Thalassemia

Thalassemia is an inherited blood disorder that disrupts the body’s ability to make healthy red blood cells. These cells normally carry oxygen throughout the body, but in thalassemia, fewer healthy red blood cells are produced. This shortage leads to anemia, a condition in which the body doesn’t have enough oxygen-carrying red blood cells.

How Thalassemia Affects the Body

Hemoglobin, a protein within red blood cells, is essential for oxygen transport. In this inherited blood disorder, genetic mutations prevent the body from creating enough normal hemoglobin. This results in fewer healthy red blood cells being produced by the bone marrow. The lack of sufficient oxygen delivery to tissues can cause various symptoms, including fatigue, shortness of breath, feeling cold, dizziness, and pale skin.

Severity and Risk Factors

Thalassemia can range from mild to severe anemia. In some cases, it can also lead to iron overload, a complication arising from excess iron buildup in the body. Interestingly, the genetic mutations that cause this inherited blood disorder may have originally offered some protection against malaria in certain populations. This is why people with ancestors from areas where malaria was common, such as parts of Africa, Asia, and Southern Europe, have a higher risk of inheriting this blood disorder.

Genetic Inheritance

Thalassemia is passed down from parents to children. The specific genes that provide instructions for making the protein chains of hemoglobin, alpha and beta globin, are affected in thalassemia. Two alpha globin chains and two beta globin chains combine to form hemoglobin, making it four chains in total. These chains contain genetic information inherited from both parents. Defects or missing genes in either the alpha or beta globin chains can cause this inherited blood disorder. The severity of the condition depends on the seriousness of the genetic defect in these chains.

Types of Thalassemia

Doctors categorize this inherited blood disorder into different types based on the severity of the condition. These types are trait, minor, intermedia, and major. These classifications indicate the range of symptoms experienced, from mild to severe. Individuals with this inherited blood disorder trait may have minimal or no symptoms and may not require treatment, while those with this inherited blood disorder major typically require ongoing medical care.

There are two main types of thalassemia: alpha thalassemia and beta thalassemia, named after the specific defects in the alpha and beta globin protein chains.

Alpha Thalassemia:

In alpha thalassemia, you inherit four genes, two from each parent, responsible for producing alpha globin protein chains. The number of defective genes inherited determines the severity of symptoms.

• One defective or missing alpha gene typically results in no symptoms, also known as alpha thalassemia minima.
• Two defective or missing alpha genes may lead to mild symptoms, termed alpha thalassemia minor.
• Three defective or missing alpha genes can cause moderate-to-severe symptoms, known as hemoglobin H disease.
• When someone inherits all four alpha genes in a defective or missing state (a very rare event), this extremely serious condition is called hydrops fetalis with hemoglobin Barts.

Beta Thalassemia:

In beta-thalassemia, you inherit two beta-globin genes, one from each parent. The severity of symptoms depends on the number of defective genes and the location of the defect in the beta-globin protein chain.

• One defective or missing beta gene usually results in mild symptoms, termed beta thalassemia minor.
• Two defective or missing beta genes can lead to moderate to severe symptoms. Thalassemia intermedia is the moderate form, while beta-thalassemia major, or Cooley’s anemia, is the more severe version.

Symptoms of thalassemia

The symptoms of this inherited blood disorder can vary depending on the type and severity of the condition.

Asymptomatic (no symptoms):

• If you’re missing one alpha gene, you’re likely to have no symptoms.
• Individuals missing two alpha genes or one beta gene may also be asymptomatic or experience mild anemia symptoms like fatigue.

Mild to Moderate Symptoms:

• Beta thalassemia intermedia may cause mild anemia symptoms or other signs such as:
• Growth issues.
• Delayed puberty.
• Bone abnormalities like osteoporosis.
• Enlarged spleen, which may require surgical correction or removal if it becomes too large.

Severe Symptoms:

• Missing three alpha genes, known as hemoglobin H disease, often leads to severe lifelong anemia, noticeable from birth.
• Beta thalassemia major, also called Cooley’s anemia, typically manifests severe anemia symptoms by age 2.
• Symptoms of severe anemia can include those seen in mild to moderate cases, along with:
• Poor appetite.
• Pale or yellowish skin (jaundice).
• Dark or tea-colored urine.
• Irregular bone structure in the face.

