The Hemoglobin E Syndromes

Abstract

Heterozygotes and homozygotes for HbE (beta 26, GAG-AAG, Glu-Lys) are microcytic, minimally anemic, and asymptomatic. The microcytosis is attributed to the beta thalassemic nature of the beta E gene, whereas the in vitro instability of HbE does not contribute to the phenotype. However, the compound heterozygote state HbE/beta thalassemia results in a variable, and often severe anemia, with the phenotype ranging from transfusion dependence to a complete lack of symptoms. This has been well documented in Thailand, but the basis of the interaction and the cause of the variability remains unexplained. We have studied 50 HbE/beta thalassemics from the UK and 16 from Oakland, CA and assessed the role of HbE instability. Time-course globin chain synthesis experiments have shown that instability is not an important factor in the steady state, but that at 41 degrees C newly synthesized Hb molecules are unstable. We have identified one family in which HbE interacts with pyrimidine 5' nucleotidase deficiency to cause severe anemia with Hb instability. The UK individuals, mostly of Bengali origin, have Hb's from 4.5-11 g/dl. The beta thalassemia mutation, alpha thalassemia and the Xmn 1 G gamma polymorphism do not explain this variability, but the relative and absolute amounts of HbF correlate significantly with total Hb. The Oakland individuals, mostly from Southeast Asia, show similar variation in Hb, which again is largely unexplained.

Determinants of specific RNA interference-mediated silencing of human β-globin alleles differing by a single nucleotide polymorphism

“…However, introducing two bulky mismatched purines at position 10 abrogated silencing. The same observation was made with siRNAs designed to silence another disease-causing allele (␤ E ), which has a codon 26 SNP and produces HbE that is unstable under conditions of oxidative stress and elevated body temperature (13). These findings sug-gest that mismatches at the mRNA cleavage site involving pyrimidines can be accommodated within the catalytic site of the RISC endonuclease Ago2 and lead to mRNA degradation, despite the lack of a base-paired interaction at the active site.…”

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

“…In our study, 44.78 % patients were regularly transfused and 5.22 % underwent splenectomy. In an analysis of 50 British patients (originating in Bangladesh, India, Pakistan and South East Asia) with E-b-thalassemia, Rees et al [11] gives an idea of severity of this condition; 50 % of the patients were regularly transfused and nearly 50 % had required splenectomy. Thus, a lesser number of patients in the present study requiring regular transfusion and splenectomy probably are explained by the phenotypic variations in a comparatively homogenous population.…”

Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency

“…There is also evidence that P5ЈN-1 deficiency can interact with hemoglobin E to produce marked hemolytic anemia, 28 raising the possibility that heterozygosity for P5ЈN-1 deficiency is one of the unidentified factors that contribute to the marked variability seen in HbE/␤ thalassemia and other forms of thalassemia. 29 This possibility can now be investigated by DNA analysis. Previous studies were made difficult by the acquired deficiency of P5ЈN-1 associated with ␤ thalassemia trait.…”