Sickle cell trait
|Sickle cell trait|
|Classification and external resources|
Sickle cells in human blood: both normal red blood cells and sickle-shaped cells are present
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 incompletely dominant). 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 body to produce an abnormal (sickle) shape 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 environments where malaria is present.
Normal haemoglobin is called haemoglobin A, but people with sickle cell disease have only haemoglobin 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 haemoglobin (hemoglobin A, genotype AA). A person with sickle cell trait inherits one normal gene and one abnormal gene encoding haemoglobin S (haemoglobin genotype AS).
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. It has been described in Indians, Middle Easterners (such as Arabs and Iranians), Native American peoples, North Africans, and Turks.
Sickle cell trait is a hemoglobin genotype AS and is generally regarded as a benign condition. 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. There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations. Significance may be greater during exercise.
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.
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.
- Renal medullary carcinoma, a cancer affecting the kidney, is a very rare complication seen in patients with sickle cell trait.
- Probable: complicated hyphema, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia
- Insufficient evidence: retinopathy, cholelithiasis, priapism, 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.
There have been reports of pulmonary venous thromboembolism in pregnant women with sickle cell trait, 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.
Sickle cell trait appears to worsen the complications seen in diabetes mellitus type 2 (retinopathy, nephropathy and proteinuria) and provoke hyperosmolar diabetic coma nephropathy especially in male patients.
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