INTERACTION OF HEMOGLOBIN-E AND PYRIMIDINE 5'-NUCLEOTIDASE DEFICIENCY

A Bangladeshi family is described in which the genes for both hemoglob in E (Hb E) and pyrimidine 5' nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemol ytic anemia, whereas family members who are homozygous for Hb E are as ymptomatic and those homozygous for pyrimidine 5' nucleotidase deficie ncy have the mild hemolytic anemia that is characteristic of this diso rder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked de crease in the stability of Hb E in pyrimidine 5' nucleotidase-deficien t red blood cells (RBCs), It has also been found that in the enzyme-de ficient RBCs in which Hb E is highly unstable, free alpha-chains, thou gh not beta(E)-chains, accumulate on the membrane. In view of the incr easing evidence that the hemolysis associated with pyrimidine 5' nucle otidase deficiency results not only from an increase in the level of e rythrocyte pyrimidines, but also from inhibition of the hexose monopho sphate shunt activity in young erythrocytes, it is likely that the mar ked instability of Hb E in the enzyme-deficient cells results from oxi dant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the p athophysiology of Hb E/beta-thalassemia, globally the commonest import ant form of thalassemia. (C) 1996 by The American Society of Hematolog y.