Homozygous state for Hb constant spring (slow moving Hb X components)

Abstract

A 12 yr old Malay boy who was studied because his youngest brother and both his parents had the slow moving Hb X components (earlier reported to lead to Hb H disease when combined with α thalassemia) was found to be homozygous for the same slow moving components. He had splenomegaly and a just palpable liver, mild anemia with microcytosis, hypochromia, slight morphologic changes of the red blood cells, and slight reticulocytosis. Of 8 children in the family, 6 had the trait for the abnormality, 1 was normal, and 1, the propositus, was homozygous. Structural studies of the isolated abnormal hemoglobin showed it to be identical to Hb Constant Spring (Hb CoSp), an α chain variant with 172 residues instead of the usual 141, the additional 31 being attached to the C terminal end. In addition to the abnormal α variant for which the propositus was homozygous, he also had normal Hb A and normal Hb A2 with normal α chains. If the theory that Hb CoSp is due to a structural mutation affecting the terminator codon is correct, this case provides evidence for a duplication of the gene for α chain production. Results of study of several erythrocyte enzymes are also reported.