Alpha and Beta Thalassemia and Laboratory Tests


Thalassemia is a type of disorder that is blood inherited (passed down from parents to their children). This condition affects the amount and type of hemoglobin produced by the body.

Hemoglobin (abbreviated as Hgb or Hb) is a component that is found in the red blood cells (abbreviated as RBCs). The red blood cells need to function properly because it carries oxygen to different parts of the body. Hemoglobin is a vast compound, with different portions like: 

  • Heme – This is a molecule with iron at the center 
  • Globins – This is another portion that is made up of four protein chains (each globin in the chain holds a heme group, which contains one iron atom.) 

Depending on the structure, globin chains are labeled as delta, gamma, beta, or alpha. It is important to note that not all hemoglobin is the same. Each is classified depending on the globin chain type. Also, it is important to note that the type of globin chain plays a huge role in hemoglobin’s ability to transport oxygen. 

Normal Hemoglobin Types Include: 

  • Hemoglobin A – This Type of Hb is predominant in adults, and it makes up about 95%-98% of hemoglobin. It contains two beta and two alpha protein chains. 
  • Hemoglobin A2 – This type makes up about 2%-3.5% of Hgb found in adults. This type also has two delta and two alpha protein chains. 
  • Hemoglobin F – This type of Hgb makes up 2% of hemoglobin found in adults. This type also has two gamma and two alpha protein chains. 

Did you know that hemoglobin F is primarily produced by developing babies (fetus), while in the womb? Hb F production decreases to low levels within the first year after birth. 

A person with Thalassemia usually has one or multiple genetic mutations, which they have inherited. For this reason, it decreases the production of normal hemoglobin. The moment the body is not producing enough hemoglobin, the red blood cells will not function normally or deliver oxygen to the body effectively. This problem may cause anemia with symptoms and signs, ranging from mild to severe. It all depends on the type of thalassemia one has.  

Signs and symptoms may include: 

  • Fatigue 
  • Weakness 
  • Pale skin (pallor) 

There are four genes in our DNA when it comes to the hemoglobin, which code for the gamma-globin chains, two genes delta, two genes beta, and alpha-globin chains. Because everyone inherits a set of chromosomes from both parents, everyone receives two alpha globulin genes and a beta globulin gene. For this reason, a person can inherit a mutation in either beta or alpha-globin genes.  

The production of a low amount of a globin chain is caused by a mutation in one or several globin genes. Of course, when this happens, one should expect an imbalance of alpha to beta chains, which results in an unusual form of hemoglobin or an increased number of minor hemoglobin like Hgb F or Hgb A2. These thalassemias are generally classified by the type of globin chain whose synthesis is low.  

For example, the common alpha chain related condition is known as alpha thalassemia. The seriousness of this condition highly depends on the number of genes affected. Other types of mutations, such as globin chain genes coding, may result in a structurally altered globin. This may result in hemoglobin S, which causes sickle cell. This inherited condition, which causes the production of abnormal hemoglobin molecules, is fully described in an article talking about Hemoglobin Abnormalities. Both hemoglobin abnormalities and thalassemia are known as Hemoglobinopathies.

Alpha Thalassemia 

Alpha thalassemia is a result of either mutation or depletion of one or several alpha -globin genetic factor copies. It is important to note that alpha-globin production decreases due to mutation. The bigger the number of genes affected, the low alpha-globin the body will produce. All four types of alpha thalassemia are classified based on the number of genes affected. They include: 

  • Silent Carrier State (1 Gene Affected) 

Those who have a mutation(s) in only one alpha-globin gene are simply silent carriers. To such a person, they will have a normal hemoglobin level as well as a red cell profile. However, they can still pass on the affected gene to their children. Such a person will also not experience any signs or symptoms of the condition, and they are only identified after having a child with thalassemia. The only way to know if you are a carrier is through DNA analysis (check thalassemia tests). 

  • Alpha Thalassemia Trait (2 Genes Affected) 

A person with alpha thalassemia traits will have red blood cells that are hypochromic (paler) and microcytic (smaller) than that of a normal person. The red blood cell will also have a decreased mean corpuscular volume (MCV), which is a measurement of the average size of a single RBC. The person will also have mild chronic anemia. In most cases, a person with alpha thalassemia trait will not experience any other sings and a times lack symptoms.  

This form of anemia does not respond well to iron supplements. Alpha thalassemia trait should be done by eliminating other causes of microcytic anemia. Confirmatory testing through DNA analysis is available, but not mainly done. 

