Alpha-thalassemia is a common inherited blood disorder; approximately 5% of the global population carry a defective alpha-thalassemia gene.[16]Thalassaemia International Federation. Guidelines for the management of alpha-thalassaemia. 2023.[17]Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647473/pdf/06-036673.pdf
http://www.ncbi.nlm.nih.gov/pubmed/18568278?tool=bestpractice.com
The worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role for alpha-thalassemia against the more severe manifestations of malaria.[18]Flint J, Hill AV, Bowden DK, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature. 1986 Jun 19-25;321(6072):744-50.
http://www.ncbi.nlm.nih.gov/pubmed/3713863?tool=bestpractice.com
Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia, and different genetic subtypes have variable frequencies in each of these areas.[19]Association of Public Health Laboratories; Centers for Disease Control and Prevention. Hemoglobinopathies: current practices for screening, confirmation and follow-up. Dec 2015 [internet publication].
https://www.cdc.gov/ncbddd/sicklecell/documents/nbs_hemoglobinopathy-testing_122015.pdf
[20]Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev. 2012 Apr;26(suppl 1):S3-6.
http://www.ncbi.nlm.nih.gov/pubmed/22631040?tool=bestpractice.com
[21]Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet. 2022 Jun 18;399(10343):2310-24.
http://www.ncbi.nlm.nih.gov/pubmed/35691301?tool=bestpractice.com
Alpha(0) variants, important because they can lead to hemoglobin H (Hb H) and alpha-thalassemia major, are most common in Southeast Asia, where the prevalence of carriers reaches 14% in northern Thailand and 5% to 8.8% in southern China.[11]Chui DH, Waye JS. Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem. Blood. 1998 Apr 1;91(7):2213-22.
https://ashpublications.org/blood/article/91/7/2213/261092/Hydrops-Fetalis-Caused-by-Thalassemia-An-Emerging
http://www.ncbi.nlm.nih.gov/pubmed/9516118?tool=bestpractice.com
The nondeletional mutation Hb Constant Spring is also common in Southeast Asia.[22]Jomoui W, Fucharoen G, Sanchaisuriya K, et al. Hemoglobin Constant Spring among Southeast Asian populations: haplotypic heterogeneities and phylogenetic analysis. PLoS One. 2015;10(12):e0145230.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145230
http://www.ncbi.nlm.nih.gov/pubmed/26683994?tool=bestpractice.com
The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. The most common form of alpha(+) thalassemia seen in the US is due to the -alpha(3.7) deletion, a single alpha-globin gene deletion, and is present in approximately 30% of African-Americans.[23]Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005 Jul 15;106(2):740-5.
https://ashpublications.org/blood/article/106/2/740/21345/Hematologic-differences-between-African-Americans
http://www.ncbi.nlm.nih.gov/pubmed/15790781?tool=bestpractice.com
However, even in the homozygous state this disorder will result only in a mild microcytic anemia. The more serious clinical disorders of Hb H and alpha-thalassemia major, although found throughout the US today, are more common in the western US and have dramatically increased in prevalence in the past two decades due to increased Asian immigration.[8]Vichinsky EP, MacKlin EA, Waye JS, et al. Changes in the epidemiology of thalassemia in North America: a new minority disease. Pediatrics. 2005 Dec;116(6):e818-25.
http://www.ncbi.nlm.nih.gov/pubmed/16291734?tool=bestpractice.com