Diagnosis of thalassemia

• Moderate and severe forms of this inherited blood disorder are usually diagnosed in childhood, as symptoms typically appear within the first two years of life.
• Diagnostic tests may include:
• Complete blood count (CBC) to assess hemoglobin levels and red blood cell count.
• Reticulocyte count to evaluate bone marrow function.
• studies to differentiate between iron deficiency anemia and thalassemia.
• Hemoglobin electrophoresis for diagnosing beta thalassemia.
• Genetic testing for diagnosing alpha-thalassemia.

Treatment and Management

This major inherited blood disorder typically requires a combination of treatments to manage the condition effectively.

1. Blood Transfusions:
   • Blood transfusions involve receiving injections of red blood cells to restore healthy red blood cell levels and hemoglobin.
   • For moderate to severe thalassemia, transfusions are typically administered every four months, while for beta thalassemia major, they are needed every two to four weeks.
   • Occasional transfusions may be necessary during times of infection for individuals with hemoglobin H disease or beta thalassemia intermedia.
2. Iron Chelation Therapy:
   • Iron chelation therapy is used to remove excess iron from the body, which can accumulate due to frequent blood transfusions and lead to organ damage.
   • This therapy is often administered orally in the form of pills to prevent iron overload.
3. Folic acid supplements:
   • Folic acid supplements can aid in the production of healthy blood cells and are commonly prescribed to individuals with thalassemia.
4. Bone Marrow and Stem Cell Transplants:
   • A bone marrow or stem cell transplant from a compatible donor is the only curative treatment for thalassemia.
   • Compatibility is determined by matching human leukocyte antigens (HLA) between the donor and recipient.
   • During the transplant procedure, stem cells from the donor are injected into the recipient’s bloodstream, where they start producing healthy blood cells.
5. Luspatercept Treatment:
   • Luspatercept is an injection administered every three weeks to stimulate the production of red blood cells.
   • It is approved for the treatment of transfusion-dependent beta-thalassemia in the United States.

Complications of thalassemia

1. Iron Overload:
   • Excessive iron accumulation in the body, resulting from frequent blood transfusions or the disease itself, can lead to organ damage, particularly affecting the heart, liver, and endocrine system.
   • The endocrine system regulates various bodily processes through hormone production.
2. Increased Risk of Infections:
   • Individuals with thalassemia, especially those receiving frequent blood transfusions, are at a higher risk of developing severe infections.
   • Careful screening of donor blood during transfusions is essential to prevent the transmission of infections through blood transfusions.

Prevention

Thalassemia cannot be prevented, but genetic testing can identify whether you or your partner carry the gene for the condition. This knowledge is valuable for family planning, especially if you are considering pregnancy. Consulting a genetic counselor can provide guidance on planning a pregnancy and managing the risk of passing this inherited blood disorder on to your children.

Outlook/Prognosis

• Cure: A bone marrow transplant from a compatible sibling offers the best chance of curing thalassemia. However, suitable sibling donors are often scarce, and the procedure carries high risks, including severe complications and even death. It’s essential to consult a thalassemia specialist to assess eligibility for a transplant. Opting for a hospital experienced in bone marrow transplants can increase the likelihood of a successful outcome while reducing risks.
• Life Expectancy: Individuals with mild thalassemia can expect a normal life expectancy. Even those with moderate or severe forms have good prospects for long-term survival by adhering to their treatment regimen, which typically includes transfusions and iron chelation therapy. Heart disease resulting from iron overload is the primary cause of mortality in these inherited blood disorder patients, emphasizing the importance of regular iron chelation therapy.

Living With thalassemia

Ongoing Care:

• Regular monitoring is crucial for managing this inherited blood disorder effectively. This includes frequent complete blood counts and blood iron tests, as well as periodic heart and liver function assessments.
• Testing for viral infections is recommended due to the increased risk associated with thalassemia.
• Annual assessments for iron overload in the liver are necessary to monitor and manage this complication.
• It’s essential to collaborate closely with healthcare providers to tailor ongoing care to the specific needs of your condition.

In conclusion, while thalassemia presents challenges, it is a treatable condition with proper management. Seeking appropriate medical care and staying proactive in monitoring and treatment can significantly improve the quality of life for individuals living with this inherited blood disorder. If there are plans for pregnancy and concerns about thalassemia genetics, consulting a genetic counselor is highly recommended for personalized guidance and support.