What Is Beta Thalassemia?

Beta thalassemia is a blood disorder that affects the production of hemoglobin. Hemoglobin is the iron-rich protein in your red blood cells that carries oxygen throughout your body. With beta thalassemia, your body lacks sufficient amounts of healthy red blood cells with hemoglobin, and anemia develops, causing symptoms like fatigue, weakness, shortness of breath, and pale skin.

Beta thalassemia is an inherited (genetic) disorder that affects 1.5% people worldwide. It is most common in people with Mediterranean, Middle Eastern, African, Indian, and Asian ancestry. Depending on the type of beta thalassemia you have, symptoms can range from mild to severe and may begin shortly after birth or later in adulthood.

While beta thalassemia is a lifelong condition, treatment options such as blood transfusions, iron chelation therapy, and bone marrow transplantation, can help increase your levels of healthy red blood cells and hemoglobin and relieve symptoms.

Types

There are three main types of beta thalassemia: minor, intermedia, and major. Mutations (variants) in the HBB gene (the gene that controls the production of the beta-globin proteins that make up hemoglobin) cause each type of beta thalassemia. The number of HBB variants you inherit determines the type of beta thalassemia you have and the severity of your case.

Beta Thalassemia Minor (Trait)

Also known as beta thalassemia trait, people with beta thalassemia minor inherit only one HBB gene variant (mutation). Affected people usually do not experience symptoms—and if they do it is mild anemia—and rarely require treatment.

Beta Thalassemia Intermedia 

People with beta thalassemia intermedia inherit two HBB gene variants (mutations) and have lower levels of beta-globin than average. Anemia symptoms can range from moderate to severe, and some people with this type may require occasional treatments (e.g., blood transfusions).

Beta Thalassemia Major (Cooley's Anemia)

Also known as Cooley's anemia, beta thalassemia major occurs when you inherit two HBB gene variants (mutations), and your body produces very little or no beta-globin proteins. People with this type have severe anemia, with symptoms first developing during infancy. This typw requires regular blood transfusions and other treatments.

Symptoms 

The symptoms of beta thalassemia vary, depending on the type and severity of the condition. 

Beta Thalassemia Minor Symptoms

People with beta thalassemia minor rarely develop symptoms, and many are unaware they have the condition. Mild hemolytic anemia develops with beta thalassemia because the body breaks down red blood cells more quickly than usual. Symptoms of mild anemia can include: 

• Feeling tired or weak
• Dizziness
• Pale skin 
• Moodiness
• Shortness of breath  
• Weakness 
  

Beta Thalassemia Intermedia Symptoms

Symptoms of beta thalassemia intermedia often develop later in life and can range from moderate to severe. Common symptoms include:

• Paleness 
• Fatigue or tiring easily 
• Jaundice (yellowish-tinted skin) due to the rapid breakdown of red blood cells
• Shortness of breath
• Dizziness or lightheadedness 
• Dark-colored urine 
  

Some people with beta thalassemia intermedia may develop additional symptoms, such as:

• Abdominal swelling due to an enlarged liver and spleen 
• Bone deformities in the legs, arms, or face

Beta Thalassemia Major Symptoms

Beta thalassemia major is the most severe form of the condition, and symptoms typically appear within the first two years of life. Symptoms of beta thalassemia major, or Cooley's anemia, may include:

• Extreme fatigue
• Headaches
• Paleness
• Shortness of breath
• Rapid heart rate (tachycardia)
• Irritability or moodiness 
• Dark urine 
• Slow growth in infants and children
• Delayed puberty 
• Jaundice
• Abdominal swelling due to an enlarged spleen (splenomegaly) 
• Bone deformities 
• Facial differences, such as prominent cheekbones or forehead, depressed nasal bridge, overgrowth of the upper jaw 

Causes

Beta thalassemia is an inherited disorder, meaning it is passed down from parent to child.

Four "building blocks" make up hemoglobin: two alpha-globin subunits and two beta-globin subunits. The HBB (hemoglobin subunit beta) gene is part of a hemoglobin molecules. The HBB gene is responsible for the production of beta-globin proteins, which help your body produce more hemoglobin. With beta thalassemia, HBB gene mutations disrupt the production of beta-globin, leading to fewer hemoglobin molecules that your body can use.

