Sickle hemoglobin (Hb S) allele and sickle cell disease: A HuGE review

Abstract

Sickle cell disease is caused by a variant of the β-globin gene called sickle hemoglobin (Hq S). Inherited autosomal recessively, either two copies of Hq S or one copy of Hq S plus another β-globin variant (such as Hq C) are required for disease expression. Hq S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hq S in individuals of African and Mediterranean ancestry. Despite this advantage, individuals with sickle cell disease exhibit significant morbidity and mortality. Symptoms include chronic anemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections. Pediatric mortality is primarily due to bacterial infection and stroke. In adults, specific causes of mortality are more varied, but individuals with more symptomatic disease may exhibit early mortality. Disease expression is variable and is modified by several factors, the most influential being genotype. Other factors include β-globin cluster haplotypes, α-globin gene number, and fetal hemoglobin expression. In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hq S.