Beta Thalassemia

views updated

Beta thalassemia


Beta thalassemia is an inherited disorder that affects the beta globin (protein molecules) chains. These chains are required for the synthesis of hemoglobin A (a compound in the blood that carries oxygen to the cells and carbon dioxide away from the cells). A decrease of beta globin chains causes early destruction of the red blood cells. There are four types of the disorder and they range in severity of symptoms.

The thalassemias were first discovered by Thomas Cooley and Pearl Lee in 1975. Early cases of the disease were reported in children of Mediterranean descent and therefore the disease was named after the Greek word for sea, thalasa.


Beta thalassemia results due to a defect in the beta globin gene . Shortly after birth, the body converts from producing gamma globin chains, which pair with alpha globin chains to produce fetal hemoglobin (HbF), to producing beta globin chains. Beta globin chains pair with alpha globin chains to produce adult hemoglobin (HbA). Due to the decreased amount of beta globin chains in individuals with beta thalassemia, there is an excess of free alpha globin chains. The free alpha globin chains become abnormal components in maturing red blood cells. This leads to destruction of the red blood cells by the spleen and a decreased number of red blood cells in the body. Individuals with beta thalassemia may continue producing gamma globin chains in an effort to increase the amount of HbF and compensate for the deficiency of HbA.

There are four types of beta thalassemias. These include beta thalassemia minima, minor, intermedia, and major. Beta thalassemia minima and beta thalassemia minor are less severe and usually asymptomatic. Beta thalassemia minima is known as the silent form of the disorder. There are no major hematologic (blood and blood forming tissue) abnormalities. The only noted abnormality is the decrease in beta globin production. Beta thalassemia minor is rare. A person with this type of the disorder inherits only one beta globin gene. Although children are usually asymptomatic, they do have abnormal hematologic (blood) findings.

Beta thalassemia intermedia and major often require medical treatment. Beta thalassemia intermedia is usually found during the toddler or preschool years. It is considered to be the mild form of thalassemia major and frequently does not require blood transfusions. Thalassemia major is typically diagnosed during the first year of life. There are two designations for beta thalassemia major, beta zero and beta positive. In type beta zero there is no adult hemoglobin (HbA) present due to the very small production of beta globin. In type beta positive there is a small amount of HbA detectable. In both forms of beta thalassemia major, individuals will experience severe fatigue due to the decrease or absence of adult hemoglobin (HbA), which is needed to carry oxygen to the cells, and is necessary for cellular survival.

Alternate names associated with beta thalassemia minor include thalassemia minor, minor hereditary leptocyosis, and heterozygous beta thalassemia. Alternate names associated with beta thalassemia intermedia include intermedia Cooley's anemia and thalassemia intermedia. Alternate names associated with beta thalassemia major include Cooley's anemia, erythroblastoic anemia of childhood hemoglobin lepore syndrome, major hereditary leptocytosis, Mediterranean anemia, mocrocythemia, target cell anemia, and thalassemia major.

Genetic profile

Beta thalassemia is an autosomal recessive disorder. A person who is a carrier will not develop the disorder but may pass the gene for the disorder onto their child. There is a 25% chance for each pregnancy that the disorder will be passed onto the children if both parents are carriers for the trait and a 100% chance if both parents have the trait.

Individuals with thalassemia minor are carriers for the beta globin gene and therefore possess only one of the genes necessary to express the disorder. These individuals are usually asymptomatic or have very few symptoms. Individuals with thalassemia major express both abnormal genes for beta globin and therefore will have the disease. These individuals show severe symptoms for the disorder.

The beta globin gene is found on chromosome 11. Mutations (inappropriate sequence of nucleotides, the building blocks of genes) resulting in beta thalassemia are usually caused by substitutions (switching one nucleotide for another) although some may be caused by deletions (part of a chromosome, a structure that places genes in order, is missing). Substitutions occur within the nucleotide and deletions occur on the chromosome that the beta globin gene is found on.