Beta thalassemia is autosomal recessive, meaning both parents must carry the same gene mutations, called thalassemia traits, to have a child with the condition. If both parents are carriers of HBB gene mutations, their child has a:

• 50% chance of being an asymptomatic carrier
• 25% chance of being born with beta thalassemia intermedia or major
• 25% chance of receiving unaffected genes from both parents
  

The number of HBB gene mutations you inherit from your parents determines the type and severity of beta thalassemia you have. People with one gene mutation (carriers) experience no or minor symptoms, while those who inherit two or more will develop more severe anemia.

Risk Factors

Since beta thalassemia is genetic, having a family history of the condition increases your likelihood of having it or passing the gene mutations down to your children. People with certain ancestries have an increased risk of beta thalassemia:

• Mediterranean
• Middle Eastern
• African
• Indian
• Central or Southeast Asian  

Diagnosis

Prenatal testing can be used to diagnose beta thalassemia in an unborn child during pregnancy. Healthcare providers may recommend prenatal screening for beta thalassemia if both parents know they are genetic carriers of the condition. These tests include:

• Chorionic villus sampling (CVS): Performed between weeks 10 to 13 of pregnancy, this test involves taking a tissue sample from the placenta and testing it for mutations in the HBB gene.
• Amniocentesis: Performed between weeks 15 to 20 of pregnancy, this test involves inserting a thin needle into the pregnant person's abdomen and extracting a sample of amniotic fluid to test for beta thalassemia gene mutations. 
• Molecular genetic testing: While not necessary to diagnose beta thalassemia, molecular genetic testing can confirm the diagnosis or predict the risk and severity of beta thalassemia in a newborns. Your healthcare provider may recommend molecular genetic testing if you are pregnant and have a family history of beta thalassemia.
• Noninvasive prenatal testing (NIIPT): This type of testing is used for early evaluation of genetic conditions like thalassemia in unborn fetuses. However, it requires confirmation with invasive methods.
  

Otherwise, a diagnosis of beta thalassemia can occur at any point in your lifetime. When you visit your healthcare provider with symptoms of anemia, they may ask about your risk factors for beta thalassemia, including ancestry, family history of the condition, and personal medical history. 

Your healthcare provider will order blood tests to confirm a beta thalassemia diagnosis. For these tests, your provider will order a blood draw to obtain a blood sample and send it to the lab for testing. These blood tests may include:

• Complete blood count (CBC): This test measures the amount of red blood cells and hemoglobin in your blood. People with beta thalassemia have fewer red blood cells and less hemoglobin than normal.
• Hemoglobin electrophoresis: This test measures different types of hemoglobin proteins in your blood. Low levels of certain types of hemoglobin are a sign of beta thalassemia.
• Peripheral blood smear: This microscopic examination of your blood shows the size and shape of your red blood cells. People with beta thalassemia usually have smaller red blood cells than normal.
• Iron studies: This test measures iron levels in your blood to rule out iron-deficiency anemia, which causes symptoms similar to beta thalassemia-related anemia.

Treatments for Beta Thalassemia  

Treatments for beta thalassemia help increase red blood cell and hemoglobin levels to relieve anemia symptoms and prevent complications. You may not need treatment if you have a minor beta thalassemia minor with no or mild symptoms. People with more severe types of beta thalassemia may need regular treatments to increase red blood counts to control symptoms and reduce the risk of complications.

Blood Transfusions 

Blood transfusions are the most common treatment for people with beta thalassemia. This treatment involves receiving blood from a healthy donor through an intravenous (IV) line in one of your blood vessels, replenishing your red blood cells, and improving oxygen delivery to your body's cells. 

How often you need blood transfusions depends on the type of beta thalassemia and the severity of your symptoms.

With beta thalassemia intermedia, you may only need occasional blood transfusions, such as during pregnancy, when you have an infection, or after surgery. 

People with beta thalassemia major may need regular blood transfusions every 3 to 4 weeks to maintain healthy red blood cell and hemoglobin levels. 

Iron Chelation Therapy 

Your healthcare provider may prescribe iron chelation therapy if you receive regular blood transfusions as part of your beta thalassemia treatment plan. While regular blood transfusions are necessary to boost hemoglobin levels, they also increase the risk of excess iron in your body (iron overload). Iron chelation therapy helps your body remove extra iron to prevent serious, life-threatening complications of iron overload.

