The levels of ζ, γ, and δ chains in patients with Hb H disease

Details are given of a study of blood samples from 24 patients with Hb H disease from different Mediterranean countries and from the Far East. Four different types of α-thal-1 (--) were observed, namely-(α) (∼ 20.5-kb deletion);--MED-I (∼ 17.5-kb deletion);--MED-II (>26.5-kb deletion); and--SEA (∼ 18-kb deletion, in Orientals only). The α-thal-2 was mainly of the deletion type (16 with the 3.7-kb deletion; 1 with the 4.2-kb deletion), while 4 of the 7 patients with a nondeletional type had the five-nucleotide deletion at the donor splice site of the first intron of the α2 gene. All patients had a mild-to-moderate hemolytic anemia; no significant differences in hematology were observed between the groups. Hb A₂ was decreased to about one-third of the normal level. The Hb H formation varied considerably and its quantitation was not always satisfactory. Patients with Hb H disease due to any α-thal-1 combined with a nondeletional α-thal-2 had the highest Hb H levels and a more marked anemia. The ζ chain production was small and absent in patients with the MED-II type of α-thal-1 because this deletion included the ζ and ψζ genes. The highest ζ chain levels were present in the four patients with the SEA type of α-thal-1. The γ chain production was increased, particularly in patients with a mutation of C → T at position-158 to the ^Gγ globin gene. This γ chain was primarily present as Hb Bart's (or γ₄) and only about 15% was recovered as Hb F or α₂γ₂. The evaluation of the rate of γ chains produced in these patients was greatly facilitated by data from one patient who had Hb H disease and a heterozygosity for the ^Aγ-β⁺. The low levels of Hb A₂ and of Hb F (relative to Hb Bart's) can be explained by a decreased affinity of α chains for δ and γ chains as compared with β chains in conditions of severe α chain deficiency.