Beta thalassemia affects males and females equally. It commonly occurs in people of Mediterranean heritage. It is also found in families descending from Africa, the Middle East, India, and Southeastern Asia.

Signs and symptoms

Symptoms for beta thalassemia vary in severity based on the type of the disorder.

Beta thalassemia minima

There are no symptoms for this type. It is considered to be a "silent" form of beta thalassemia.

Beta thalassemia minor

Individuals with this type of beta thalassemia may be asymptomatic or experience very few symptoms. Symptoms may be worse in individuals that are pregnant, under stress, or malnourished. Symptoms may include:

  • Fatigue. This may be the only symptom that an individual with beta thalassemia minor exhibits. Fatigue is caused by the decreased oxygen carrying capacity of the red blood cells, resulting in lowered oxygenation for cells and tissues.
  • Anemia. Anemia is a decrease in the amount of hemoglobin in the blood. Hemoglobin is needed to carry oxygen on the red blood cells. In beta thalassemia minor there is a decrease in adult hemoglobin (HbA) and an increase in hemoglobin A2. Hemoglobin A2 is a minor hemoglobin that contains delta globin chains in the place of beta globin chains. Anemia is most likely to occur during pregnancy.
  • Splenomegaly. Enlargement of the spleen may occur due to increased removal of defective red blood cells. This is rarely seen in individuals with beta thalassemia minor and may be accompanied by pain in the upper left portion of the abdomen.
  • Skin. The skin color of individuals with beta thalassemia minor may be pale (pallor) due to oxygen deprivation in blood.

Beta thalassemia intermedia

Individuals with this form of beta thalassemia usually begin to show symptoms during toddler or preschool years. These individuals present with many of the same symptoms as beta thalassemia major, however, symptoms for beta thalassemia intermedia are less severe and may include:

  • Anemia. In individuals with beta thalssemia intermedia, hemoglobin levels are greater than 7g/dl but they are less than normal. Normal levels for hemoglobin are 13-18 for males and 12-16 for females.
  • Hyperbilirubinemia. Bilirubin is a yellow pigment of bile that is formed by the breakdown of hemoglobin in the red blood cells. Excess amounts of bilirubin in the blood is caused by the increased destruction of red blood cells (hemolysis) by the spleen.
  • Splenomegaly. Enlargement of the spleen is caused by increased removal of defective red blood cells. Red blood cells are defective due to the increased amount of inclusion bodies caused by circulation of free alpha globin chains.
  • Hepatomegaly. Enlargement of the liver may be caused by a build-up of bile due to increased amounts of bilirubin in the blood.
  • Additional abnormalities. Individuals with beta thalassemia intermedia may have a yellow discoloration (jaundice) of the skin, eyes, and mucous membranes caused by increased amounts of bilirubin in the blood. Individuals may also suffer from delayed growth and abnormal facial appearance.

Beta thalassemia major

Individuals with this form of beta thalassemia present with symptoms during the first year after birth. Symptoms are severe and may include:

  • Severe anemia. Individuals with beta thalassemia major suffer from a hemoglobin level of less than 7 mg/dl.
  • Hyperbilirubinemia. Individuals will have an increased amount of bilirubin in the blood. This is due to the increased destruction of red blood cells (hemolysis) by the spleen.
  • Jaundice. Individuals may experience a yellow discoloration of the skin, eyes, and mucous membranes caused by increased amounts of bilirubin in the blood.
  • Extramedullary hematopoiesis. Abnormal formation of red blood cells outside of the bone marrow may occur in the body's attempt to compensate for decreased production of mature red blood cells. This can cause masses or the enlargement of organs, which may be felt during physical examination.
  • Splenomegaly. Enlargement of the spleen may result due to increased destruction of red blood cells and the occurrence of extramedullary hematopoiesis.
  • Hepatomegaly. Enlargement of the liver may result due to accumulation of bile or the occurrence of extra-medullary hematopoiesis.
  • Cholithiasis. This is the presence of stones in the gallbladder, which may lead to blockage and cause bile to be pushed back into the liver.
  • Bone marrow expansion. The bone marrow becomes expanded due to the increase of the production of red blood cells (erythropoiesis) in an attempt to produce more mature red blood cells and decrease the anemic state of the body.
  • Facial changes. Due to expansion of the bone marrow, children will develop prominent cheekbones, depression of the nasal bridge, and protrusion of the upper jaw. These facial changes are a classic sign in children with untreated beta thalassemia.
  • Iron overload. Iron overload of the tissues can be fatal and is due to erythroid (red blood cell) expansion. The increased destruction of a vast amount of red blood cells causes increased amounts of iron to be released from the hemoglobin.
  • Cardiovascular abnormalities. Accumulation of iron deposits in the heart muscle can lead to cardiac abnormalities and possibly cardiac failure.
  • Additional abnormalities. Individuals may also suffer from pale skin, fatigue, poor feeding, failure to thrive, and decreased growth and development.


