Thalassemia Jon Clapp ISAT 351 Presentation 12 April 1999

A Couple of Questions u What is one of the most common diseases in today’s society? u To be more explicit, what is one of the most common genetically inherited diseases?

The Classification of Thalassemia u Thalassemia is a form of anemia. u An anemia is a disease that has had its genetic code mutated (altered) and cannot transcribe and translate the correct protein for use in the red blood cells. u Examples of anemia: QSickle cell. QIron-deficient. QThe Thalassemias.

Definition of Thalassemia u Dr. Quirolo of the Children’s Hospital of Oakland states, “The thalassemias are a diverse group of genetic blood diseases characterized by absent or decreased production of normal hemoglobin, resulting in microcytic anemia of varying degree.” u Mycrocytic anemia is a general form of anemia that refers to a decrease in the size of the red blood cells.

Two Major Forms of Thalassemia u Alpha RCaused by a decrease in production of the alpha-globin genes due to a deletion of mutation of one or more of four alpha-globin genes on chromosome 16. u Beta RCaused by mutations of the beta-globin genes on chromosome 11.

Five Types of Alpha Thalassemia u Silent Carrier - 3 functional genes. u Alpha Thalassemia Trait - 2 functional & 2 non-functional genes. u Hemoglobin H disease - 1 functional gene. u Hemoglobin H-Constant Spring - 1 functional gene and 1 gene that is cut short by termination in transcription. u Alpha Thalassemia Major - no functional genes.

Three Types of Beta Thalassemia u Beta Thalassemia Trait - one affected allele of chromosome 11. u Beta Thalassemia Intermedia - one or two affected alleles, but only mild syptoms experienced. u Beta Thalassemia Major - both alleles are affected and require blood transfusions and drug treatments to survive.

History of Thalassemia u Beta Thalassemia was first described by Thomas Cooley, known as Cooley’s anemia in RSymptoms exhibited: u Anemia u Splenomegaly (enlargement of the spleen due to increased activity/filtering of the red blood cells) u Enlargement of the Liver u Discoloration of the Skin u Enlargement of the Cranial and Facial Bones

History of Thalassemia (cont.) u About the same time as Cooley, a group of Italians described the Thalassemia Trait. u It was not realized until 1940 that the two were related. u Alpha Thalassemia was first recognized in 1955 by groups in the United States and Greece. u The thalassemias seemed to be more prevalent in the the Mediterranean area.

Mutations of the Beta-Globin Gene

Example of a Frameshift Mutation

Differences Between Thalassemia and Iron-deficient Anemia u Thalassemia is hereditary. u Iron is present in the bone marrow. u Microcytosis is usually very severe. u Basophilic stippling of red blood cells is common. u Does not respond to Iron therapy. u Iron-deficient anemia is not hereditary. u Iron is absent in the bone marrow. u Microcytosis is mild or absent. u Less frequent basophilic stippling of red blood cells. u Responds to iron therapy.

Similarities Between Thalassemia and Iron-Deficient Anemia u Red Blood Cell fragility is decreased. u Plasma iron may be decreased. u Target cells are present.

Genotype Analysis of Thalassemia

Thalassemia and Malaria u In 1949, J.B.S. Haldane proposed the “Malaria Hypothesis,” which states that “the corpuscles of the anemic heterozygote are smaller than normal, and more resistant to hypotonic solutions. It is at least conceivable that they are also more resistant to attacks by the sporozoa which cause malaria.” u Studies have shown that individuals born with the thalassemia trait can survive malaria and pass the trait onto the next generation, but it is not known how individuals with thalassemia are protected from malaria.

Personal Pedigree Chart for Beta Thalassemia Minor ? Non-infected Male Infected Male Non-infected Female Infected Female Frances TalbotGrady Sahms Robert Sahms Patricia SahmsSylvia SahmsPaul Blackwell Ryan ClappJon ClappStephen Clapp Daryl ClappPaul BlackwellDiane Blackwell

Recent Symptoms Experienced u During a soccer game: RSudden shortness of breath. RHeart rate higher than normal exercise rate. RWeakness throughout entire body. RStomach knotting and nausea. RExtreme pain and lightheadedness to the point of fainting.

Cures, Treatment, and Research u There is no cure for thalassemia. u The current treatments are blood transfusions and bone marrow transplants, but rejections and overload of elements has been a problem (especially iron). u Possible investigations into the area of gene therapy, but nothing has been announced about the progress or validity.