This article is about the genetic transmission of sickle-cell diseases. For the disease itself, see sickle-cell disease.
| Sickle cell trait |
| Classification and external resources |
|
Sickle cells in human blood: both normal red blood cells and sickle-shaped cells are present
|
| ICD-10 |
D57.3 |
| ICD-9 |
282.5 |
| OMIM |
603903 |
| MedlinePlus |
000527 |
| eMedicine |
topic list |
| MeSH |
D012805 |
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 codominant with respect to the actual concentration of hemoglobin in the circulating cells).
Sickle cell disease is a blood disorder in which there is a single amino acid substitution in the hemoglobin protein of the red blood cells, causing the red blood cells to assume a sickle shape, especially when under low oxygen tension. 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 environments where malaria is present.
Contents
- 1 Hemoglobin genetics
- 2 Prevalence
- 3 Symptoms
- 4 Association with malaria
- 4.1 Established associations
- 4.2 Suggested
- 5 See also
- 6 References
Hemoglobin genetics
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).
The sickle cell trait can be used to demonstrate the concepts of co-dominance and incomplete dominance. An individual with the sickle cell trait shows incomplete dominance when the shape of the RBC is considered. This is because the sickling only happens at low oxygen concentrations. With regards to the actual concentration of hemoglobin in the circulating cells, the alleles demonstrate co-dominance as both 'normal' and mutant forms co-exist in the blood stream. It is interesting to note that unlike the sickle-cell trait, sickle cell disease is passed on in a recessive manner. [1]
Prevalence
Sickle cell trait prevalence is highest in West Africa (25% of the population). It also has a high prevalence in South and Central Americans, especially those in Panama. 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.[2] It has been described in Indians, Middle Easterners (such as Arabs and Iranians), Native American peoples, North Africans, and Turks.[citation needed]
Symptoms
Sickle cell trait is a hemoglobin genotype AS and is generally regarded as a benign condition.[3] 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.[4] There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations.[5] Significance may be greater during exercise.[6]
Association with malaria
Sickle cell trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic. The trait is known to cause significantly fewer deaths due to malaria, especially when Plasmodium falciparum is the causative organism. This is a prime example of natural selection, evident by the fact that the geographical distribution of the gene (for hemoglobin S) and the distribution of malaria in Africa virtually overlap. Because of the unique survival advantage, people with the trait increase in number as more people infected with malaria and having the normal hemoglobin tend to succumb to the complications.
Although the precise mechanism for this phenomenon is not known, a several factors are believed to be responsible.
- Infected erythrocytes (Red Blood cells) tend to have lower oxygen tension, because it is significantly reduced by the parasite. This causes sickling of that particular erythrocyte, signalling the phagocytes to get rid of the cell and hence the parasite within.
- Since the sickling of parasite infected cells is higher, these selectively get removed by the reticulo-endothelial system, thus sparing the normal erythrocytes.
- Excessive vacuole formation occurs in those parasites infecting sickle cells.
- Sickle trait erythrocytes produce higher levels of the superoxide anion and hydrogen peroxide than do normal erythrocytes, both are toxic to malarial parasites.[7]
The sickle cell trait was found to be 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria.[8]
Established associations
- Renal medullary carcinoma, a cancer affecting the kidney, is a very rare complication seen in patients with sickle cell trait.[9]
- renal papillary necrosis[10] (only considered "possible" by some sources)[11]
- splenic infarcts at high altitude.[13] Surgery may not always be necessary.[14]
- urinary tract infection[15]
- Sudden deaths during physical exertion in black US army recruits[16][17]
Suggested
- Probable:[18] complicated hyphema, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia
- Possible:[18] acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy
- Insufficient evidence:[18] retinopathy, cholelithiasis, priapism,[19] leg ulcers, liver necrosis, avascular necrosis of the femoral head, and stroke
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.[20]
An association with complicated migraine headaches has been suggested.[21]
There have been reports of pulmonary venous thromboembolism in pregnant women with sickle cell trait,[22] 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 may cause healthy red blood cells to turn sickle-shaped, which can cause death during sporting activities.[23]
Sickle cell trait appears to worsen the complications seen in diabetes mellitus type 2 (retinopathy, nephropathy and proteinuria)[24] and provoke hyperosmolar diabetic coma nephropathy especially in male patients.