Completing a family history, performing a complete physical examination, and results of blood (hematological) tests can lead to a diagnosis of beta thalassemia. Bone abnormalities and masses or enlarged organs may be recognized during physical examination. Prenatal testing to detect beta thalassemia can be done by completing an amniocentesis (obtaining a sample of amniotic fluid, which surrounds the fetus during pregnancy). Lab results will vary depending on the type of beta thalassemia that an individual presents with.

Normal hemoglobin results are 13-18 g/dL for males and 12-16 g/dL for women. Normal red blood cell counts are 4.7-6.1 million for males and 4.2-5.4 million for females. In individuals with beta zero form of beta thalassemia major, there will be no HbA present in the blood.

Symptoms of beta thalassemia minor may be similar to those of sideroblastic anemia (a disorder characterized by low levels of hemoglobin, fatigue, and weakness) and sickle cell disease (a disease that changes red blood cell shape, rendering it incapable of functioning).

Symptoms of beta thalassemia major may be similar to those of hereditary spheocytic hemolytic anemia (presence of sphere shaped red blood cells).

Treatment and management

Beta thalassemia minima and minor usually require no treatment. Pregnant women that suffer from beta thalassemia minor may require blood transfusions to keep hemoglobin levels normal. Individuals with beta thalassemia intermedia and major can be treated with blood transfusions and iron chelation (binding and isolation of metal) therapy. Although individuals with beta thalassemia intermedia do not usually require transfusions, in certain cases it may be necessary.

Blood transfusions are performed in individuals that present with severe symptoms such as anemia and impaired growth and development. Children may receive transfusions every four to six weeks. A high risk associated with transfusions is iron overload, which is fatal. Iron overload results from inadequate amounts of serum transferring (a molecule that exchanges iron between body tissues), which is needed to bind and detoxify iron. Iron accumulation can lead to dysfunction of the heart, liver, and endocrine glands.

Monitoring iron levels in the body is essential. Individuals receiving blood transfusions should keep total body iron levels at 3-7 mg of iron per gram of body weight. There are three methods of measuring iron levels in the body. These include a serum ferritin test, liver biopsy, and radiological study performed by the Superconducting Quantum Interference Device (SQUID).

The serum ferritin (iron storage protein) test is completed by testing a blood sample for ferritin content. This method is the easiest and most affordable way of testing for body content of iron, but it is not reliable. A liver biopsy is an invasive procedure that requires removal of a small piece of the liver. Studies have shown that a liver biopsy is very accurate in measuring the level of iron stores in the body. The third method, which requires a Superconducting Quantum Interference Device, is also very accurate in measuring iron stores. The SQUID is a highly specialized machine and few centers in the world possess this advanced technology.

Iron overload can be prevented with the use of iron chelating therapy. Chelating agents attract the excess iron and assist with the process of binding and detoxifying this iron in the body. The drug deferoxamine (desferol) is one of the most widely used iron chelating agents. Treatment is completed through nightly infusions of deferoxamine by a pump or with daily intramuscular injections. Infusion by pump is used for the administration of high doses and low doses are given through injections. Iron chelation therapy by oral administration with a drug named deferiprone has been under experimental study and may be an alternative to deferoxamine.

