Beta-thalassemia is one of a group of hereditary blood conditions that result from reduced or absent synthesis of the beta-globin chain of the hemoglobin molecule. It occurs as the result of a point mutation or less commonly, a deletion in the gene that codes for the beta chain, on chromosome 11. It occurs in 1 of 10,000-100,000 people, depending on the ethnicity. It is inherited in an autosomal recessive manner. The symptoms vary from none to severe anemia.
Three main forms are clinically distinguished, namely, beta-thalassemia major, beta-thalassemia intermediate, and beta-thalassemia minor, depending on the time of presentation of anemia, and its severity. These forms depend upon the type of inheritance, namely homozygous or heterozygous. Beta-thalassemia may also occur in combination with other hemoglobin defects.
Thalassemia major presents early in life with anemia severe enough to warrant regular blood transfusions. Other symptoms include:
- poor growth
- enlargement of the liver and spleen due to the breakdown of red cells containing the abnormal hemoglobin
- leg ulcers
- bone changes secondary to marrow expansion
- the appearance of other masses due to the formation of blood outside the bone marrow.
As a result of repeated transfusions to keep the hemoglobin level between 9 and 10.5 g/dL, iron overload occurs. The excessive iron levels lead to iron toxicity, reflected as:
- growth failure
- sexual immaturity
- diabetes mellitus
- hypofunctioning of several endocrine glands
- heart failure due to cardiac muscle weakening
- liver cirrhosis following fibrosis.
Cardiac complications due to hemosiderosis are the most common cause of death.
Other secondary complications include the possibility of infection with hepatitis B and C viruses, and HIV infection.
The intermediate forms of thalassemia show the same type of symptoms but at a later age, and with less severity. More distinctive symptoms of this form include thrombosis of the deep veins, presenting as:
- leg thrombosis
- portal vein thrombosis
- stroke or
These are more common in the intermediate form as compared to the major form. Diabetes, hypogonadism and thyroid insufficiency are less common, however.
Thalassemia minor is often asymptomatic, but sometimes patients have mild to moderate anemia.
Diagnosis and treatment
Diagnosis is based on the presence of characteristic findings on hematologic testing. Thus the RBC indices show a microcytic hypochromic anemia. Peripheral blood smear examination shows the presence of nucleated red cells, as a result of accelerated but ineffective hemopoiesis. Hemoglobin analysis by electrophoresis and other means shows the type and quantity of abnormal hemoglobin being produced.
The diagnosis of thalassemia is confirmed by molecular genetic testing. Genetic counseling is advisable because of the mode of inheritance.
Treatment includes regular transfusions of packed red cells, prevention of iron overload by iron chelating agents, and early treatment of complications related to iron accumulation. When there is severe hemolysis which makes it difficult to maintain a normal hemoglobin level, and precipitates secondary complications such as thrombosis and splenic sequestration, splenectomy is often helpful. Definitive management is by bone marrow transplantation.