Genetic basis and clinical manifestations of sickle cell anemia

Sickle cell anemia is a genetic, life-long condition which causes defected red blood cells, which form sickle cell shapes upon becoming deoxygenated, rather than maintaining the usual disc shape. The deformity in shape prevents the red cells from moving easily through the blood vessels as normal cells would. The sickle shaped cells tend to form clumps in the blood vessels and prevent the healthy cells from getting through. These blockages in the vessels may result in pain, serious infection and organ damage to the patient depending on where in the body the clumps form. Sickle cell anemia confers immunity to malaria, and as a result is more prevalent in ethnic groups from areas of the world in which malaria is prevalent (NIH).

GENETICS

Individuals who have sickle cell anemia are born with the condition, and will have the disorder for life as there is no cure. Those who inherit the disorder have two copies of the sickle cell gene, one from each parent. Those who inherit only one sickle cell gene and one healthy gene will develop a condition called sickle cell trait rather than full blown sickle cell anemia. This condition does not result in the same symptoms as sickle cell anemia, and so may go undetected. Those with sickle cell condition are at risk of passing the gene for sickle cell anemia to their children, and if the other parent were to also pass on the gene the child would develop sickle cell anemia (NIH).

MECHANISM

The mutation in sickle hemoglobin S, the hemoglobin specifically found in sickle cell disease, is caused by a substitution of valine for glutamic acid in the sixth position of the ?-hemoglobin chain. This mutation causes the hemoglobin to crystallize when the cell becomes deoxygenated, which is the mechanism causing the hemoglobin molecules to stick together, thus leading to the deformity in the cell shape which is characteristic of the condition (SCIC). These cells clump together as they are sticky and the deformed shape prevents them from moving easily through the blood vessels. The blockages which are caused in the blood vessels lead to anemia as not only are the deformed sickle cells incapable of carrying oxygen, they also prevent healthy oxygenated erythrocytes from reaching the tissues of the body (NIH).

SYMPTOMS sufferer of sickle cell anemia will display the typical symptoms of anemia, which are fatigue, pale skin and nails, jaundice and shortness of breath. This type of anemia is also accompanied by severe episodes of pain due to the blockages in the blood vessels, which are termed sickle cell crises. The frequency of these crises varies between persons. Those who are heterozygous, and therefore only develop sickle cell trait, usually remain symptomless (NIH).

THERAPY

The main problems which will put the patient at risk in sickle cell disease are the sickle cell crises. These are an issue not only to the severe pain which they cause but also due to the damage which the blockage of blood vessels can cause when they occur in or around an organ. Pulmonary complications are a particular problem for sufferers of sickle cell disease, which are caused in this manner. Bacterial infections are also a significant cause of morbidity and mortality in sickle cell sufferers as the function of the spleen is usually either compromised or entirely absent. Splenic sequestration is one of the most serious complications of sickle cell disease, in which the spleen swells and causes a significant drop in hemoglobin levels.

There is no generally accepted cure for sickle cell disease, although in a very small number of patients a bone marrow transplant may rid them of the disease. Therapy focuses on relieving the symptoms associated with the condition. This would include analgesia for pain such as NSAIDs and iron replacement for the effects of the anemia, and in severe cases of the condition blood transfusions may be necessary (NIH). Folate supplements are also given to meet the increased needs for blood cell production. Many sufferers are also advised to undertake occupational therapy and physical therapy to help with pain management. Hydroxyurea is the first drug which has been shown to significantly prevent sickle cell crises, and is therefore indicated daily in treatment (SCIC).