HB ARTA [BETA-45 (CD4) PHE-]CYS] - A NEW UNSTABLE HEMOGLOBIN WITH REDUCED OXYGEN-AFFINITY IN TRANS WITH BETA-THALASSEMIA

The interaction of rare Hb variants with beta degrees-thalassaemia res ults in a quasihomozygous state where the erythrocytes contain the var iant as the only major adult Hb component, Such a situation is a uniqu e model that enables functional studies even in the case of a neutral variant that could not be isolated from Hb A, We report here an unusua l patient carrying Hb Arta, a novel Hb variant [beta 45 (CD4) Phe --> Cys], in trans with beta degrees-thalassaemia gene (beta degrees 39). The aminoacid substitution at the critical CD corner of this Hb molecu le renders the molecule unstable. In addition, haem is displaced in a position that favours the deoxy (T) conformation of the variant, but l ess than in Hb Cheverly [beta 45 (CD4) Phe --> Ser], and results in a p50 of 43 mmHg (pH 7.4, 37 degrees C) in the red cells with preservati on of cooperativity. Solution studies of the almost pure Hb Arta show a 50% decrease in oxygen affinity and normal cooperativity; the Bohr e ffect and the interaction with organic phosphates are similar to those of Hb A. Hb Arta retains both normal homo- and heterotropic effects a llowing a well-preserved oxygen transport in vivo despite a mild anaem ia.