  • Hemoglobin H Disease (3 Genes Affected) 

With this condition, because there is a huge decrease in the alpha-globin chain, the number of beta chains becomes high. This ten comes together into a group of 4 beta chains, known as Hemoglobin H., this becomes visible in the red blood cells on a specially stained blood smear. Hgb H disease may cause moderate to severe anemia, which results in health problems like fatigue, bone deformities, and an enlarged spleen. Its symptoms or signs vary greatly. Some people are asymptomatic, while other people get serious anemia, needing constant medical care. This condition is mostly found in people of Mediterranean descent or Southwest Asian. 

  • Alpha Thalassemia Major Aka Hydrops Fetalis (4 genes affected) 

Hydrops Fetalis is the most severe form of alpha thalassemia. With this condition, the body does not produce any alpha globin, which means the body does not have normal hemoglobin. A majority of the unborn affected by alpha thalassemia during pregnancy become anemic. They frequently have larger hearts and livers. They also retain hydropic (excessive fluids). Pregnancy diagnosis is often conducted during the last months of the pregnancy.  

Pregnant mothers are also at risk. Research shows that mothers are at high risk of getting toxemia (high blood pressure, protein in the urine, swollen ankle, and feet). The mother may also develop severe hemorrhage (postpartum bleeding). Most fetuses with the severe case of alpha thalassemia are often miscarried, stillborn, or die shortly after birth. It is rare for a child with the alpha thalassemia major to survive through extensive medical care and Utero blood transfusions. This condition is most common to individuals of Mediterranean descent, African, Indian, middle eastern, southern Chinese, and Southeast Asian.  

Beta Thalassemia 

Beta thalassemia is a condition that is a result of a mutation in one or more beta-globin genes. There are more than 250 mutations that have been identified. However, only about 20 are the most common. The seriousness of anemia as a result of beta-thalassemia highly depends on the mutation itself and the degree of beta production. The different types of beta-thalassemia include: 

  • Beta Thalassemia Minor or Beta Thalassemia Trait 

A person with this condition will have one gene with a mutation and the other one normal. This causes a mild decrease in beta-globin production. In most cases, this condition does not bring any health problems other than abnormal small red blood cells and positive mild anemia that does not respond to iron supplements. Remember, this condition can be inherited.  

  • Thalassemia Intermedia 

A person with this condition has two abnormal genes, which causes moderate to a severe decrease in beta-globin production. Such a person may develop symptoms later in life than those of the thalassemia major, and the symptoms are mild. Such a person rarely requires treatment with blood transfusion. The seriousness of the health problems and anemia the person will receive will generally depend on the type of mutation. The dividing line between thalassemia major and thalassemia intermedia is the degree of anemia, the frequency, and the number of blood transfusions needed. However, blood transfusion is needed regularly to a person with thalassemia intermedia. 

  • Cooley’s Anemia or Thalassemia Major 

 This is the most severe condition of beta-thalassemia. A person suffering from this condition has two abnormal genes, which causes either a serious decrease or lack of beta-globin production. This prevents the production of high numbers of normal hemoglobin A. this condition will appear within the first two years of life and mainly leads to life-threatening conditions. It does also affect growth and skeletal abnormalities during infancy. These conditions need regular blood transfusions and considerable ongoing medical care.  

With time, the frequent transfusions cause an excessive amount of iron in the body. If it is left untreated, the excessive iron can be deposited in the heart, liver, and other vital body organs, which may lead to organ failure. For this reason, a person undergoing transfusion will need chelation therapy to reduce iron overload.  

This condition is commonly found in Africans, Mediterranean, and southeast Asian descendants in the US. This is because it is associated with the incidence of malaria in those areas because thalassemia can increase malarial tolerance. Therefore, in those areas, malaria thalassemia incidences are being as high as 10%. 

Other types of thalassemia happen when a gene for beta-thalassemia is inherited in combination with the hemoglobin gene. The most important of these are: 

  • Hb E-beta Thalassemia 

This is one of the most common hemoglobin variations. This condition is found specifically in people from the African and Southeast Asian descendants. Therefore, if a person inherits one beta-thalassemia gene and one Hb E gene, the combination produces Hb E-beta thalassemia, which causes moderate to severe anemia, which is like beta-thalassemia intermedia. 

  • Sickle Cell-beta Thalassemia or Hb S-beta Thalassemia 

This is a well-known condition of hemoglobin variants. Those who inherit one beta-thalassemia gene and one Hb S gene results in Hb S-beta thalassemia. With this condition, the severity depends on the amount of beta-globin that is produced by the beta gene. If beta-globin is not produced, clinical pictures are like sickle cell disease. 

