Thalassemia, also known as Mediterranean anemia, Cooley’s anemia (named after Dr. Thomas Cooley), or erythroblastic anemia, is a hereditary group of hemolytic anemias characterized by defective synthesis in the polypeptide chains necessary for hemoglobin production. Consequently, red blood cell (RBC) synthesis is also impaired. Thalassemia is closely related to the sickle cell trait, but infrequently seen in blacks.
The word thalassemia comes from the Greek thalassa, meaning ‘sea’ (because it was observed originally in persons around the Mediterranean) + -emia, a suffix meaning a ‘condition of the blood’.
The two most common forms are Alpha-thalassemia and Beta-thalassemia, but there is also a delta form and one that combines both delta and beta chains of hemoglobin. The delta form is usually symptom free. The combined form clinically resembles thalassemia minor.
Alpha-thalassemia is caused by diminished synthesis of alpha chains of hemoglobin. It is seen most often in Chinese, Thai, African, and Mediterranean peoples. Over forty mutations have been identified that cause alpha-thalassemia.
Beta-thalassemia is caused by diminished synthesis of beta chains of hemoglobin. It is seen most often in those people whose ancestry came from the Mediterranean basin (Italy, Sicily, Sardinia, Greece, Crete, Cyprus, Syria, or Turkey). Thus far, over 140 specific conditions have been found to cause beta-thalassemia, which is the most common form of this disorder, occurring in three distinct types: thalassemia major, thalassemia intermedia, and thalassemia minor.
In all these disorders, total or partial deficiency of beta polypeptide chain production impairs hemoglobin synthesis and results in continual production of fetal hemoglobin, lasting past the neonatal period.
Thalassemia major and thalassemia intermedia result from homozygous inheritance of the partially dominant autosomal gene responsible for this trait.
Thalassemia minor results from heterozygous interitance of the same gene. The severity of the resulting anemia depends on whether the patient is homozygous or heterozygous for the thalassemic trait. Homozygous forms are manifested by profound anemia or death in utero, and heterozygous forms by erythrocyte anomalies ranging from mild to severe. Heterozygous refers to the presence of two genes at the same loci on different chromosomes that relate to the same characteristic. The two genes in this case are different – one is recessive, the other dominant. Homozygous refers to two genes at the same loci on different chromosomes relating to the same characteristic. The two genes in this case are identical – both recessive or both dominant.
Prognosis for B-thalassemia varies. Those with thalassemia major seldom survive to adulthood but children with the intermedia form develop normally into adulthood although puberty is usually delayed. Patients with thalassemia minor can expect a normal life span.
Initial signs are as follows:
- Thalassemia major: pallor, yellow skin, and sclera in infants ages three to six months. Later, signs include severe anemia; splenogmegaly or hepatomegaly, with abdominal enlargement; frequent infections; leg ulcers; bleeding tendencies (especially toward epistaxis); anorexia; altered appearance with small body, large head, and possible mongoloid features and mental retardation. Those who have mongoloid features do so because bone marrow hyperactivity has thickened the bone at the base of the nose. As these children grow older, they become susceptible to pathologic fractures, as a result of expansion of the marrow cavities with thinning of the long bones. They are also subject to cardiac arrhythmias, heart failure, and other complications that result from iron deposits in the heart and in other tissues from repeated blood transfusions.
- Thalassemia intermedia: signs and symptoms of anemia, jaundice, splenomegaly, and possible signs of hemosiderosis (because of increased iron stores in tissues)
- Thalassemia minor: mild anemia but usually producing no symptoms and being often overlooked
Treatment of thalassemia major is essentially supportive, but none is generally required for the intermedia or minor forms. Blood transfusions provide temporary relief, but eventually there is a toxic accumulation of iron caused by the increased breakdown of red cells. Iron supplements are contraindicated in all forms of thalassemia.
Diagnostic tests: (See separately.)