Compound heterozygosity for a mild beta (+) and a rare beta(0)-thalassemia allele

Hematological and hemoglobin composition data are presented for 14 members of a Surinam family (and for 1 unrelated subject) with either a beta-thalassemia heterozygosity [5 with the -29 (A----G) beta + mutation and 5 with the IVS II-849 (A----G) beta(0) mutation] or a compound heterozygosity (the 5 remaining patients). Identification of the mutation was by hybridization of amplified DNA with 32P-labelled synthetic oligonucleotides. The data indicate distinct differences between the two groups of heterozygotes, mainly in degree of microcytosis and hypochromia, in Hb A2 level, and in the level of G gamma (high in the -29 heterozygotes and low in the IVS II-849 heterozygotes). The 5 compound heterozygotes had a thalassemia intermedia with high Hb F levels (high G gamma), elevated Hb A2, and Hb A levels comparable to those seen in patients with a homozygosity for the -29 mutation or with the combination of this beta(+)-thalassemia and Hb S. An alpha-thalassemia-2 heterozygosity (-3.7 kb deletion) was present in 2 patients. Their hematological data were improved over those for the patients with four alpha globin genes; one was the mother of two sets of twins. The high G gamma value in the Hb F of the compound heterozygotes suggests that the high Hb F production in the condition is mainly directed by the chromosome with the -29 (A----G) mutation.