Sickle cell trait
Sickle cell trait (or sicklemia) describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that allele (is homozygous). Those who are heterozygous for the sickle cell allele produce both normal and abnormal hemoglobin (the two alleles are co-dominant). Sickle cell disease is a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance hemoglobin in the red blood cells. Sickling and sickle cell disease also confer some resistance to malaria parasitization of red blood cells, so that individuals with sickle-cell trait (heterozygotes) have a selective advantage in some environments.
Hemoglobin genetics
Normal hemoglobin is called hemoglobin A, but people with sickle cell disease have only hemoglobin S, which turns normal, round red blood cells into abnormally curved (sickle) shapes.
Normally, a person inherits two copies of the gene that produces beta-globin, a protein needed to produce normal hemoglobin (hemoglobin A, genotype AA). A person with sickle cell trait inherits one normal gene and one abnormal gene encoding hemoglobin S (hemoglobin genotype AS).
Prevalence
Sickle cell trait prevalence is highest in West Africa (25% of the population). However, it also very infrequently appears in Mediterranean countries such as Italy, Greece, and Spain, where it most likely expanded via the selective pressure of malaria, a disease that was endemic to the region.[1] It has been described in Indians, Middle Easterners (such as Arabs and Iranians), Native American peoples, North Africans, and Turks.
Symptoms
Sickle cell trait is a hemoglobin genotype AS is generally regarded as a benign condition.[2] However, individuals with sickle cell trait may have rare complications. For example, in November 2010, Dr. Jeffery K. Taubenberger of the National Institutes of Health discovered the earliest proof of Sickle-cell disease while looking for the virus of the 1918 flu during the autopsy of an African-American soldier. Taubenberger autopsy results show that he suffered a sickle-cell crisis that contributed to his death even though he had one copy of the gene.[3] There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations.[4] Significance may be greater during exercise.[5]
Established associations
- Sudden deaths during physical exertion in black US army recruits[13][14]
Suggested
In some cases, athletes with sickle cell trait do not achieve the same level of performance as elite athletes with normal hemoglobin AA. Athletes with sickle cell trait and their instructors must be aware of the dangers of the condition during anaerobic exertion especially in hot and dehydrated conditions.
An association with complicated migraine headaches has been suggested.[17]
There have been reports of pulmonary venous thromboembolism in pregnant women with sickle cell trait,[18] or men during prolonged airflight, mild strokes and abnormalities on PET scans in children with the trait
In rare cases, exercise-induced dehydration or exhaustion can cause healthy red blood cells to turn sickle-shaped, which can cause death during sporting activities.[19]
Sickle cell trait appears to worsen the complications seen in diabetes mellitus type 2 (retinopathy, nephropathy and proteinuria)[20] and provoke hyperosmolar diabetic coma nephropathy especially in male patients.
See also
References
- ^ Ragusa et al. (1992) Presence of an African Beta-globin Gene Cluster Haplotype in Normal Chromosomes in Sicily. Am J Hematol; 40:313-315
- ^ Roach ES (November 2005). "Sickle cell trait: innocent until proven guilty". Arch. Neurol. 62 (11): 1781–2. doi:10.1001/archneur.62.11.1781. PMID 16286558. http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=16286558.
- ^ "From 1918 Autopsy, A First Glimpse of Sickle Cell — and a Warning" www.wired.com
- ^ Ajayi AA (October 2005). "Should the sickle cell trait be reclassified as a disease state?". Eur. J. Intern. Med. 16 (6): 463. doi:10.1016/j.ejim.2005.02.010. ISSN 0953-6205. PMID 16198915.
- ^ Connes P, Reid H, Hardy-Dessources MD, Morrison E, Hue O (2008). "Physiological responses of sickle cell trait carriers during exercise". Sports Med 38 (11): 931–46. doi:10.2165/00007256-200838110-00004. PMID 18937523. http://content.wkhealth.com/linkback/openurl?issn=0112-1642&volume=38&issue=11&spage=931.
