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.
Since thalassemia is an inherited genetic disorder, symptoms may present early. In the most severe forms, symptoms manifest shortly after birth while with other forms, symptoms may not present until later (by age two).
Persons with mild forms of thalassemia may be asymptomatic and not experience any symptoms at all or may experience mild anemia which is mistaken for iron deficiency anemia.
- Shortness of breath;
- Pale appearance;
- Yellow discoloration of skin (jaundice);
- Facial bone deformities;
- Slow growth;
- Protruding abdomen; and
- Dark urine.
In addition, thalassemia can cause other health problems such as delayed puberty and slow growth rate, bone problems (including osteoporosis, brittle or deformed bones –- particularly in the facial area), enlarged spleen, severe anemia, heart disease, and liver problems.
What is the genetic pattern of inheritance of beta thalassemia?
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.
Often referred to as “Mediterranean Anemia,” thalassemias tend to affect persons of Mediterranean descent. Persons of Italian, Filipino, Indian Asian, South Asian, African, Greek, Middle Eastern and Chinese descent are also at greater risk for developing thalassemia.
In addition to ethnicity, persons with a family history of thalassemia are at greater risk for developing the disorder.
The hemoglobin genes are defective in persons with thalassemia. The defective gene results in lower red blood cell and hemoglobin count than normal.
In addition, the existing red blood cells are destroyed at a much higher rate than what occurs in the normal red blood cell life cycle.
Hemoglobin is comprised of two separate protein chains: alpha and beta.
Depending upon which gene is defective, persons may develop either alpha-thalassemia or beta-thalassemia.
A person develops alpha-thalassemia if they inherit at least one defective alpha hemoglobin gene from either parent.
According to the National Heart Lung and Blood Institute, persons of “Southeast Asian, Indian, Chinese or Filipino origin or ancestry” are more prone to develop alpha-thalassemia.
The alpha hemoglobin chain consists of four genes (two obtained from each parent) so it is possible to inherit four defective alpha genes in all.
The more defective alpha hemoglobin genes which you inherit, the more severe the form of the disease.
- Alpha-thalassemia silent carrier (one defective gene): Disease carrier. No symptoms;
- Alpha-thalassemia minor or alpha-thalassemia trait (two defective genes): Very mild symptoms;
- Hemoglobin H disease (three defective genes): Moderate to severe symptoms; and
- Alpha-thalassemia major or hydrops fetalis (four defective genes): Generally fatal and causes death shortly after birth.
Beta-thalassemia occurs when at least one of the two inherited beta hemoglobin genes are defective. This form of thalassemia occurs most often in persons of “Mediterranean (Greek, Italian, and Middle Eastern), Asian, or African origin or ancestry.” (NHLBI).
The severity of this form of thalassemia depends upon whether one or two defective genes have been inherited.
- Beta-thalassemia minor or beta-thalassemia trait (one defective gene): Mild symptoms; and
- Beta-thalassemia major (also known as Cooley’s anemia): Symptoms present by age two.
The diagnosis of thalassemia major and minor
Persons with thalassemias have smaller sized red blood cells than unaffected people as well as low red blood cell counts (anemia).
Thalassemia major and thalassemia minor can now be diagnosed (and distinguished from one another) not only by conventional clinical and blood testing, but also by molecular tests.
These tests permit accurate diagnosis to be made at any time, even before birth (in fact, well before the beta chains are even synthesized).
Since the disorder is inherited, there is no cure for thalassemia.
However, a number of treatments are available depending on the form and severity of the disorder including: blood transfusions, supplements (iron and folic acid) and iron chelation therapy (Deferoxamine, Deferasirox).
In some instances, persons may be treated by a transplant of the blood and bone marrow stem cells. The percentage of people who receive transplants is relatively small since it is difficult to find suitable donors.