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Alpha-thalassemia
Classification and external resources
ICD-10 D56.0
ICD-9 282.4
OMIM 141800
DiseasesDB 448 33334, 33678
MeSH D017085
GeneReviews Alpha-Thalassemia

Alpha-thalassemia (α-thalassemia) is a form of thalassemia involving the genes HBA1 [1] and HBA2 [2].

Contents

Causes

It is most commonly inherited in a Mendelian recessive fashion. It is also connected to the deletion of the 16p chromosome.

It can also be acquired.[3]

Pathophysiology

α thalassemias result 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 4 beta chains) which have abnormal oxygen dissociation curves. 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 there is lots of γ4 but no α-globins at all (referred to as Hb Barts), often result in still birth.

Types

There are two genetic loci for α globin, and thus four alleles. Two alleles are maternal in origin and two alleles are paternal in origin. The severity of the α thalassemias is correlated with the number of affected α globin allele: the greater the number of affected loci, the more severe will be the manifestations of the disease.

When noting the genotype, a "-" indicates an absence of function, and a "α" indications a functional alpha chain. (In contrast to the "βo" and "β+" notation used in beta-thalassemia, in alpha-thalassemia a distinction between absent and reduced function is not usually noted.)

Alleles affected Description Genotype
One There is minimal effect. Three α-globin alleles are enough to permit normal hemoglobin production, and there are no clinical symptoms. They have been called silent carriers. They may have a slightly reduced mean corpuscular volume and mean corpuscular hemoglobin. -/α α/α
Two The condition is called alpha thalassemia trait. Two α alleles permit nearly normal erythropoiesis, but there is a mild microcytic hypochromic anemia. 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:

  • one form, associated with Asians, involves cis deletion of both alpha alleles on the same chromosome;
  • the other, associated with black people, involves trans deletion of alpha alleles on different (homologous) chromosomes.
-/- α/α or
-/α -/α
Three The 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, resulting in poor oxygen delivery to tissues. There is a microcytic hypochromic anemia with target cells and Heinz bodies (precipitated HbH) on the peripheral blood smear, as well as splenomegaly. The disease may first be noticed in childhood or in early adult life, when the anemia and splenomegaly are noted. -/- -/α
Four The fetus cannot live once outside the uterus and may not survive gestation: 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). -/- -/-

References

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