Hemoglobinopathies are genetic (inherited) disorders of hemoglobin, the oxygen-carrying protein of the red blood cells.
The hemoglobin molecule is composed of four separate polypeptide chains of amino acids, two alpha chains and two beta chains, as well as four iron-bearing heme groups that bind oxygen. The alpha chains are coded for by two similar genes on chromosome 16; the beta chains by a single gene on chromosome 11. Mutations and deletions in these genes cause one of the many hemoglobinopathies.
In general, hemoglobinopathies are divided into those in which the gene abnormality results in a qualitative change in the hemoglobin molecule and those in which the change is quantitative. Sickle cell anemia (sickle cell disease) is the prime example of the former, and the group of disorders known as the thalassemias constitute the latter. It has been estimated that one third of a million people worldwide are seriously affected by one of these genetic disorders.( Weatherall, 2001 705)
Sickle cell anemia (SSA), an autosomal recessive disorder more common in the Black population, is caused by a single mutation in the gene that codes for the beta polypeptide. Approximately 1/400 to 1/600 African-Americans are born with the disorder, and, one in ten is a carrier of one copy of the mutation. In certain parts of the African continent, the prevalence of the disease reaches one in fifty individuals.( Weatherall, 2001 709)
The sickle cell mutation results in the substitution of the amino acid valine for glutamic acid in the sixth position of the beta polypeptide. In turn, this alters the conformation of the hemoglobin molecule and causes the red blood cells to assume a characteristic sickle shape under certain conditions. These sickle-shaped cells, no longer able to pass smoothly through small capillaries, can block the flow of blood. This obstruction results in symptoms including growth retardation, severe pain crises, tissue and organ damage, splenomegaly, and strokes. Individuals with SSA are anemic and prone to infections, particularly pneumonia, a significant cause of death in this group. Some or all of these symptoms are found in individuals who have the sickle mutation in both copies of their beta-globin gene. Persons with one abnormal gene and one normal gene are said to be carriers of the sickle cell trait. Carriers are unaffected because of the remaining normal copy of the gene.
The thalassemias are a diverse group of disorders characterized by the fact that the causative mutations result in a decrease in the amount of normal hemoglobin. Thalassemias are common in Mediterranean populations as well as in Africa, India, the Mideast, and Southeast Asia. The two main types of thalassemias are alpha-thalassemia due to mutations in the alpha polypeptide and beta-thalassemia resulting from beta chain mutations.
Since individuals possess a total of four genes for the alpha polypeptide (two genes on each of their two chromosomes 16), disease severity depends on how many of the four genes are abnormal. A defect in one or two of the genes has no clinical ...