Slow Rate of Haemichrome Formation from Oxidized Haemoglobin Bart's (γ 4 ): A Possible Explanation for the Unequal Quantities of Haemoglobins H (β 4 ) and Bart's in Alpha‐Thalassaemia

S ummary Haemoglobins A, H (β 4 ) and Bart's (γ 4 ) obtained from two adult patients with haemoglobin H and persistent haemoglobin Bart's were separated and eluted from starch block electrophoresis. The spectrum of oxidized haemoglobin Bart's separated from the two patients indicated the presence of a haemichrome. In this respect, the properties of oxidized y‐chains are similar to those of oxidized haem‐bear‐ing α‐chains and haemoglobin H. The rate of haemichrome formation was found to be different for each sub‐unit in the following order α > β > γ > α 2 β 2 . These in vitro observations correlate well with the properties of excess haemoglobin subunits present in vivo in red cells of patients with the thalassaemia syndrome: α‐chains precipitate as inclusion bodies in the bone marrow and β‐chains mainly in peripheral mature red cells while precipitates of γ‐chains have not been identified. On the other hand, γ‐chains are the most stable in a soluble form while α‐chains, even when present in excess, can hardly be detected in a soluble form. In the heterozygote for α‐thalassaemia an average of 6.0% haemoglobin Bart's usually diminishes during the first year without being replaced by a similar amount of haemoglobin H. In haemoglobin H disease large quantities of haemoglobin Bart's are replaced by much smaller amounts of haemoglobin H. Assuming that the genetic defect in α‐chain production is the same in foetal and adult life, the differences in solubility and stability between γ and β‐oxidized chains may explain this phenomenon. Since γ‐chains are stable in their oxidized form, they do not precipitate readily in contrast with β‐chains which form inclusion bodies.