- ^ Davis CJ, Mostofi FK, Sesterhenn IA (January 1995). "Renal medullary carcinoma. The seventh sickle cell nephropathy". Am. J. Surg. Pathol. 19 (1): 1–11. doi:10.1097/00000478-199501000-00001. ISSN 0147-5185. PMID 7528470.
- ^ a b Zadeii G, Lohr JW (June 1997). "Renal papillary necrosis in a patient with sickle cell trait". J. Am. Soc. Nephrol. 8 (6): 1034–9. PMID 9189873. http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=9189873.
- ^ Mary Louise Turgeon (2005). Clinical hematology: theory and procedures. Lippincott Williams & Wilkins. pp. 179–. ISBN 9780781750073. http://books.google.com/?id=v2iyQBKx00kC&pg=PA179. Retrieved 6 May 2010.
- ^ Gupta AK, Kirchner KA, Nicholson R, et al. (December 1991). "Effects of alpha-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait". J. Clin. Invest. 88 (6): 1963–8. doi:10.1172/JCI115521. PMC 295777. PMID 1752955. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=295777.
- ^ Amit K. Ghosh (13 June 2008). Mayo Clinic Internal Medicine Review: Eighth Edition. Informa Health Care. pp. 425–. ISBN 9781420084788. http://books.google.com/?id=B7xUKYrnUtMC&pg=PA425. Retrieved 6 May 2010.
- ^ Sheikha A (October 2005). "Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary". Can J Surg 48 (5): 377–81. PMID 16248136. http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/cjs/vol-48/issue-5/pdf/pg377.pdf.
- ^ Betty Pace (2007). Renaissance of Sickle Cell Disease Research in the Genome Era. Imperial College Press. pp. 62–. ISBN 9781860946455. http://books.google.com/?id=mhqswaCtcLQC&pg=PA62. Retrieved 6 May 2010.
- ^ Kark JA, Posey DM, Schumacher HR, Ruehle CJ (September 1987). "Sickle-cell trait as a risk factor for sudden death in physical training" (Free full text). N. Engl. J. Med. 317 (13): 781–7. doi:10.1056/NEJM198709243171301. ISSN 0028-4793. PMID 3627196. http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html.
- ^ Mitchell BL (March 2007). "Sickle cell trait and sudden death--bringing it home". J Natl Med Assoc 99 (3): 300–5. ISSN 0027-9684. PMC 2569637. PMID 17393956. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2569637.
- ^ a b c Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y (June 2009). "Complications associated with sickle cell trait: a brief narrative review". Am. J. Med. 122 (6): 507–12. doi:10.1016/j.amjmed.2008.12.020. PMID 19393983. http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(09)00115-6.
- ^ Birnbaum BF, Pinzone JJ (2008). "Sickle cell trait and priapism: a case report and review of the literature". Cases J 1: 429. doi:10.1186/1757-1626-1-429. PMC 2628646. PMID 19116025. http://www.casesjournal.com/content/1//429.
- ^ Osuntokun BO, Osuntokun O (June 1972). "Complicated migraine and Haemoglobin AS in Nigerians" (Free full text). Br Med J 2 (5814): 621–2. doi:10.1136/bmj.2.5814.621. ISSN 0007-1447. PMC 1788370. PMID 5031686. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1788370.
- ^ Austin H, Key NS, Benson JM, et al. (August 2007). "Sickle cell trait and the risk of venous thromboembolism among blacks" (Free full text). Blood 110 (3): 908–12. doi:10.1182/blood-2006-11-057604. ISSN 0006-4971. PMID 17409269. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=17409269.
- ^ Eichner ER (August 2007). "Sickle cell trait". J Sport Rehabil 16 (3): 197–203. ISSN 1056-6716. PMID 17923725.
- ^ Ajayi AA, Kolawole BA (August 2004). "Sickle cell trait and gender influence type 2 diabetic complications in African patients". Eur. J. Intern. Med. 15 (5): 312–315. doi:10.1016/j.ejim.2004.06.003. ISSN 0953-6205. PMID 15450989.