Thalassemia: Awareness could save your future generation.

Jihan Noor

Jihan Noor

Article Written by Jihan Noor for Biomed Middle East

Thalassemia which is an inherited blood disease has been a cause of concern over the past few years due to its increased incidence. It is estimated that around 60-80 million people in the world carry the thalassemia trait. This is a very rough estimate and the actual number of thalassemia major patients is unknown due to the prevalence of this disease in less developed countries in the Middle East and Asia where genetic screening resources are limited. One in twelve people in the UAE carry the gene for Thalasemia according to figures collated by the Dubai Health Authority.

Countries such as India,Pakistan and Iran are seeing a large increase of thalassemia patients due to lack of genetic counseling and screening. There is a growing concern that thalassemia may become a very serious problem in the next 50 years, one that will burden the world bank supplies and the health system in general. There are an estimated 1000 people living with Thalassemia major in the United States and an unknown number of carriers. Because of the prevalence of the disease in countries with little knowledge of thalassemia,access to proper treatment and diagnosis can be difficult.

What is thalassemia?

Thalassemia is a genetic blood disorder. People with thalassemia are not able to make enough hemoglobin which causes severe anemia. Hemoglobin is found in red blood cells and carries oxygen to all body parts. When there is not enough hemoglobin in RBC, oxygen cannot get to all parts of the body. Organs then become starved of oxygen and are unable to function properly. 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 ‘thalassa’.

What causes thalassemia?

hemoglobin-molecureHemoglobin is an iron rich protein.It is composed of heme and two kinds of protein chains:alpha globin and beta globin.If your body doesn’t make enough of these protein chains,the hemoglobin becomes defective and the RBC don’t form properly and cant carry enough oxygen.

Below is a karyotype, a picture of all of an individual’s genetic information . Notice there are 22 pairs of numbered chromosomes (autosomes) and one pair of sex-determining chromosomes.


chromosome-11-16Genes control the globin chain synthesis.The alpha globin chain is coded by genes present on chromosome 16.They are present in duplicate,two genes on each chromosome 16,for a total of four.The genes that code for beta globin chain are present on chromosome gene on each chromosome, for a total of two.

In Thalassemia patients, mutations of the genes that control globin production, occurs. Mutations usually involved are substitution(switching of one nucleotide for another) or deletions(part of the chromosome is missing).This leads to a decreased production of corresponding globin chains and abnormal hemoglobin ratio. This abnormal ratio leads to decreased synthesis of hemoglobin and expression of thalassemia. The globin that is produced in normal amounts winds up in excess and forms red cell aggregates or inclusions. These aggregates become oxidized and damage the cell membrane leading either to hemolysis,ineffective erythropoiesis or both.

What are the types of Thalassemia?

Alpha thalassemia
Alpha thalassemia occurs when one or more of the four genes that are vital to making alpha globin chain are missing or damaged. There are four subtypes of alpha thalassemia. Each type represents the loss of or damage to one, two, three, or four genes.

  • One gene: If one alpha-globin gene is missing or damaged, you will have no symptoms and will not need treatment. But you are a silent carrier. This means you don’t have the disease but you can pass the defective gene onto your child. Smaller-than-normal blood cells may be the only sign of the condition.
  • Two genes: If two alpha-globin genes are missing or damaged, you will have very mild anemia that will not need treatment. This is known as alpha thalassemia minor or alpha thalassemia trait.
  • Three genes: If three alpha-globin genes are missing, you will have mild to moderately severe anemia. This is sometimes called hemoglobin H disease, because it produces a heavy hemoglobin. The body removes this heavy hemoglobin faster than it does normal hemoglobin. The more severe forms may need treatment with blood transfusions.
  • Four genes: If all four alpha-globin genes are missing (alpha thalassemia major), the fetus will be stillborn or the child will die shortly after birth.1 The hemoglobin produced by this condition is sometimes called hemoglobin Barts.

inheritance-pattern-alpha-thalessamiaInheritance Pattern for Alpha Thalassemia.

The diagram shows one example of how alpha thalassemia is inherited. The alpha globin genes are located on chromosome 16.

A child inherits four alpha globin genes—two from each parent. In this example, the father is missing two alpha globin genes and the mother is missing one alpha globin gene.

Therefore, each child has a 25 percent chance of inheriting two missing genes and two normal genes (thalassemia trait), three missing genes and one normal gene (hemoglobin H disease), four normal genes (no anemia), or one missing gene and three normal genes (silent carrier).

Beta thalassemia

Beta thalassemia occurs when one or both of the genes that produce beta-globin are mutated. There are several subtypes of beta thalassemia. Which type you have depends upon whether one or both genes are affected and whether those genes still produce some working beta-globin.

  • If you have one damaged beta-globin gene, you may have mild anemia and probably will not need treatment. This condition is called beta thalassemia minor or beta thalassemia trait. You have thalassemia trait when you inherit a normal gene from one parent and a thalassemia gene from the other.
  • When both beta-globin genes are damaged, moderate or severe anemia may develop. In this situation, you have inherited a thalassemia gene from each parent.
  • If you have moderate anemia (beta thalassemia intermedia), you may need blood transfusion. People who have beta thalassemia intermedia usually live into adulthood.
  • People with severe anemia (called beta thalassemia major or Cooley’s anemia) usually will not live into adulthood without treatment. Symptoms of anemia usually develop within 6 months of birth.1 If the child starts receiving blood transfusions early and continues to receive them throughout life, he or she is likely to live longer. Death is usually a result of damage to organs, such as the heart or liver. Lack of oxygen or an iron overload from blood transfusions causes the organ damage.


Inheritance pattern for beta thalassemia.

