Diseases

The thalassemias are a group of genetic (inherited) blood disorders that share in common one feature, the defective production of hemoglobin, the protein that enables red blood cells to carry and deliver oxygen. There are many different mechanisms of defective hemoglobin synthesis and, hence, many types of thalassemia.

The most familiar type of thalassemia is beta thalassemia. It involves decreased production of normal adult hemoglobin (Hb A), the predominant type of hemoglobin from soon after birth until death. (All hemoglobin consists of two parts: heme and globin). The globin part of Hb A has 4 protein sections called polypeptide chains. Two of these chains are identical and are designated the alpha chains. The other two chains are also identical to one another but differ from the alpha chains and are termed the beta chains. In persons with beta thalassemia, there is reduced or absent production of beta globin chains.

The gene for beta thalassemia is not evenly distributed among peoples. It is, for example, relatively more frequent in people of Italian and Greek origin, both of which are peoples from the Mediterranean. Because of this, thalassemia major has been called Mediterranean anemia. The name thalassemia was coined at the University of Rochester in upstate New York by the Nobel Prize-winning pathologist George Whipple and the professor of pediatrics William Bradford from the Greek thalassa for sea and -emia, meaning the blood. Thalassemia means "sea in the blood." But for the Greeks, the sea was the Mediterranean, so thalassemia also conveys the idea of the Mediterranean in the blood. The reason that the gene for beta thalassemia is relatively common, for example, among people of Italian and Greek origin is that parts of Italy and Greece were once full of malaria. The presence of thalassemia minor (like sickle cell trait in Africa) afforded protection against malaria, and therefore, this gene thrived.

There are two forms of beta thalassemia. They are thalassemia minor and thalassemia major (which is also called Cooley's anemia).Thalassemia minor: The individual with thalassemia minor has only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be heterozygous for beta thalassemia.Persons with thalassemia minor have (at most) mild anemia (slight lowering of the hemoglobin level in the blood). This situation can very closely resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have a normal blood iron level (unless they are iron deficient for other reasons). No treatment is necessary for thalassemia minor. In particular, iron is neither necessary nor advised.Thalassemia major (Cooley's anemia): The child born with thalassemia major has two genes for beta thalassemia and no normal beta-chain gene. The child is homozygous for beta thalassemia. This causes a striking deficiency in beta chain production and in the production of Hb A. Thalassemia major is a significant illness.The clinical picture associated with thalassemia major was first described in 1925 by the American pediatrician Thomas Cooley. Hence, the name Cooley's anemia in his honor.At birth the baby with thalassemia major seems entirely normal. This is because the predominant hemoglobin at birth is still fetal hemoglobin (HbF). HbF has two alpha chains (like Hb A) and two gamma chains (unlike Hb A). It has no beta chains so the baby is protected at birth from the effects of thalassemia major.Anemia begins to develop within the first months after birth. It becomes progressively more and more severe. The infant fails to thrive (to grow normally) and often has problems feeding (due to easy fatigue from lack of oxygen due to the profound anemia), bouts of fever, diarrhea, and other intestinal problems.

The pattern of genetic transmission of beta thalassemia (and sickle cell disease) was deciphered by James V. Neel when he was at the University of Rochester (and later at the University of Michigan). Dr. Neel recognized that the parents of children with thalassemia major had thalassemia minor with one beta thalassemia gene. When these parents had children, they have a 25% chance of having a thalassemia major child (with both genes for beta thalassemia), a 50% chance of having children with thalassemia minor (with only one gene for beta thalassemia), and a 25% chance of having a child without thalassemia major or minor (with both genes for normal beta chains). This form of inheritance is medically referred to as an autosomal recessive pattern.