Sickle cell disease (from the Greek drepnos, sickle), also known hemoglobinose S, sicklemia, or sickle cell anemia is a hereditary disease and is characterized by the alteration of hemoglobin, a protein of the transport of oxygen in the blood .
Sickle cell anemia is not a very rare disease. It is particularly common in populations of African sub-Saharan Africa, with a clear predominance in Equatorial Africa (each year 300 000 African children born with this genetic abnormality), but it also exists in North Africa, Greece, Turkey, Saudi Arabia and India. An estimated 50 million people are affected in the world.
This is the first genetic disease in France, and probably in the world.
In 1904, James Herrick, a physician in Chicago, is the first medical description of the disease: it looks at a black student aged 20, hospitalized for fever and cough. The subject is low, has suffered from dizziness and headaches. For a year he felt palpitations and shortness of breath as some members of his family. The blood test shows that the patient is very anemic, the number of red blood cells less than half the normal value. The observation of a blood film shows RBCs unusual sickle-shaped or acanthus leaves.
In 1949, James Neel shows that the transmission of this disease is Mendelian. The same year Linus Pauling showed that it was due to an abnormal structure of hemoglobin, characterized by a lesser solubility. This is the first time we discovered the molecular origin of a genetic disease.
In 1956, the British Vernon Ingram showed that it was due to replacement of an amino acid in the abnormal hemoglobin. This demonstrated for the first time that genes determine the nature of each amino acid in a protein.
In 1978, Tom Maniatis isolated the gene for beta globin.
At the cellular level
Red cells from homozygous, which contain almost exclusively of HbS, acquires the property polymerize when deoxygenation. This explains why the sickling of red blood cells is triggered by lack of oxygen in the blood (hypoxia):
* In vivo, in the venous and capillary blood: hence prolonged sequestration, thrombosis formation and hemolysis of red blood cells easily in the hair for drepanocytes which are struggling to cut a passage, because of their elongated shape and in the slow rate of movement creates the conditions for the formation of drépanocytes, which will be swallowed up by the SRE.
* In vitro, during the examination of fresh blood between slide and coverslip, when a body is added reductant (metabisulfite).
At the molecular level
The gene S is an abnormal allele of the gene governing the structure of the beta chain of hemoglobin. He is responsible for the synthesis of beta chains with a glutamic acid residue in position 6 is replaced by a valine residue. The hemoglobin that results called HbS (Hb S Sickle-cell disease, English name of the disease) has the structure alpha2ß2S. It differs from hemoglobin A, Standard, for its slower electrophoretic mobility, but mostly by the insolubility desoxygenea its form, which crystallizes easily. This form of long fibers that are distorting the red blood cells.
At the genetic level
This is the gene that encodes the beta chain of hemoglobin that is involved. This gene is carried by chromosome 11. The mutated version (allele S) of this gene is responsible for sickle cell anemia. It is a recessive allele: it requires that two copies of this gene is mutated so that the individual is sick. Thus, an individual can not be achieved if both parents have sent him allele (S) responsible, it is said homozygous (S / S).
In heterozygous (S / A), red blood cells contain a mixture in equal proportions of HbA and HbS. During the test deoxygenation between slide and coverslip, these red cells do not take the shape of sickles, but of holly leaves.
Red blood cells have lost their elasticity will clog capillaries, causing ischemia by lack of oxygen at different territories. This explains the painful crises (bone infarction), stroke. Red blood cells may also damage the lining of vessels (endothelium), causing a risk of obstruction of the latter.
These red cells are more fragile and will break more easily, explaining the type of hemolytic anemia (red blood cell destruction).
The S allele, head of the anomaly is most prevalent in the African continent (reaching in some populations the frequency of 30%) is found also in other regions of the Mediterranean Sea, particularly in Italy (especially Sicily), Greece and Anatolia.
This distribution overlaps quite well with that of another disease, malaria or malaria, which has an infectious origin: Plasmodium falciparum.
The high presence of this disease in Africa appears to be a case of balanced genetic polymorphism caused by natural selection: in fact, people healthy heterozygotes (A / S) or with homozygous sickle cell disease (S / S) are protected from disease Neurological Plasmodium, the malaria parasite also known as malaria. Over generations, individuals carriers of S allele were thus reproduced more than others, resulting in increased frequency of this allele.
