Defect in hemoglobin synthesis possibly due to a disturbed association

Pagnier, J.; Wajcman, Henri; Labie, Aominique

doi:10.1016/0014-5793(74)80855-0

Cited by 11 publications

(5 citation statements)

References 12 publications

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“…The similar level of /JE synthe sis in immature erythroblasts and in reticulo cytes suggests that the /?E mRNA is not unstable as found for the h or Lepore globin mRNA. The results, like those of others in the literature [10,21], indicate clearly that Hb E is not an .unstable hemoglobin but probably a hemoglobin synthesized at a re duced rate; it could be tentatively classified as a moderate thalassemic allele. The com bination of two thalassemic alleles, one to tally deficient (/?°) and the other partially deficient (/?E), could explain the clinical se verity of the association /?°-thal/Hb E.…”

Section: Discussionsupporting

confidence: 72%

Beta°-Thalassemia/Hb E Association

Testa¹,

Dubart²,

Hinard³

et al. 1980

Acta Haematol

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Hemoglobin synthesis in a 34-year-old man of Laotian ancestry with Hb E/β°-thalassemia was studied. Hemoglobin electrophoresis exhibited only Hb F and Hb E. Reticulocytes and bone marrow cells showed no Hb A synthesis. The proportion of Hb F increased (from 14 to 50%) with the density of RBCs fractionated on a discontinuous gradient of Stractan. Reticulocytes were also heterogeneous with regard to their density and their Hb F synthesis: the proportion of Hb F synthesis increased with their density. Fractionation of bone marrow cells by density on a discontinuous gradient of Stractan provided populations of cells at different stages of maturation, the more mature having the greater density. Study of hemoglobin synthesis in bone marrow cells indicated that the proportion of γ-chains synthesized increased and the pool of free α-chains decreased with erythroblast maturation; in contrast, the proportion of βE-chains compared to α-chain synthesis remained constantly low. These results provide evidence that the increased amount of Hb F found in the blood of the patient was mostly due to the positive selection, in bone marrow and in peripheral blood, of cells containing Hb F. In contrast, colonies of early erythroid precursors derived from the blood of the patient exhibited an enormous reactivation of Hb F synthesis in culture. The low proportion of βE-chain synthesis (about 30% of α-chain synthesis) remained unchanged during the erythroid maturation of most immature erythroblasts to reticulocytes. The combination of two thalassemic alleles, one totally deficient (β°) the other partially deficient (βE), can explain the clinical severity of the association β⁰-thalassemia/Hb E.

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Section: Discussionsupporting

confidence: 72%

Beta°-Thalassemia/Hb E Association

Testa¹,

Dubart²,

Hinard³

et al. 1980

Acta Haematol

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“…However, for the purpose of our study, which seeks to clarify the clinical and hematologic features of the homozygous state, her benign clinical findings cannot logically be the bases both for defining the expressions of hemoglobin E honiozygosity and for designating her a homozygote. The same consideration has led us to exclude, for the purpose of this analysis, the presumed homozygote studied by Pagnier et a1 [32] , an Indonesian woman with a venous hemoglobin concentration of 12.5 gm/dl, for whom no pedigree data were available.…”

Section: Discussionmentioning

confidence: 98%

“…In con- [39] Feldman and Rieder [2] Normal Hb EPO-thal Hb E-pO-thal Pagnier e t a1 [32] Hb E trait Hb E homozygote (presumed) Ruymann et al [40] Hb E-pO-thal Friedman et al [41] p+-Thal trait trast, Weatherall et a1 [39] found a/P synthesis ratios of 3.6 and 3.7 in two cases of hemoglobin E-Po-thalassemia, values very similar t o those that they observed in P+-thalassemia major and approximately three times the normal a/P synthesis ratios. Similar results were reported by Pagnier et a1 [32] . As shown in Table V, studies of globin synthesis have given strikingly variable results in hemoglobin E-related disorders and even in normal subjects.…”

Section: Discussionmentioning

confidence: 99%

Homozygous hemoglobin E mimics β‐thalassemia minor without anemia or hemolysis: Hematologic, functional, and biosynthetic studies of first north American cases

et al. 1980

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A young American woman of Thai ancestry living in Ohio and a man of Vietnamese origin living in Iowa are believed to be the first recognized hemoglobin E homozygotes residing in the western hemisphere. Both were clinically well and exhibited neither pallor nor icterus nor splenomegaly. Their blood exhibited marked microcytosis and mild erythrocytosis. Hemoglobin was 99% E and 1% F, 97% E and 3% F, respectively. These features were similar to those previously reported from Southeast Asia and Madagascar in the few well-documented reports of homozygous hemoglobin E. A 51Cr erythrocyte survival study indicated a normal t1/2 of 28 days. Also demonstrated were minimal decrease in whole blood O2 affinity and increased ratio of alpha/non-alpha globin chain synthesis. Mild hemolytic anemia is not, as usually stated, a feature of this condition, which closely mimics a very mild thalassemia minor. Anemia, when found with high proportions of hemoglobin E, should not be attributed to the homozygous hemoglobinopathy. Persons with homozygous hemoglobin E should be reassured as to its benign implications.

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“…Double heterozygosity for Hb E and p-thalassemia is frequently associated with a moderately severe ,p-thalassemia syndrome, the molecular basis of which has not been well defined (2)(3)(4)(5). It has been suggested that the thalassemia-like phenotype of Hb E disorders results from impaired synthesis of iE_globin (6)(7)(8)(9)(10), or, perhaps from I3E_globin chain instability (11,12). Either mechanism could result in a limited supply of the abnormal f8-globin chain and lead to decreased net accumulation of Hb E. To define more precisely the pathogenesis of Hb Table I.…”

Section: Introductionmentioning

confidence: 99%