Factors That Influence Sickle Cell Disease

Sickle cell disease is quite variable in itself. We know of only a few of the factors that contribute to this variability. Some are genetic. Others likely involve environmental influences. One of the most important genetic factors is thalassemia. One form of thalassemia, called b-thalassemia, reduces the production of normal haemoglobin.

A person with one normal haemoglobin gene and one thalassemia gene has thalassemia trait (also called thalassemia minor). Should one parent have sickle cell trait and the other have thalassemia trait, any child they conceive has one chance in four of receiving one gene for sickle cell disease and one gene for b-thalassemia. This condition is called sickle b-thalassemia. The severity varies.

Some patients with sickle b-thalassemia have a condition as severe as sickle cell disease itself. Others have few and relatively mild problems. The gene for thalassemia is very common among people of Mediterranean origin. The sickle gene also exists in people of Mediterranean origin, although its frequency is much lower than that for thalassemia. People of, say, Greek or Italian background who have a sickle condition most often have sickle b-thalassemia.

Another haemoglobin disorder that interacts with sickle cell disease is haemoglobin C. The abnormal haemoglobin C protein is relatively harmless. People with two haemoglobin C genes have a relatively mild clinical condition termed “haemoglobin C disease”. When haemoglobin C combines with haemoglobin S, the result is “haemoglobin SC disease”. On average, haemoglobin SC disease is milder than sickle cell disease.

However, some patients with haemoglobin SC disease have a clinical condition as severe as any with sickle cell disease. The reason for the marked variability in the clinical course of haemoglobin SC disease is unknown. We do know that the tendency of haemoglobin C to produce red cell dehydration is a major reason that the combination of haemoglobins S and C is so problematic.