The Pattern of Disordered Haemoglobin Synthesis in Homozygous and Heterozygous β‐Thalassaemia*

Abstract

Summary: The rate of globin chain production has been studied in patients with homozygous β‐thalassaemia, heterozygous β‐thalassaemia, haemoglobin E‐thalassaemia, and sickle‐cell‐thalassaemia, and compared with that in non‐thalassaemic individuals. A partial or total deficit of β‐chain synthesis has been demonstrated in all forms of β‐thalassaemia. This results in the production of a large intracellular pool of α‐chains, the kinetics of which have been worked out. The α‐chains in this pool appear to contain haem and are unstable, rapidly becoming associated with the stromal fraction. These findings are examined in terms of the pathogenesis of the anaemia of thalassaemia.

Defect in hemoglobin synthesis possibly due to a disturbed association

“…These data are in good agreement with those published by Weatherall et al [7] and can be compared The total synthetic ratio shows an unbalanced synthesis for the E-p thalassemic patient. After a 1 hr incubation, the (Y and p chain synthesis is balanced for both heterozygous AE and homozygous E.…”

“…In these latter cases, the total activity ratio OS/o ranged from 0.43 to 0.62 [7-lo], and 31% of the total incorporation was found in 0s chains [7]. Our results can suggest a defective synthesis of 4E chains.…”

“…On the other hand, the excess of labelled fi chains could be explained by the existence of abnormal /. ?E4 tetramers, having the same electrophoretical mobility as hemoglobin E. A large pool of free CY chains has been described in /3-thalassemia [7,11] where 0 chain synthesis is decreased, and in some unstable hemoglobins [ 1 ,121, in relation with an enhanced degradation. The results are not completely explained by a decreased synthesis since we observed an almost balanced synthesis between /_?E and LY chains.…”

Splenic Sequestration and Ineffective Erythropoiesis in Hemoglobin E-β-Thalassemia Disease

“…Nathan and Gunn (23) have demonstrated alterations in membrane permeability as a consequence of unbalanced a chain synthesis in thalassemia. Whole cell lysates from Thai patients with hemoglobin E-P-thalassemia have been shown to have an absence of PA chains with a marked increase in a/PE ratio (32).…”

“…The anemia in hemoglobin E-P-thalassemia is related to 1) ineffective erythropoiesis with unbalanced globin chain synthesis characteristic of thalassemia (32) and spontaneous hemoglobin E oxidation (13), and 2) subsequent sequestration of many of the damaged red cells that escaped from the marrow. This clinical hypersplenism has been documented in Thailand and splenectomies have been performed for this condition over the past 20 years with varying results (30).…”