Sickle cell trait
Encyclopedia
Sickle cell trait 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.
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).
(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. It has been described in India
ns, Middle Easterners (such as Arab
s and Iran
ians), Native American
peoples, North Africa
ns, and Turks
.
, 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.
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.
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.
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
in the red blood cells. Sickling and sickle cell disease also confer some resistance to malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
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
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that produces beta-globin, a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
needed to produce normal hemoglobin (hemoglobin A
Hemoglobin A
Hemoglobin A or adult hemoglobin is the most common human hemoglobin tetramer, comprising over 97% of the total red cell hemoglobin. It consists of two alpha chains and two beta chains ....
, 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 AfricaWest Africa
West Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries and an area of approximately 5 million square km:-Flags of West Africa:...
(25% of the population
Population
A population is all the organisms that both belong to the same group or species and live in the same geographical area. The area that is used to define a sexual population is such that inter-breeding is possible between any pair within the area and more probable than cross-breeding with individuals...
). However, it also very infrequently appears in Mediterranean countries such as Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
, Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....
, and Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...
, where it most likely expanded via the selective pressure of malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
, a disease that was endemic to the region. It has been described in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
ns, Middle Easterners (such as Arab
Arab
Arab people, also known as Arabs , are a panethnicity primarily living in the Arab world, which is located in Western Asia and North Africa. They are identified as such on one or more of genealogical, linguistic, or cultural grounds, with tribal affiliations, and intra-tribal relationships playing...
s and Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...
ians), Native American
Indigenous peoples of the Americas
The indigenous peoples of the Americas are the pre-Columbian inhabitants of North and South America, their descendants and other ethnic groups who are identified with those peoples. Indigenous peoples are known in Canada as Aboriginal peoples, and in the United States as Native Americans...
peoples, North Africa
North Africa
North Africa or Northern Africa is the northernmost region of the African continent, linked by the Sahara to Sub-Saharan Africa. Geopolitically, the United Nations definition of Northern Africa includes eight countries or territories; Algeria, Egypt, Libya, Morocco, South Sudan, Sudan, Tunisia, and...
ns, and Turks
Turkish people
Turkish people, also known as the "Turks" , are an ethnic group primarily living in Turkey and in the former lands of the Ottoman Empire where Turkish minorities had been established in Bulgaria, Cyprus, Bosnia and Herzegovina, Georgia, Greece, Kosovo, Macedonia, and Romania...
.
Symptoms
Sickle cell trait is a hemoglobin genotype AS is generally regarded as a benign condition. However, individuals with sickle cell trait may have rare complications. For example, in November 2010November 2010
November 2010 was the eleventh month of that year. It began on a Monday and ended after 30 days on a Tuesday.-Portal:Current events:This is an archived version of Wikipedia's Current events Portal from November 2010....
, Dr. Jeffery K. Taubenberger of the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
discovered the earliest proof of Sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
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.
Established associations
- Renal medullary carcinomaRenal medullary carcinomaRenal medullary carcinoma is a rare type of cancer that affects the kidney. It tends to be aggressive, difficult to treat, and is often metastatic at the time of diagnosis...
, a cancer affecting the kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, is a very rare complication seen in patients with sickle cell trait.
- hematuriaHematuriaIn medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
- renal papillary necrosisRenal papillary necrosisRenal papillary necrosis is a form of nephropathy involving the necrosis of the renal papilla, which is supplied by the vasa recta.-Causes:Analgesic nephropathy is a cause of renal papillary necrosis. The damage is cumulative and most patients of renal papillary necrosis would have ingested at...
(only considered "possible" by some sources)
- hyposthenuria
- splenic infarctsSplenic infarctionIn medicine, splenic infarction is a condition in which oxygen supply to the spleen is interrupted, leading to partial or complete infarction in the organ....
at high altitude. Surgery may not always be necessary.
- urinary tract infectionUrinary tract infectionA urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
- Sudden deaths during physical exertion in black US army recruits
Suggested
- Probable: complicated hyphemaHyphemaHyphema is blood in the front chamber of the eye. It may appear as a reddish tinge, or it may appear as a small pool of blood at the bottom of the iris or in the cornea.-Causes:...
, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia
- Possible: acute chest syndromeAcute chest syndromeThe acute chest syndrome is a noninfectious vaso-occlusive crisis of the pulmonary vasculature commonly seen in patients with sickle cell anemia.It is characterized by a new infiltrate on a chest x-ray.-Cause:...
, asymptomatic bacteriuriaBacteriuriaIn medicine, bacteriuria denotes the presence of bacteria in urine not due to contamination from urine sample collection.Urine is normally a sterile bodily fluid when inside the bladder, but can pick up commensals and pathogens when exiting through the urethra...
, and anemia in pregnancy
- Insufficient evidence: retinopathyRetinopathyRetinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
, cholelithiasis, priapismPriapismPriapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...
, leg ulcers, liver necrosis, avascular necrosis of the femoral head, and strokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
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.
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
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
(retinopathy
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
, nephropathy
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
and proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
) and provoke hyperosmolar diabetic coma nephropathy especially in male patients.