The disease is reported in infants, but is not usually evident at birth because the red cells of newborns still contain 50-90% fetal hemoglobin. The symptoms of this disease can appear as young as six months. The usual acute manifestations of sickle cell disease are of three kinds:
* Vaso-occlusive Crises: clots clog an artery, causing sudden and severe pain in one part of the body (often the hands, feet, hips, abdomen). These crises can be very painful.
* Hemolytic anemia: red blood cells of sickle cell disease are abnormal. These take a form of sickle, and shall be decided by the filter represents the spleen, where they are destroyed. This destruction leads to a decrease in the number of erythrocytes and thus a regenerative anemia.
* Infections: they are more common in sickle cell disease, especially pneumonia in young children. They can also aggravate anemia in cases of infection with parvovirus B19.
The chronic manifestations of sickle cell disease involve a delay of size and weight, nutritional deficiencies (including folate, because this vitamin is essential to the creation of red blood cells which are repeated very rapidly during the crisis of anemia, thus depleting the stock of folate), a frequent delayed puberty, abnormal cardiopulmonary (increase the size of the heart, respiratory failure), an increased rate of volume (but which over time will decline until it becomes smaller by atrophy), the retinal abnormalities (bleeding), etc..
The destruction of erythrocytes in the spleen leads to vessel occlusion of the latter, partly to blame for the increase in the size of it (splenomegaly). Over time, the rate can no longer fulfill its role as a lymphoid organ (we speak of functional asplenia), resulting in increased sensitivity to some germs, including meningococcal (Neisseria meningitidis) and pneumococcal (Streptococcus pneumoniae).
Examination and diagnosis
Apart from the findings common to all hemolytic anemia, the diagnosis is based on the detection of hemoglobin S. This can be done:
* By the microscopic observation of fresh blood stored between blade and slide, with or without the addition of a reducing agent (potassium metabisulfite, ascorbic acid): you will see the red cells from homozygous turn into sickles and those of the 'heterozygous leaf holly (crystallization of hemoglobin S deform the membrane),
* By electrophoresis of the hemolysate of red blood cells show that, in the homozygote, a single band of a hemoglobin migrating abnormally slowly, and in the heterozygous presence of two bands of hemoglobin, which is faster hemoglobin A and hemoglobin S. other
* Today, tests can detect carriers (people who have the heterozygous allele but are not sick), they are then informed that the child conceived by two carriers has a risk of being out of four suffering from sickle cell anemia.
In industrialized countries, the diagnosis is done in neo-natal period when parents are at risk or suffering. In non-industrialized countries, the diagnosis is often the first manifestation or complication. Neo natal screening could result in an improved prognosis.
The treatment of sickle cell disease is based on:
* The treatment of vaso-occlusive crises: analgesics (opioids may go up) and under oxygen;
* The prevention of crises triggers (cold, altitude, infections, dehydration);
* Folate supplementation;
* The preventive treatment of pneumococcal infections and meningitis;
* Blood transfusions in cases of profound anemia or severe infection.
Hydroxyurea can promote the production of fetal hemoglobin, usually formed in small quantities and perfectly functional, inhibiting the production of red blood cells containing hemoglobin S. This drug appears to reduce significantly the number of painful crises and mortality of the disease. It can not be used because of its mechanism of action, in patients anemic. Monitoring of blood must be very careful. The other obstacle to its use is its cost, which may generate savings of care in the economically developed countries.
The prevention of pneumococcal infections in young children is through vaccination.
Blood transfusions may decrease the risk of cerebral-vascular accidents in some children at high risk (abnormal trans-cranial Doppler).
Simple measures of prevention
To avoid the crises it is recommended to follow the following simple measures:
* Drink water frequently
* Ventilate the rooms, fresh air in order to
* Keep warm
* Do not gain weight
* Eat foods rich in iron, or facilitate the assimilation of iron (red meat, pate...)
* Not catches, or more generally to avoid possible respiratory infections
* Wear clothes that do not cut the blood
* Keep up the pace
* Avoid going over 1500 meters(SONY)
Read also Leukemia