Valine b113(G15) is an internal residue located in the a1b1 interface (Fig. 3). In deoxyHb it is in molecular contact with Val 23, Glu 26, Ala 27 and Arg 30 of the same chain, and with Ala 110 and Phe 117 of the a1 chain [4]. Valine b113 is replaced by a glutamic acid in Hb New York [5], which is mildly unstable and has a slightly decreased oxygen affinity [6]. The presence of Hb Champagne could explain the mild anemia of the patient, but this hypothesis certainly needs to be strengthened by further functional studies and the report of other cases with the same substitution.

Variants such as Hb Champagne, with electrophoretically neutral substitutions, may be difficult to identify. Theoretically the change from a valine to a leucine residue should not modify the electrophoretic mobility. Six variants of this kind have been reported in the b chain, and the electrophoretic and chromatographic properties of four of these could be compared in our laboratory (Table 1). As expected, they are completely silent in cellulose acetate electrophoresis and during electrophoresis of the globin chains at acid and alkaline pHs. Slight differences in IEF, as compared to Hb A, were observed in Hbs Champagne, Nantes [b34(B16)Val®Leu] (H. Wajcman et al., personal communication), and Johnstown [b109(G11)Val®Leu]. This could be explained by a structural modification of the protein structure changing the exposure of some charged residue; a glutamic acid and an arginine are indeed in contact with this residue. Substitution of a leucine for a valine clearly increases the hydrophobicity, but according to the affected region of the Hb molecule, the results obtained by UT-PAGE, or by reversed phase HPLC differ from one case to another. To detect and characterize such variants a multi-parametric approach may be useful.

New Hb variants must always be reported to determine the degree to which they are responsible for even a mild hematological disorder that may possibly interact with another RBC abnormality [3].