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The Hemoglobin E Syndromes
Author(s) -
REES D. C.,
STYLES L.,
VICHINSKY E. P.,
CLEGG J. B.,
WEATHERALL D. J.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10490.x
Subject(s) - microcytosis , thalassemia , asymptomatic , heterozygote advantage , hemoglobinopathy , medicine , compound heterozygosity , hemoglobin e , phenotype , hemolytic anemia , chemistry , microbiology and biotechnology , genetics , biology , allele , anemia , gene , iron deficiency
A bstract : Heterozygotes and homozygotes for HbE (β26, GAG‐AAG, Glu‐Lys) are microcytic, minimally anemic, and asymptomatic. The microcytosis is attributed to the β thalassemic nature of the β E gene, whereas the in vitro instability of HbE does not contribute to the phenotype. However, the compound heterozygote state HbE/β 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/β 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°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 β thalassemia mutation, α thalassemia and the Xmn 1 Gγ 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.