Individuals receiving blood transfusions should pay close attention to iron intake in the diet. It is recommended that children under age 10 keep dietary iron intake at 10 mg/day or less. Individuals age 11 or older should keep dietary iron intake at 18 mg/day or less. Foods high in iron include: beef, beans, liver, pork, peanut butter, infant cereal, cream of wheat, prunes, spinach, raisins, and leafy green vegetables. Individuals should read food labels and avoid using cast iron cookware, which can provide more iron in food during cooking.

Increased amounts of iron in the body can cause a decrease in calcium levels, which impairs organs that aid in building strong bones. Individuals with beta thalassemia major are at risk for developing osteoporosis (disease resulting in weakened bones). Increased dietary intake of calcium and vitamin D can help increase the storage of calcium in the bones, thus making the bones stronger and decreasing the risk for osteoporosis.

Bone marrow transplantation is another form of treatment for beta thalassemia. Outcomes of transplantation are greatly influenced by the health of the individual. This form of treatment is only possible if the individual has a suitable donor.

Researchers are investigating the use of the drugs hydroxyurea and butyrate compounds to increase the amounts of fetal and total hemoglobin in individuals with beta thalassemia. Studies using gene therapy , such a stem cell replacement, are also being conducted.

Social and lifestyle issues Children with beta thalassemia major that is not diagnosed and treated early may develop changes in the bone structure of the face due to the expansion of bone marrow. Supportive counseling may benefit children who feel inadequate or refuse to participate in social activities due to their appearance.

Adolescents may require counseling concerning the effects that blood transfusions and iron chelation therapy may have on their social lifestyle.

Parents may need to seek counseling or attend support groups that focus on the time demand and lifestyle changes of caring for a child diagnosed with beta thalassemia.


Prognosis for beta thalassemia is good for individuals diagnosed early and those who receive proper treatment. Children with beta thalassemia major live 20-30 years longer with treatment by blood transfusions and iron chelation therapy.



Bowden, Vicky R., Susan B. Dickey, and Cindy Smith Greenberg. Children and Their Families: The continuum of care. Philadelphia: W.B. Saunders Company, 1998.

"Thalassemias." In Principles and Practice of Medical Genetics, Volume 2, edited by Alan E.H. Emery, MD, PhD, and David L. Rimoin, MD, PhD. New York: Churchill Livingstone, 1983.

Thompson, M.W., R. R. McInnus, and H. F. Willard. Thompson and Thompson Genetics in Medicine, Fifth Edition. Philadelphia: W.B. Saunders Company, 1991.


Angelucci, E., et al. "Hepatic iron concentration and total body iron stores in Thalassemia Major." The New England Journal of Medicine 343, (2000): 327-331.

Mentzer, W. C., et al. "Prospects for research in hematologic disorders: sickle cell and thalassemia." The Journal of The American Medical Association 285 (2001): 640-642.

Olivieri, N. F. "The Beta Thalassemias." The New England Journal of Medicine 341 (1999): 99-109.

Olivieri, N. F. et al. "Treatment of thalassemia major with phenylbuyrate and hydroxyurea." The Lancet 350 (1997): 491-492.


Children's Blood Foundation. 333 East 38th St., Room 830, New York, NY 10016-2745. (212) 297-4336. [email protected].

Cooley's Anemia Foundation, Inc. 129-09 26th Ave. #203, Flushing, NY 11354. (800) 522-7222 or (718) 321-2873. <>.

March of Dimes Birth Defects Foundation. 1275 Mamaroneck Ave., White Plains, NY 10605. (888) 663-4637. [email protected]. <>.

National Heart, Lung, and Blood Institute. PO Box 30105, Bethseda, MD 20824-0105. (301) 592-8573. [email protected]. <>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <>.

Laith F. Gulli, MD

Tanya Bivens, BS