|Alpha-thalassemia inheritance pattern|
|Causes||Deletions of chromosome 16p.|
|Diagnostic method||Haemoglobin electrophoresis|
|Treatment||Blood transfusion, possible splenectomy|
Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. 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 degree of impairment is based on which clinical phenotype is present (how many genes are affected).
Alpha-thalassemias are most commonly inherited in a Mendelian recessive manner. They are also associated with deletions of chromosome 16p. Alpha thalassemia can also be acquired under rare circumstances.
The mechanism sees that α thalassemias results in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The 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 anaemia on a full blood count or blood film, as both conditions have a microcytic anaemia. Serum iron and serum ferritin can be used to exclude iron-deficiency anaemia.
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. When noting the genotype, an "α" indicates a functional alpha chain, and '-' a pathological one.
|One||This is known as alpha thalassemia silent and with this type, the effect on hemoglobin synthesis is minimal. Three α-globin genes are enough to permit normal hemoglobin production, and no clinical symptoms present. It occurs due to a deletion or non-deletion mutation.||- α/α α|
The condition is called alpha thalassemia trait; two α genes permit nearly normal production of red blood cells, but a mild microcytic hypochromic anemia is seen. The disease in this form can be mistaken for iron-deficiency anemia and treated inappropriately with iron.
Alpha-thalassemia trait can exist in two forms:
|- -/α α|
- α/- α
|Three||This condition is called 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 (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.[medical citation needed]||- -/- α|
|Four||This is known as 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 likely 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 starting at an early gestational age can survive to birth with acceptable morbidity. After birth, the treatment options include bone marrow transplantation or continued chronic transfusions.||- -/- -|
|α α/α α = normal: 'α α' before the '/' represents one chromosome, and 'α α' after the '/', its homologous chromosome.|
Treatment for alpha-thalassemia may consist of blood transfusions, and possible splenectomy; additionally, gallstones may be a problem that would require surgery. Secondary complications from febrile episode should be monitored, and most individuals live without any need for treatment
A study by Kreger et al combining a retrospective review of three cases of alpha thalassemia major and a literature review of 17 cases found that in utero transfusion can lead to favorable outcomes. Successful hematopoietic cell transplantation was eventually carried out in four patients.
In terms of epidemiology, worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role. Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean Basin, and generally tropical (and subtropical) regions. The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. More specifically, HbH disease is seen in Southeast Asia and the Middle East, while Hb Bart hydrops fetalis is acknowledged in Southeast Asia only. The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes.
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