Sickle cell anaemia

Sickle-shaped red blood cells

Sickle cell anaemia (SCA) is a common genetic disease which causes the red blood cells of a sufferer to be shaped like sickles, instead of the normal rounded shape. This causes the cells to become stuck in capillaries which deprives the body of oxygen and causes inflammation. The disease usually occurs in periodic painful attacks, eventually leading to damage of some internal organs, stroke, or anemia, and usually resulting in early death.

Treatment

The first approved drug for the treatment of sickle cell anaemia, hydroxyurea[?], was shown to decrease the number and severeness of attacks in a study in 1995 and shown to increase survival time in a study in 2003. Hydroxyurea had previously been used as a cancer drug, and there is some concern that long-term use may be harmful, but it is likely that the benefits outweigh the risks.

Detailed description and genetics

The gene allele responsible for sickle cell anaemia is incompletely recessive. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the illness and a 1-in-2 chance of their child being a carrier.

The gene defect is a known mutation of a single nucleotide of the beta globin gene. Hemoglobins with this mutation are referred to in the literature as Hb S, as opposed to the more normal adult Hb A. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structure of hemoglobin. What it does allow for, under conditions of low oxygen concentration, is the polymerization of the Hb S itself. In people heterozygous for Hb S (carriers), the polymerization problems are minor. In people homozygous for Hb S, the presence of long chain polymers of Hb S distort the shape of the red blood cell, from a smooth "Lifesaver" shape to a ragged spiky look, making it fragile and susceptible to breaking within capillaries.

The sufferers of the illness usually die early. Still, the disease has not died out. This is because carriers are resistant to malaria. Carriers of the allele have an unsymptomatic condition called Sickle Cell Trait. Since the gene is incompletely recessive, carriers have a few sickle red blood cells at all times but not enough to cause symptoms. Only if they are deprived of oxygen (for example, climbing a mountain) will they develop symptoms.

The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cell to rupture, making the malaria 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 anaemia.

So the illness continues and is especially prevalent among people with recent ancestry in malaria-striken areas, such as Africa, the Mediterranean, India and the Middle East. In fact, sickle-cell anemia is the most common genetic disorder among African Americans; about 1 in every 13 is a carrier.

The evolution of sickle-cell anemia is probably an example of Baldwinian evolution[?], whereby humans modify their environment and thus change the selective pressures. As humans in tropical areas in Africa and elsewhere developed agriculture and animal husbandry, they expanded the niche for mosquitos that could transmit the malaria parasite.

In is interesting that in the USA, where there is no endemic malaria, the incident of sickle-cell anemia amongst people of African descent is much lower than in west Africa and falling. Without endemic malaria, the condition is purely disadvantageous, and will tend to be bred out of the affected population.

Situation of carriers

People who are known carriers of the disease often undergo genetic counselling before they have a child. A test to see if an unborn child has the disease takes either a blood sample from the unborn or a sample of amniotic fluid. Since taking a blood sample from a fetus is dangerous, the latter test is usually used.

After the mutation responsible for this disease was discovered in 1979, the U.S. Air Force required African American applicants to test for the mutation. It dismissed 143 applicants because they were carriers, even though none of them had the condition. It eventually withdrew the requirement, but only after a trainee filed a lawsuit. Now, some insurance companies are doing the same thing to eliminate, in their terminology, 'unwise investments'.

See also: Dominance Relationships, Genetic counselling