Hereditary abnormalities of the A. fraction of human hemoglobin may be: (a) structural, in which a genetically determined change in the amino acid composition and sequence of either the alpha or the delta polypetide chains, results in the production of a hemoglobin A variant and (b) quantitative, in which changes in concentration in the hemoglobin A₂ fraction occur as a result of activation or repression of the genes for either the alpha or the delta chains or as a result of the replacement of the normal genes for either of these chains by structurally mutant genes. Because the beta and delta chains of human hemoglobins are linked, a number of conditions also involving the beta chain genes (delta-beta hybrid chain hemoglobins, hereditary persistence of fetal hemoglobin, the beta thalassemias) produce changes in hemoglobin A₂ concentration. Several non-hereditary states have been shown to produce quantitative changes in the hemoglobin A₂ fraction.

peer-reviewed