Medications for iron chelation therapy include:

• Desferal (deferoxamine): Liquid medication delivered subcutaneously (under the skin) through a small portable pump. It takes 8 to 12 hours to administer a full dose, so many people set the pump up to deliver the medicine while they sleep.
• Exjade (deferasirox): Taken in the form of a tablet that dissolves in water or juice you drink once a day. 
• Jadenu (deferasirox): An oral medication (pill) you swallow once daily on an empty stomach or with a light meal. 
• Ferriprox (deferiprone): If other iron chelation drugs are ineffective, your provider may prescribe Ferriprox, an oral medication (pill) you take three times a day. This medicine can have serious side effects such as lowering you white blood cell counts, which increases your risk of infection. 

Blood and Bone Marrow Transplant

A blood and bone marrow transplant (BMT) involves transplanting blood-producing stem cells from a healthy donor (who is a match for the person receiving the transplant) into the blood-producing tissue of a person with beta thalassemia. Over time, the transplanted donor stem cells produce new, healthy blood cells.

While a BMT is a possible cure for beta thalassemia, the process is complex and has many risks (e.g., rejection of donor cells). BMT is most commonly considered for people who meet certain criteria to reduce the risk of complications. The criteria include:

• Younger than 16 years old
• Have a healthy liver
• No signs of iron overload

Other Treatments

Your healthcare provider may recommend other treatments in addition to blood transfusions to help manage anemia symptoms related to beta thalassemia. These may include:

• Folid acid supplements: Vitamin B9 (folic acid) supplements may promote red blood cell development, which may help reduce anemia symptoms.
• Reblozyl (luspatercept): This is medicine that helps increase the number of healthy, mature red blood cells, reducing the amount of blood transfusions you need. 
• Splenectomy: The spleen helps filter and remove old, dead red blood cells. With beta thalassemia, small, abnormal red blood cells and iron can build up in the spleen, causing it to enlarge (splenomegaly). It can also become overactive, and you may need more blood transfusions than usual. When this occurs, your healthcare provider may recommend a splenectomy (surgical removal of the spleen) to manage symptoms and prevent complications.

Prevention

Because beta thalassemia is an inherited disorder, there is no definitive way to prevent it. If you have a family history of beta thalassemia or are considering having children, genetic testing can determine whether you and/or your partner are carriers for the condition.

A genetic counselor can explain your carrier status and the risk of passing the condition on to your children. Some beta thalassemia carriers may opt to undergo fertility treatments, such as in-vitro fertilization (IVF), which allows for preimplantation genetic diagnosis (PGD). PGD identifies embryos that would develop into a child with beta thalassemia before implantation, helping prevent passing the condition on.

Related Conditions 

People with beta thalassemia may develop other related conditions, such as:

• Iron overload: Regular blood transfusions can lead to iron buildup in your body, increasing the risk of damage to internal organs, including the liver and heart. 
• Diabetes: Beta thalassemia can affect how your body metabolizes blood sugar (glucose), increasing the risk of insulin resistance and type 2 diabetes.
• Osteoporosis: Chronic anemia and increased bone marrow activity (where red blood cell production occurs) can decrease bone marrow density, weaken bones, and increase your risk of fractures.
• Heart problems: Excess iron buildup from regular blood transfusions can lead to heart problems, including arrhythmias (abnormal heartbeat), heart attack, or congestive heart failure.
• Endocrine disorders: Beta thalassemia major can affect the function of the pituitary and thyroid glands, leading to hormonal imbalances, growth delays, and hypothyroidism.
  

People with beta thalassemia also have an increased risk of other health problems, such as:

• Blood clots 
• Dementia 
• Gallstones 
• Leg ulcers due to reduced oxygen supply to the skin 
• Low back pain 
• Leg pain 
• Nutrient deficiencies

Living With Beta Thalassemia 

Living with beta thalassemia requires proactive management, which includes following your treatment plan and making certain lifestyle adjustments based on your symptoms and treatment schedule. For people with beta thalassemia major, frequent blood transfusions are a part of life, and many people report that the significant time investment can be a burden and interfere with daily activities and quality of life.

Recent research advancements have led to the development of new treatments that may reduce the amount of blood transfusions you need; talk to your healthcare provider to discuss whether these options are a good fit.

Managing beta thalassemia is a lifelong journey, but it doesn't have to define your life. By focusing on what is within your control, advocating for your needs, and leaning on friends and family for support, it is possible to navigate the challenges and enjoy a fulfilling life.