How Much Do You Know About Thalassemia?

Overview

Thalassemia is a genetic blood disorder affecting the production of red blood cells. Abnormal production of blood means that affected individuals do not make adequate amounts of functional red blood cells. ^1,2
Thalassemia is caused by mutations in the DNA of cells that make hemoglobin — the substance in RBC that is responsible to carry oxygen throughout the human body. In addition, hemoglobin molecules are made of chains called alpha and beta chains that can be affected by mutations. ²
As it’s an inherited disorder, the mutations associated with thalassemia are passed from parents to children.¹

What are the different types of thalassemia?

To know about different “types” of thalassemia, it is vital to understand two concepts: the specific part of hemoglobin that is affected (usually either “alpha” or “beta”), and the severity of thalassemia, which is marked by the terms like trait, carrier, intermedia, or major., the production of either the alpha or beta chains is reduced, resulting in either alpha-thalassemia or beta-thalassemia. ²
In alpha-thalassemia, the severity of thalassemia an individual acquires depends on the number of gene mutations he/she inherits from the parent/ parents. The more mutated genes, the more severe the thalassemia. In beta-thalassemia, the severity of thalassemia an individual inherits depends on the genotype or the amount of defective beta-globin gene alleles. ^1,2
Clinically, patients with thalassemia can present with thalassemia minor or thalassemia major. ³

• Thalassemia Minor- Thalassemia minor, or Thalassemia trait, occurs when the person is a carrier of the thalassemia gene. These individuals inherit the thalassemia gene from only one parent and have a normal functioning hemoglobin gene from the other parent. While thalassemia minor patients do have a lower red cell count than normal, most of them are healthy and lead a normal life, as they are able to produce sufficient hemoglobin for the body to function. ^1-3
  However, the affected person can pass on the abnormal gene to their children.
  
• Thalassemia Major- Thalassemia major is a fatal form of anemia. It occurs when the individual has inherited two thalassemia genes (one from each parent). These individuals suffer from severe anemia from an early age and often require life-long blood transfusion support. Patients with Thalassemia Major suffer from poor growth and development as children. With time, these individuals may also experience iron overload due to repeated blood transfusions, which can cause damage to their organs, including the heart and liver. Thereby, individuals who have Thalassemia Major have a shorter lifespan. ^1,2
  

Signs & Symptoms of Thalassemia

The symptoms of thalassemia vary from individual to individual. Few individuals may exhibit no visible symptoms, while others may develop symptoms later in adolescence. Some of the most common symptoms include fatigue, weakness, pale or yellowish skin, bone deformities, especially facial features, delayed growth and development, abdominal swelling, and dark urine. ⁴


Complications

Possible complications of moderate to severe thalassemia include the following:-
1. Iron overload- Individuals with Thalassemia Major can get too much iron in their bodies, either from the disease or from frequent blood transfusions. As we all know, the excess amount of iron may damage organs like the heart, and liver. It can also lead to disturbances in the endocrine system, which includes hormone-producing glands that regulate processes throughout your body.
2. Infection. People with thalassemia have an increased risk of infection.
3. Bone deformities. Thalassemia can expand bone marrow, which leads to the widening of the bones. This can result in abnormal bone structure or bone deformity. Bone marrow expansion also makes bones thin and brittle, increasing the probability of fractures.
4. Enlarged spleen. Thalassemia is often accompanied by the destruction of a large number of red blood cells and can lead to splenomegaly.

Why should one go for Thalassemia Screening?

As thalassemia can be passed on from one generation to another, you and your partner should go for a thalassemia screening if you are:

• Planning to start a family
  
• Have a family history of thalassemia
  
• One of you is already diagnosed with thalassemia
  Thalassemia screening involves a simple blood test that is readily available. Studies are needed to better understand this risk.
  

  Diagnosis of Thalassemia

  Thalassemia may be anticipated based on family history, or it may be a new diagnosis for a family. Genetic testing to sequence point mutations or identify deletions is the definitive way to diagnose thalassemia and can be helpful in qualifying which mutations families harbor. CBCs will show varying degrees of microcytosis and hypochromia of RBCs, and anemia will vary depending on the underlying thalassemic condition.
  Dr. Dangs Lab carries out several laboratory tests to screen and diagnose thalassemia:-
  
• Complete blood count (CBC): CBC is often the first investigation in a suspected case of thalassemia. A CBC showing low hemoglobin and low MCV is the first indicator of thalassemia, after ruling out iron deficiency as the cause of anemia.
  