The diagram shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes—one from each parent.

In this example, each parent has one altered beta globin gene.

Therefore, each child has a 25 percent chance of inheriting two normal genes (no anemia), a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia trait), or a 25 percent chance of inheriting two altered genes(beta thalassemia major).

What are the symptoms?

Mild thalassemia usually does not cause any symptoms. But symptoms of anemia may develop in more severe forms of the condition and may include:

  • Weakness.
  • Fatigue.
  • Lightheadedness.
  • Skin that looks paler than normal.
  • Jaundice (skin and whites of the eyes appear yellow).
  • Dark urine.
  • Decreased appetite and weight loss (poor growth in a child).
  • A rapid heartbeat.
  • Shortness of breath during exercise.

How is thalassemia diagnosed?

A physical exam and complete medical history are usually the first steps in diagnosing thalassemia. Tests that help confirm a diagnosis of thalassemia include:

  • Complete blood count (CBC) and blood smear.
  • Gene test.
  • Iron level test, to determine whether iron deficiency anemia is present.
  • A blood test that measures the amounts of different types of hemoglobin (hemoglobin electrophoresis), to help find out which type of thalassemia you have.
  • A complete blood count (CBC) test on other members of your family (parents and siblings), to discover whether they may also have thalassemie.

How is it treated?

Blood Transfusions
Transfusions of red blood cells are the main treatment for people who have moderate or severe thalassemias. A blood transfusion, given through a needle in a vein, gives you healthy red blood cells with normal hemoglobin. Red blood cells live for only about 120 days. So, you may need repeated transfusions to maintain a supply of healthy red blood cells.

If you have hemoglobin H disease or beta thalassemia intermedia, you may need blood transfusions on occasion. For example, you may need this treatment when you have an infection or other illness, or when your anemia is severe enough to cause tiredness.

If you have beta thalassemia major, or Cooley’s anemia, you need regular blood transfusions (often every 2 to 4 weeks). These will help you maintain normal hemoglobin levels and red blood cell numbers. Blood transfusions allow you to feel better, enjoy normal activities, and live into adulthood.

Blood transfusions are lifesaving, but they’re expensive and carry a risk of transmitting infections and viruses (for example, hepatitis).

Iron Chelation Therapy

Because the hemoglobin in red blood cells is an iron-rich protein, regular blood transfusions can lead to a buildup of iron in the blood. This condition is called iron overload. It damages the liver, heart, and other parts of the body.
To prevent this damage, iron chelation therapy is needed to remove excess iron from the body. Two medicines are used for iron chelation therapy.

• Deferoxamine is a liquid medicine that’s given slowly under the skin, usually with a small portable pump used overnight. This therapy takes time and can be mildly painful. Side effects include loss of vision and hearing.
• Deferasirox is a pill taken once a day. Side effects include headache, nausea (feeling sick to the stomach), vomiting, diarrhea, joint pain, and fatigue (tiredness).

Folic Acid Supplements

Folic acid is a B vitamin that helps build healthy red blood cells. You may need to take folic acid supplements in addition to blood transfusions and/or iron chelation therapy.

Any possible cure for thalassemia?

Stem Cell Transplantation

Stem Cells, present in the bone marrow, give rise to red blood cells that produce Hemoglobin. In Thalassemia, it’s the defect in the stem cells that leads to deformed red blood cells that produce the abnormal hemoglobin and transfusion – dependent anemia. Stem Cell transplantation provides a thalassemia patient with healthy stem cells that will produce normal blood cells.

Stem Cells can be transplanted into a patient’s body through different methods, such as :

Bone Marrow Transplantation (Bmt)

In BMT, chemotherapy is used to kill the patient’s stem cells in the bone marrow. They are then replaced with healthy stem cells from a compatible donor. Bone marrow transplants are generally most successful when the donor and host are genetically compatible and when the patient is younger and less transfused.

Cord Blood Transplantation

Instead of harvesting stem cells from a donors bone marrow or blood, stem cells are taken from the “cord blood” found in the umbilical cord/placenta of a newborn sibling. Unlike regular bone marrow transplantation, the stem cells taken from the cord blood do not have to be a perfect genetic match. There appears to be a lower instance of rejection in cord blood transplantation.

Gene Therapy

The objective of GENE therapy is to insert a normal beta – globin gene into the patients stem cells, thus allowing increased production of beta globin and healthy red blood cells


Hemoglobin is composed of two protein chain-alpha globin chain and beta globin chains. Patients with beta-thalassemia do not make beta globin, they often require frequent red blood cell transfusions.

Some drugs, including hydroxyurea, can stimulate production of a third type of protein chain called gamma chains. In the womb, the foetus makes this type of protein instead of beta globin. It is not until after birth, when the foetus no longer produces gamma globin that the beta globin deficiency becomes apparent.

Hydroxyurea has been shown to induce production of fetal hemoglobin. Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia. Effects in patients with -thalassemia major are controversial. We now report a marked elevation of total Hb levels with HU that permitted regular transfusions to be stopped in some children with transfusion-dependent -thalassemia.


Living with thalassemia can be a challenge but following the recommended treatment plan,getting medical care regularly and adopting measures to stay healthy has definitely shown to increase life expectancy.Genetic counseling plays a very important role in disease management.Genetic counseling is a communication process to provide information and support to families that are in some way impacted by inherited diseases such as thalassemia.A genetic counselor usually conducts a pedigree analysis(detailed family medical history)which can help family members who maybe at risk of having thalassemia disease or trait to be tested and ensure their status. Partner testing and prenatal testing options would be considered for those families who have a famility history of the disease and who are planning to have a child. This could certainly help in early recognition and prevention of this disease.