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22 - Sickle Cell Trait

from SECTION FIVE - SICKLE CELL DISEASE

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Martin H. Steinberg
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
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Summary

INTRODUCTION

Parents of children with sickle cell anemia seldom have the same disease as their offspring. In 1927, 17 years after the first clinical description of sickle cell anemia, it was discovered that almost 10% of African Americans had erythrocytes that sickled when deoxygenated. With the subsequent identification of HbS, and the observation that patients with sickle cell anemia had predominantly HbS in their hemolysates, whereas their parents' had both HbS and HbA, the genetics of sickle hemoglobinopathies was characterized and sickle cell trait (HbAS) was defined.

Almost 40 years ago, reports of sudden death in military recruits with HbAS triggered a push for mandatory screening for HbAS, denial of military service for some carriers, and insurance coverage cancellation for others. An astounding list of complications of HbAS appeared in the literature. The interpretation of these reports often disregarded the distinction between statistically significant associations and coincidence, and almost all lacked any control comparisons. This chapter reviews what is known, what is presumed, and what is erroneous about the pathogenicity, clinical features, and management of HbAS.

PATHOGENESIS

HbAS is usually implies simple heterozygosity for the HbS gene (HBB glu6val). Less than half the hemoglobin in the HbAS erythrocyte is HbS; the remainder is mainly HbA. The probability that the mixed hybrid tetramer, α2βSβA, will enter the polymer phase is only half that of the HbS tetramer, α2βS2 (Fig. 22.1A).

Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 549 - 563
Publisher: Cambridge University Press
Print publication year: 2009

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