• Peripheral blood smear: A blood smear to assess red cell properties is very important. Thalassemia can present with the following findings on the peripheral blood smear:
  1. Microcytic cells (low MCV)
  2. Hypochromic cells
  3. Variation in size and shape (anisocytosis and poikilocytosis)
  4. Increased percentage of reticulocytes
  5. Target cells
  6. Heinz bodies
  
• Iron studies (serum iron, ferritin, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), and percent saturation of transferrin) are also done to rule out iron deficiency anemia as the underlying cause or concomitant finding.
  
• Erythrocyte porphyrin levels- Aids to distinguish an unclear beta-thalassemia minor diagnosis from iron deficiency or lead poisoning. Individuals with beta-thalassemia will have normal porphyrin levels, but those with the latter conditions will have elevated porphyrin levels.
  
• High-performance liquid chromatography (HPLC) on fresh lysates is the standard test for the identification of thalassemia. The hallmark of classical beta-thalassemia trait is the presence of an elevation of Hb A2, where the recommended method of measurement is automated HPLC. HPLC is a sensitive and precise method for the identification of Hb A2, Hb F, and abnormal hemoglobin. It has become the method of choice for thalassemia screening because of its speed and reliability. ^5,6
  
Newborn screening involves evaluation of Hgb production shortly after birth. Homozygous β thalassemia will have 100% fetal Hgb on newborn screen with complete absence of HbA. All other forms of β-thalassemia cannot be identified at birth and a test should be conducted after 6 months of age when a beta heterozygote/ thalassemia trait will often show elevated levels of HbA2 and HbF. In alpha-thalassemia, depending on the severity, variable amounts of Hb Barts (at birth and is seen till first 3-6 months) and HbH (starts appearing after 3 months of age) can be detected on Hb-HPLC. However, in the older child, the Hgb electrophoresis will appear normal with the α-thalassemia trait. The presence of HbH supports the diagnosis of HbH disease. ⁷


Are there any activities to avoid if one has Thalassemia?

There are no such restrictions. In most cases, individuals with Thalassemia Minor have no fitness or health issues. However, individuals with Thalassemia Major may have trouble taking part in vigorous forms of exercise. They might participate in moderate physical activities, including running and walking. But if their thalassemia is severe or/and associated with complications- under such circumstances they enact as an immunocompromised individual and end up staying most of the time indoors or in hospital. ^1,2


What is the life expectancy of someone with Thalassemia?

A person with the thalassemia trait has a normal life expectancy. However, heart complications arising from Thalassemia major can make the condition fatal and life-threatening too. ³


Treatment

The type of treatment a person receives depends on how severe the thalassemia is. The more severe the thalassemia, the less hemoglobin the body has, and the more severe the anemia may be. ^1-7
• Blood Transfusion : One way to treat anemia is to provide the body with more red blood cells to carry oxygen. This can be done through a blood transfusion, a safe, common procedure. Some people with thalassemia – usually with thalassemia major – need regular blood transfusions because their body makes such low amounts of hemoglobin. People with thalassemia intermedia (not as severe as major, but not as mild as a trait) may need blood transfusions sometimes, such as when they have an infection or an illness. People with thalassemia minor or trait usually do not need blood transfusions because they either do not have anemia or have only a mild anemia.
• Bone Marrow / Stem Cell Transplant: A bone marrow/stem cell transplant replaces the damaged stem cells with the healthy stem cells from a compatible donor. At present, this is the only treatment that can cure Thalassemia and drop the need for lifelong blood transfusions.
• Gene Therapy: Thalassemia gene therapy is currently undergoing clinical trials. Gene therapy aims to achieve a stable introduction of normal hemoglobin genes into the stem cells in the bone marrow. This will allow people who have thalassemia to make their own healthy red blood cells and hemoglobin.4
Many times, people with thalassemia are prescribed a supplemental B vitamin, known as folic acid, to help treat anemia. Folic acid can help red blood cells develop. Treatment with folic acid is usually done in addition to other therapies.

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Summary