Sickle cell disease or disorder is an inherited condition in which there is an abnormality in the haemoglobin.  Haemoglobin is the red pigment in the blood.  It is contained in the red blood cells (erythrocytes).  It takes up oxygen from the air in the lungs and transports it to the tissues where the oxygen is used in metabolic processes to produce energy.  The waste product of this is carbon dioxide, which is taken up by the haemoglobin and transported back to the lungs where it leaves the body in expired air. 

These are essential processes for life.

Pathogenesis
The haemoglobin molecule contains four protein / globin strands: two alpha and two beta around an Iron atom.  Protein is made up of chains of amino acids.  In the beta chain in position 6 in normal adult haemoglobin, the amino acid is glutamic acid.  In sickle haemoglobin the amino acid in this position is valine instead of glutamic acid.  This changes the characteristics of the haemogllobin molecule and causes the haemoglobin to precipitate from solution under acid conditions or conditions of low oxygen. 

The red blood cells are shaped like a doughnut and are wider than the capillaries, which they must pass through in order to transfer the oxygen and carbon dioxide to and from the tissues.  The discrepancy in size ensures that the passage through the capillaries is slow to give enough time for the transfer of gasses to take place.  When haemoglobin precipitates then the red cells are unable to be deformed and cannot pass through the capillaries and blood flow and the transfer of gasses does not occur.  This causes all the medical problems of sickle cell disease. The sickle gene is present in 10% of Jamaicans and 8% of African Americans.

Inheritance
The gene for sickle cell is inherited as an autosomal recessive, which means one gene is given by each parent and may be designated as the “S” gene.  The normal gene for adult haemoglobin is called the “A” gene.  Someone who inherited S genes from both parents has the composition SS and is known as Homozygous and has the full-blown disease. 

Anyone who inherit an S gene and an A gene are designated  ”AS” and is described as having the trait.  These persons have a milder form of the condition and often go through life without any knowledge of the condition.  

There is another abnormal variant of haemoglobin called haemoglobin C / HbC  in which lysine is substituted for glutamic acid in the same position 6 on the beta globulin chain.  These persons are described as having haemoglobin C.   Some persons inherit Hb C from one parent and Hb S from the other parent and are described as having “Hb SC”, yet another variant of the sickle cell disorder.  These have a generally milder form of the disease but are more prone to develop eye complications of the disease. 

Still other persons inherit another condition called thallasaemia in which the haemoglobin is normal but is produced in reduced quantities.  These persons, if they also inherit the sickle gene can have symptoms and constitute another variant of the sickle disorders called sickle thallasaemia. 

Here we have explained four variants of the sickle disorder: SS homozygous condition; AS the trait; SC sickle cell C disorder; and S thal the sickle thallasaemia.

Medical management
The course of sickle cell disease varies widely with many persons being asymptomatic.   In the early days sicklers with low haemoglobin levels were subject to repeated transfusions, which overloaded their body with iron and resulted in early deaths.  This gave rise to the myth that persons with sickle cell disease always died young.  This is not true. 

Sicklers are susceptible to streptococcus infection and mortality from this cause has been dramatically reduced by monthly antibiotic injections.  Parents are taught how to detect enlargement of the spleen at home and are instructed to bring these children into hospital when splenic enlargement is detected.  These two measures along with cessation of over transfusions have dramatically changed the prognosis of the disease.  

Sicklers can be expected to live relatively trouble free lives.  I remember one individual at KC in my time who had frequent painful crises.  My brother Barry would spend hours at his home playing music for him, as this was his main form of relief.  The fact that persons with a sickle disorder / sicklers could live long and healthy lives was dramatically brought to the medical worlds attention by the University of the West Indies sickle cell unit when they found people with SS disorder, with normal life expectancy living in Lawrence Tavern in rural Jamaica.

Recently a sickler has been cured of the disorder by bone marrow transplantation, but this is not a widely accepted method of treatment as the risks of that procedure may not be worth the potential benefits.  The Sickle Cell research Unit at the University of The West Indies Mona remains a world leading research centre for the study of the disease and has resulted in dramatic improvements and management of the condition.

Editor’s Note:  Dr. Hugh Vaughan CD, MBBS (UWI), FRCSEd, FRCOphth entered KC in January, 1959 and left in 1966.  He was not a sportsman but debated for KC in several competitions, participated in Schools Drama Festival, and acted in Lelawalah, the Maid of Niagara, a production of the KC - St Hugh’s Operatic Society. One of the highlights and most treasured times of his life was serving as  Headboy in 1965-66.