A genetic blood disorder affecting hemoglobin production

Thalassemia is a genetic blood disorder that affects the production of hemoglobin. Hemoglobin is the part of a red blood cell (RBC) that carries oxygen to the tissues of the body. Normal adult hemoglobin is made up of 4 protein chains: there are 2 alpha chains and 2 beta chains. There are various degrees of severity of thalassemia that are caused by abnormal genetic coding of these alpha and beta chains.

Inheritance of Thalassemia

When a parent carries an altered gene that results in decreased quantities of alpha or beta protein to be made (or in some cases, where no alpha or beta protein is made), there is a chance that they will pass their thalassemia gene onto their children. This inheritance happens purely by chance – there is nothing parents can do (or not do) to stop their child from inheriting the gene for thalassemia. Genetic counseling is available at our center for couples who carry the thalassemia trait.

Alpha Thalassemia

Alpha thalassemia is caused by problems in the production of alpha protein chains. There are 2 genes on chromosome 16 that code for making alpha protein chains, each person carries 4 alpha genes (abbreviated αα/αα). The severity of the alpha thalassemia depends on the combination of abnormal genes that direct the production of the alpha protein.


  • 4 normal genes for alpha protein production


  • 3 normal genes with one missing or defective alpha protein gene
  • This is called alpha thalassemia minima, silent carrier of alpha thalassemia
  • Individuals usually do not have symptoms
  • Most individuals are diagnosed only with specialized DNA blood tests after another family member has been diagnosed

αα/-- or α-/α-

  • Two normal genes with two missing or abnormal alpha protein genes
  • This is called alpha thalassemia minor
  • May be associated with mild anemia (low hemoglobin)
  • Red blood cells (RBC) may be small and pale by microscope review


  • One normal gene with three missing or defective alpha protein genes
  • This is called hemoglobin H (HbH) disease 
  • Small quantities of alpha proteins are made, along with increased quantities of beta proteins
    • The extra beta chains group together in fours to make hemoglobin H
  • Hemoglobin H is not very effective at transporting oxygen and cause the membrane of the red blood cell to break open
    • This results in a hemolytic anemia (low red blood cell count) because the red blood cells break open and are destroyed
    • Individuals can develop large spleens and  often require splenectomy
    • Clinical severity varies widely, from some individuals with severe anemia, to some individuals who rarely have symptoms. Approximately 30-50% of individuals with HbH disease have received at least one transfusion.
    • Iron overload can become an issue and is treated with iron chelating agents
    • There are varying degrees and types of Hemoglobin H disease, including Hemoglobin H-constant spring, that can be further discussed with your health care provider


  • No normal genes are present. All four genes that code for alpha protein production are either missing or defective
  • This form of the disorder is called alpha thalassemia major
  • With this condition, no alpha protein is produced
  • This form almost always results in fetal death during the late second to mid-third trimester
    • Very rarely live births have been reported; however, this condition leads to hydrops fetalis and these infants usually die within a few hours after birth
    • Mothers that carry children with this disorder are at risk for severe pregnancy and delivery complications

Beta Thalassemia

Beta thalassemia is due to abnormal production of beta protein chains.  Each individual carries 2 beta genes. The severity of the disorder depends on the combination of genes the individual inherited from their parents.

There are more than 30 different genetic mutations that code for a decreased amount of beta protein to be made; and there are more than 40 different genetic mutations that code for no beta protein to be made. As a result, this disease is highly variable in terms of symptoms and severity.

β/β+ or β/β-

  • Beta thalassemia minima, also known as beta thalassemia trait (a subtype of beta thalassemia minor)
  • The individual inherited one gene that codes for decreased or absent beta protein production; and one gene that is normal
  • The individual usually does not have any symptoms except mild anemia

β+/β+ or β+/β0

  • Beta thalassemia intermedia (a subtype of beta thalassemia minor)
  • A disease of intermediate severity
  • The individual inherited genes from both parents that code for decreased production of beta protein
  • The individual is anemic, but usually only requires transfusions during episodes of acute illness, such as an infection, which can slow normal manufacturing of red blood cells. Clinical severity varies, and some patients become transfusion-dependent in their 30’s and 40’s.


  • Beta thalassemia major (also known as Cooley’s Anemia)
  • The individual inherited genes from both parents that code for no beta protein to be made
  • The individual is unable to make any normal adult hemoglobin
  • The individual suffers from severe anemia
    • Dependent on blood transfusions starting in the first year of life
    • Frequent blood transfusions cause excess iron to build up in the body
    • Require special medication called iron chelators (Exjade, Desferal) to remove the excess iron from their blood and tissues

How the IHTC can help you

The IHTC is committed to providing expert care for infants, children, teens, and adults with thalassemia. As a center of excellence in the treatment of bleeding and clotting disorders, the IHTC offers a high level of coordinated care for patients with this disorder. We also provide prompt communication with your local healthcare provider related to our treatment plan and your progress. The IHTC team collaborates with national experts and patient participation in research studies may be available.

At the IHTC we have clinicians who are experts in treating thalassemia and providing support to patients with this disorder. As every patient can experience a different rate of disease progression and different symptoms it is very important that you are seen by a clinician who is familiar with the signs and treatment of thalassemia. We can help you with diagnosis, testing and treatment; and can provide dietary, genetic and general counseling depending on your specific needs. For more information, please contact us at 877.CLOTTER (877.256.8837).


Contact Us

If you are in Indiana, call
317.871.0000 or 877.CLOTTER (877.256.8837)