Theme : Genetic deseases
Sickle-cell disease (SCD) & Malaria
Looking at these maps, can you develop a hypothesis as to the link between Malaria & SCD ? Sickle-cell disease (SCD) is a single gene recessive disorder that involves an abnormality of the hemoglobin (Hgb) molecule. This disorder causes the red cell to sickle under certain circumstances. A sickled cell cannot undergo normal respiratory functions and they interfere with normal blood circulation. Sickle cell disease is genetic and a patient may be homozygous (HbS/HbS) or heterozygous (HbS/HbA). At the genetic level adenine replaces thymine in the codon of chromosome 11. Ultimately the result is Hgb S that polymerizes, gels and precipitates with exposure to hypoxemic conditions. The severity of the gene expression varies among individuals.
Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the genus Plasmodium. Malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. The disease is transmitted by the biting of mosquitos, and the symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later.
Heterozygotes are still able to contract malaria, but their symptoms are generally less severe. Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India, and the Middle East. Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases. The malaria parasite (Plasmodium) has a complex lifecycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cells with defective hemoglobin to rupture prematurely, making the Plasmodium parasite unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle-cell trait (selection for the heterozygote).
How Do People Get Sickle Cell Disease?
What are the symptoms of Sickle Cell Disease? Sickle cell disease prevents oxygen from reaching the spleen, liver, kidneys, lungs, heart, or other organs, causing a lot of damage. Without oxygen, the cells that make up these organs die. For example, the spleen is often destroyed in these patients, leading to some loss of immune function. As a result, these patients often experience frequent infections. The red blood cells of patients with sickle cell disease don't live as long as healthy red blood cells. So people with this disorder often have low red blood cell counts (anemia), which is why this disease is commonly referred to as sickle cell anemia. The hemoglobin molecule (made of alpha and beta globin subunits) picks up oxygen in the lungs and releases it when the red cells reach peripheral tissues, such as the muscles. Ordinarily, the hemoglobin molecules exist as single, isolated units in the red cell, whether they have oxygen bound or not. Normal red cells maintain a basic disc shape, whether they are transporting oxygen or not.
Normal red cells maintain their shape as they pass through the capillaries and release oxygen to the peripheral tissues (upper panel). Hemoglobin polymers form in the sickle rell cells with oxygen release, causing them to deform. The deformed cells block the flow of cells and interrupt the delivery of oxygen to the tissues (lower panel).
Sickle hemoglobin exists as isolated units in the red cells when they have oxygen bound. When sickle hemoglobin releases oxygen in the peripheral tissues, however, the molecules tend to stick together and form long chains or polymers. These rigid polymers distort the cell and cause it to bend out of shape. While most distorted cells are simply shaped irregularly, a few have a cresent-like appearence under the microscope. These cresent-like or "sickle shaped" red cells gave the disorder its name. When the red cells return to the lungs and pick up oxygen again, the hemoglobin molecules resume their solitary existence.
How to prevent from sickle cell crisis ? 1- To avoid low oxygen tension (in altitude for example) 2- To avoid extreme physical exercise 3- To avoid dehydration 4- To avoid alcohol, cold
Is there any drug to cure SCD ? Some types of hemoglobin molecules, such as that found before birth (fetal hemoglobin), block the interactions between the deoxygenated hemoglobin S molecules. All people have fetal hemoglobin in their circulation before birth. Fetal hemoglobin protects the unborn child and newborns from the effects of sickle cell hemoglobin. Unfortunately, this hemoglobin disappears within the first year after birth. One approach to treating sickle cell disease is to rekindle production of fetal hemoglobin. The drug, hydroxyurea induces fetal hemoglobin production in some patients with sickle cell disease and improves the clinical condition of some people.