See also
- Ryan Clark (American football)
References
- ^ http://www.ncbi.nlm.nih.gov/books/NBK21226
- ^ Ragusa, A.; et al. (1992). "Presence of an African β-globin Gene Cluster Haplotype in Normal Chromosomes in Sicily". Am J Hematol 40 (4): 313–315. doi:10.1002/ajh.2830400413. PMID 1503087.
- ^ 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.
- ^ "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.
- ^ "Malaria and the Sickle hemoglobin gene". Brigham and Women's Hospital (BWH).
- ^ Williams TN, Mwangi TW, Wambua S, Alexander ND, Kortok M, Snow RW, Marsh K, Kenya Medical Research Institute, Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi District Hospital, Kilifi, Kenya. "Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases". The National Center for Biotechnology Information (NCBI). PMID 15942909.
- ^ 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.
- ^ Mary Louise Turgeon (2005). Clinical hematology: theory and procedures. Lippincott Williams & Wilkins. pp. 179–. ISBN 978-0-7817-5007-3. 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.
- ^ Amit K. Ghosh (13 June 2008). Mayo Clinic Internal Medicine Review: Eighth Edition. Informa Health Care. pp. 425–. ISBN 978-1-4200-8478-8. 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. PMC 3211898. PMID 16248136.
- ^ Betty Pace (2007). Renaissance of Sickle Cell Disease Research in the Genome Era. Imperial College Press. pp. 62–. ISBN 978-1-86094-645-5. 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Tripette, J Et Al. "Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise.". US National Library Of Medicine. PMID 20581085.
- ^ 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.
- ^ 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.
- ^ 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.
|
Pathology: hematology, hematologic diseases of RBCs and megakaryocytes / MEP (D50-69,74, 280-287)
|
|
Red
blood cells |
| ↑ |
|
|
| ↓ |
| Anemia |
| Nutritional |
- Micro-: Iron deficiency anemia
- Macro-: Megaloblastic anemia
|
|
Hemolytic
(mostly Normo-) |
| Hereditary |
- enzymopathy: G6PD
- glycolysis
- hemoglobinopathy: Thalassemia
- Sickle-cell disease/trait
- HPFH
- membrane: Hereditary spherocytosis
- Minkowski-Chauffard syndrome
- Hereditary elliptocytosis
- Southeast Asian ovalocytosis
- Hereditary stomatocytosis
|
|
| Acquired |
- Drug-induced autoimmune
- Drug-induced nonautoimmune
- Hemolytic disease of the newborn
|
|
|
Aplastic
(mostly Normo-) |
- Hereditary: Fanconi anemia
- Diamond–Blackfan anemia
- Acquired: PRCA
- Sideroblastic anemia
- Myelophthisic
|
|
| Blood tests |
- MCV
- Normocytic
- Microcytic
- Macrocytic
- MCHC
|
|
|
| Other |
- Methemoglobinemia
- Sulfhemoglobinemia
- Reticulocytopenia
|
|
|
|
Coagulation/
coagulopathy |
| ↑ |
Hyper-
coagulability |
- primary: Antithrombin III deficiency
- Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden
- Prothrombin G20210A
- Sticky platelet syndrome
- acquired:Thrombocytosis
- DIC
- Congenital afibrinogenemia
- Purpura fulminans
- autoimmune
|
|
|
| ↓ |
Hypo-
coagulability |
| Thrombocytopenia |
- Thrombocytopenic purpura: ITP
- TM
- TTP
- Upshaw Schulman Syndrome
- Heparin-induced thrombocytopenia
- May-Hegglin anomaly
|
|
| Platelet function |
- adhesion
- aggregation
- Glanzmann's thrombasthenia
- platelet storage pool deficiency
- Hermansky–Pudlak syndrome
- Gray platelet syndrome
|
|
| Clotting factor |
- Hemophilia
- von Willebrand disease
- Hypoprothrombinemia/II
- XIII
- Dysfibrinogenemia
|
|
|
|
|
|
|
cell/phys (coag, heme, immu, gran), csfs
|
rbmg/mogr/tumr/hist, sysi/epon, btst
|
drug (B1/2/3+5+6), btst, trns
|
|
|
|