Tests and Diagnosis 

Few laboratory tests can be used to detect and diagnose thalassemia: 

1. Complete Blood Count (CBC) 

This form of diagnosis is an evaluation of cells in the blood. Aside from other things, CBC determines the number of red blood cells and how much hemoglobin is in them. This diagnosis is used to evaluate the shape and size of the red blood cells available and reported as red cell indices. Diagnosis will include MCV (mean corpuscular volume) and a measurement of the red blood cells. The first indication of thalassemia is a low MCV. Howe? Well, if iron deficiency has been ruled out, but still the MCV is low, then a physician will consider thalassemia next. 

2.Blood Smear (similarly known as a peripheral smear and manual differential) 

With this laboratory test, the expert will examine a thin layer of blood which has been treated with a special stain under a microscope. From there, the professional will consider the number and types of platelets, red blood cells, and white blood cells to see if they are normal and mature. It is important to note that a person with thalassemia, the red blood cells will appear smaller than usual. It is also important to remember that red cells may also:

  • anisocytosis and poikilocytosis (vary in size and shape) 
  • hypochromic (appear paler than normal) 
  • have uneven hemoglobin distribution (producing cells that look like a bull’s eye) 
  • be nucleated (cells being normal, matured but do not have a nucleus) 

The higher the percentage the cells are found to be abnormal, the higher the chances of a person having the disorder and, therefore, cells losing its ability to circulate oxygen.  

3. Iron Testing 

This form of diagnosis or test may include ferritin, iron, UIBC (unsaturated iron-binding capacity), percentage saturation of transferrin, and TIBC (total iron-binding capacity). This diagnosis measures the ability of the body to store and use iron. This test is important because it helps determine if iron deficiency is the root cause of anemia. With this test, one or more tests may be conducted simply to monitor the degree of iron overload in a person with thalassemia.  

Often, iron deficiency anemia is confused with alpha thalassemia because both have similar cell characteristics. However, it is wise to note that iron levels are not expected to be low when someone has been diagnosed with thalassemia. As such, the person with alpha thalassemia will not benefit from iron therapy, and infarct may cause major body organs to fail due to iron overload.  

To differentiate beta-thalassemia minor from lead poisoning or iron deficiency: erythrocyte porphyrin test may be needed. A person will have normal porphyrin levels even if they have beta-thalassemia, but those with either lead poisoning or iron deficiency will have an elevated porphyrin reading. 

4. Hemoglobin Electrophoresis (Hemoglobinopathy (Hb) Evaluation)

This test aims to evaluate the kind, and the relative number of hemoglobin is present in the red blood cells. Hb A (Hemoglobin A) contains both the beta and alpha-globin, and it is a type of hemoglobin, which normally makes up about 97% of the hemoglobin in adults. Hemoglobin F usually makes up less than 2%, while Hb A2 (hemoglobin A2) usually takes up about 3% of hemoglobin in adults. 

People with beta-thalassemia major often have larger percentages of Hgb F. That is because beta-thalassemia affects the balance of alpha and beta hemoglobin chain formation greatly. It causes an increase in minor hemoglobin components. Also, remember that a person with beta-thalassemia minor often has a high number of Hgb A2. Hb S is dominant in persons with sickle cell disease. 

5. DNA Analysis 

This test is important and helps identify and confirm the mutation in beta and alpha globin-producing genes. This test is not routinely done but can be used to aid thalassemia diagnosis, as well as determine carrier status if indicated.  

The hemoglobin beta gene may be sequenced or analyzed to confirm the presence of mutations that may cause beta-thalassemia. Remember, there are more than 250 mutations that have been associated with beta-thalassemia, even though some do not come with signs or symptoms. On the other hand, some decrease the amount of beta-globin production while others prevent its production. The confirmation or discovery of those mutations is what confirms the diagnosis. 

The main molecular test available for alpha thalassemia helps confirm common mutations such as deletions. Remember, everyone has two copies of these genes known as alleles. One of the functions of alleles is governing the production of alpha-globin. Therefore, if mutation leads to functional loss of either one or more alpha genes, alpha thalassemia will occur. 

Because thalassemia is a condition that is passed down the generation, family education is wise so as they can evaluate or carry out studies to identify the types of mutations found within the family if found necessary by a HealthCare professional. 

Amniotic fluid genetic testing is used in rare cases or situations if found a fetus is at risk for thalassemia. This testing is crucial, especially when both parents are carriers of a mutation that puts the infants at risk. In a nutshell, this test often takes place if the case is severe.