alleles are affected, the fetus will not survive gestation without in utero intervention.
Most infants with alpha-thalassemia major are stillborn with hydrops fetalis.
Fetuses treated with intrauterine transfusions throughout pregnancy can survive to birth with acceptable morbidity.
After birth, the treatment options include bone marrow transplantation or continued chronic transfusions.
Treatment for alpha-thalassemia may consist of blood transfusions, possible splenectomy, and gallstones may be a problem.
Stem cell transplantation should be considered as a treatment.
Worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role.