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Alpha( ) thalassemia is subclassified into the following three general forms on the basis of the number of inherited alpha genes.Persons who inherit 3 normal alpha-globin genes (-α/αα) are referred to clinically as silent carriers.Healthy individuals have 4 alpha-globin genes, 2 on each chromosome 16 (αα/αα; see the image below).Alpha thalassemia syndromes are caused by deficient expression of 1 or more of the 4 alpha-globin genes on chromosome 16 and are characterized by absent or reduced synthesis of alpha-globin chains.The oxygen carrying capability of the red blood cells (RBCs) relies on hemoglobin, a tetramer protein that comprises 4 globin chains bound to the heme molecule.There are 4 major types of globins: alpha (α), beta (β), gamma (γ), and delta (δ).Some subclasses are present within the latter category, based on the number of genes affected.In all, there are four general forms of alpha thalassemia.

The resulting disorder is referred to as hydrops fetalis, alpha thalassemia major, or hemoglobin Bart’s.Individuals with thalassemia syndrome are most often of African, Asian, Mediterranean, or Middle Eastern descent.Mutations and gene deletions causing the various thalassemia genotypes have arisen independently in different populations but have subsequently propagated by means of natural selection.Individuals with this disorder cannot produce any functional alpha globin and thus are unable to make any functional hemoglobin A, F, or A2.

Hydrops fetalis is incompatible with extrauterine life.

Inheritance of 2 normal alpha-globin genes through either heterozygosity for alpha(0) thalassemia (αα/--) or homozygosity for alpha( ) thalassemia (-α/-α) results in the development of alpha thalassemia trait, also referred to as alpha thalassemia minor or alpha thalassemia-1 trait.