Sickle

Cell Anemia

We feel that this report looks a lot better single-spaced. A Brief History of

Sickle Cell Disease Sickle Cell Disease in African Tradition Sickle cell disease
has been known to the peoples of Africa for hundreds, and perhaps thousands, of
years. In West Africa various ethnic groups gave the condition different names:

Ga tribe: Chwechweechwe Faute tribe: Nwiiwii Ewe tribe: Nuidudui Twi tribe:

Ahotutuo Sickle Cell Disease in the Western Literature Description of Sickle

Cell Disease In the western literature, the first description of sickle cell
disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a
patient of his from the West Indies had an anemia characterized by unusual red
cells that were "sickle shaped". Relationship of Red Cell Sickling to

Oxygen In 1927, Hahn and Gillespie showed that sickling of the red cells was
related to low oxygen. Deoxygenation and Hemoglobin In 1940, Sherman (a medical
student at Johns Hopkins) noted a birefringence of deoxygenated red cells,
suggesting that low oxygen altered the structure of the hemoglobin in the
molecule. Protective Role of Fetal Hemoglobin in Sickle Cell Disease Janet

Watson, a pediatric hematolist in New York, suggested in 1948 that the paucity
of sickle cells in the peripheral blood of newborns was due to the presence of
fetal hemoglobin in the red cells, which consequently did not have the abnormal
sickle hemoglobin seen in adults. Abnormal Hemoglobin in Sickle Cell Disease

Using the new technique of protein electrophoresis, Linus Pauling and colleagues
showed in 1949 that the hemoglobin from patients with sickle cell disease is
different than that of normals. This made sickle cell disease the first disorder
in which an abnormality in a protein was known to be at fault. Amino Acid

Substitution in Sickle Hemoglobin In 1956, Vernon Ingram, then at the MRC in

England, and J.A. Hunt sequenced sickle hemoglobin and showed that a glutamic
acid at position 6 was replaced by a valine in sickle cell disease. Using the
known information about amino acids and the codons that coded for them, he was
able to predict the mutation in sickle cell disease. This made sickle cell
disease the first known genetic disorder. Preventive Treatment for Sickle Cell

Disease Hydroxyurea became the first (and only) drug proven to prevent
complications of sickle cell disease in the Multicenter Study of Hydroxyurea in

Sickle Cell Anemia, which was completed in 1995. How Does Sickle Cell Cause

Disease? The Mutation in Hemoglobin Sickle cell disease is a blood condition
primarily affecting people of African ancestry. The disorder is caused by a
single change in the amino acid building blocks of the oxygen-transport protein,
hemoglobin. This protein, which is the component that makes red cells
"red", has two subunits. The alpha subunit is normal in people with
sickle cell disease. The -subunit has the amino acid valine at position 6
instead of the glutamic acid that is there normally. The alteration is the basis
of all the problems that occur in people with sickle cell disease. The schematic
diagram shows the first eight-of the 146 amino acids in the -globin subunit of
the hemoglobin molecule. The amino acids of the hemoglobin protein are
represented as a series of linked, colored boxes. The lavender box represents
the normal glutamic acid at position 6. The dark green box represents the valine
in sickle cell hemoglobin. The other amino acids in sickle and normal hemoglobin
are identical. The molecule, DNA (deoxyribonucleic acid), is the fundamental
genetic material that determines the arrangement of the amino acid building
blocks in all proteins. Segments of DNA that code for particular proteins are
called genes. The gene that controls the production of the -subunit of
hemoglobin is located on one of the 46 human chromosomes (chromosome #11).

People have twenty-two identical chromosome pairs (the twenty-third pair is the
unlike X and Y-chromosomes that determine a person\'s sex). One of each pair is
inherited from the father, and one from the mother. Occasionally, a gene is
altered in the exchange between parent and offspring. This event, called
mutation, occurs extremely infrequently. Therefore, the inheritance of sickle
cell disease depends totally on the genes of the parents. If only one of the -globin
genes is the "sickle" gene and the other is normal, the person is a
carrier. The condition is called sickle cell trait. With a few rare exceptions,
people with sickle cell trait are completely normal. If both -globin genes
code for the sickle protein, the person has sickle cell disease. Sickle cell
disease is determined at conception, when a person acquires his/her genes from
the parents. Sickle cell disease cannot be caught, acquired,