Hb E and alpha-thalassemia; variability in the assembly of beta E chain containing tetramers

The level of Hb E (including Hb A2) was quantitated in 30 adult Hb E heterozygotes by cation exchange high performance liquid chromatography; in 20 subjects the alpha-globin gene status was determined by gene mapping and polymerase chain reaction methodology. A decrease in Hb E level was observed which was directly related to the type of alpha-thalassemia that was present; the lowest percentage of Hb E (and Hb A2) was 10.2%, seen in two persons with Hb Constant Spring (CS)-Hb H disease (alpha CS alpha/--). Similar analyses were made for several newborn babies with a Hb E heterozygosity, the Hb E level was determined as beta E by a reversed phase high performance liquid chromatographic procedure. One baby with Hb E trait and Hb H disease (-alpha/--) had a beta E level of 17.7% (as % of beta A + beta E) comparable to that seen for adults with an identical genotype. One fetus with hydrops fetalis (--/--) and Hb E trait had low beta E and beta A levels which, however, were nearly identical (1.5 and 1.3% of the total hemoglobin). These beta chains apparently combine with the embryonic zeta chain to form Hb Portland-II (zeta 2 beta 2A) and a variant of this hemoglobin (zeta 2 beta 2 E). The affinity of the two beta chains for the zeta chain must be the same and quite different from that for the alpha chain. Moreover, this single observation suggests an equal synthesis of beta A and beta E chains, the low level of Hb E in adult heterozygotes being primarily the result of a greatly decreased rate of assembly of alpha beta E dimers.