Sickle Hemoglobin (Hb S) Allele and Sickle Cell Disease: A HuGE Review

• Published in: American journal of epidemiology 2000-05, Vol.151 (9), p.839-845
• Main Authors: Ashley-Koch, A., Yang, Q., Olney, R. S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Distribution; Alleles; alpha-Thalassemia - epidemiology; alpha-Thalassemia - genetics; anemia; Anemia, Sickle Cell - diagnosis; Anemia, Sickle Cell - epidemiology; Anemia, Sickle Cell - genetics; Anemias. Hemoglobinopathies; Biological and medical sciences; Cardiovascular Diseases - epidemiology; Chest Pain - epidemiology; Child; Child, Preschool; Comorbidity; Diseases of red blood cells; epidemiology; Female; Fetal Hemoglobin - genetics; Genetic Testing - legislation & jurisprudence; Genetic Testing - trends; genetics; Globins - genetics; Haplotypes - genetics; Hb S; Hematologic and hematopoietic diseases; hemoglobin; Hemoglobin, Sickle - genetics; Humans; Infant; Infant, Newborn; Malaria, Falciparum - genetics; Male; Medical sciences; Pneumonia - epidemiology; Prevalence; public health; Sex Distribution; sickle; sickle cell; sickle cell trait; Survival Rate; United States - epidemiology
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/oxfordjournals.aje.a010288

Sickle cell disease is caused by a variant of the β-globin gene called sickle hemoglobin (Hb S). Inherited autosomal recessively, either two copies of Hb S or one copy of Hb S plus another β-globin variant (such as Hb C) are required for disease expression. Hb S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb 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 Hb S. Am J Epidemiol 2000; 151: 839-45.