Rapid postsynthetic destruction of unstable haemoglobin Bushwick

Abstract

MOST structural variants of human haemoglobin occur in smaller amounts than HbA in the peripheral blood of heterozygous subjects. Abnormal haemoglobins with mutations in the β chain usually comprise 35–45% of the haemoglobin in haemolysates. In contrast, haemoglobins with abnormal α chains generally amount to only 20–25% of the total haemoglobin. This difference in the proportion of α and β chain variants is thought to reflect the fact that in some populations there are two α loci and only one out of four α globin genes is affected in a heterozygote, whereas one out of two β globin alleles is abnormal in a subject with a β varient^1,2. Certain unstable haemoglobins with critical alterations in β-chain structure also constitute a much smaller proportion of the total circulating haemoglobin than HbA. The low concentration of these abnormal haemoglobins is the result of accelerated preferential destruction^3–7. We report here a new unstable β variant, Hb Bushwick, which was detected in an intact form constituting only 1–2% of the total circulating haemoglobin. Evidence was found for rapid postsynthetic destruction of the abnormal β chain. In spite of this accelerated loss of the product of one of the two β alleles, the affected erythrocytes contained normal amounts of haemoglobin.