Thalassemia: Understanding This Inherited Blood Disorder

Thalassemia is a group of blood disorders in which the body doesn't make enough hemoglobin, the protein that carries oxygen in red blood cells. In thalassemia, red blood cells don't function as well or last as long as they should. This shortage of healthy red blood cells means some cells in the body can't get enough oxygen.

People with thalassemia may develop mild to severe anemia. Anemia is when you don't have enough healthy red blood cells. Mild anemia can cause symptoms such as fatigue and shortness of breath but doesn't always require treatment. Severe anemia can lead to serious organ damage. Treatment may include regular blood transfusions.

Thalassemia usually is an inherited condition, but in some instances, it can be acquired, usually in a person with a type of blood cancer. This article explains thalassemia, including the types, causes, symptoms, diagnosis, treatment, and outlook.

What Does Thalassemia Do to a Person?

Thalassemia is a serious disease that can have a huge impact on your life. Even if you have a mild case, you'll always want to monitor the condition. It can be managed, and many people with thalassemia live long, healthy lives. More severe cases require lifelong treatment and can lead to serious complications.

Thalassemia

Thalassemia Types

The two main types of thalassemia are alpha and beta, based on which part of the hemoglobin protein isn't being made.

Alpha-Thalassemia

Alpha-thalassemia is related to changes or deletions in genes that make a protein subunit of hemoglobin called alpha-globin. This involves two adjacent genes (HBA1 and HBA2) on one chromosome. You inherit two of these genes from each parent since you get one chromosome from each parent (a total of four genes).

This can result in these types of thalassemia:

• Alpha-thalassemia minor (trait): Involves two gene deletions and causes mild or no symptoms
• Alpha-thalassemia intermedia (deletional HbH disease): Involves three gene deletions and mild to moderate symptoms
• Non-deletional HbH disease (constant spring): Involves reduced alpha-globin activity and severe symptoms
• Alpha-thalassemia major (Hb Bart’s hydrops fetalis): Involves four gene deletions and severe symptoms that can be fatal during gestation or shortly after birth

While usually an inherited condition, alpha-thalassemia can also develop secondary to a cancer of the blood-forming cells. In most cases, this occurs in a person with myelodysplastic syndrome.

Beta-Thalassemia

Beta-thalassemia involves changes (mutations) of the HBB gene that makes a protein subunit of hemoglobin called beta-globin. You inherit one of these genes from each parent. This can result in these types:

• Beta-thalassemia minor (trait): Involves one faulty gene and causes mild symptoms or none at all
• Beta-thalassemia intermedia: Involves two faulty genes and causes mild to moderate symptoms
• Beta-thalassemia major (Cooley's anemia): Involves two faulty genes and causes severe symptoms
• Dominant beta-thalassemia: A very rare type that involves one faulty gene and causes mild to moderate symptoms

Beta thalassemia can extremely rarely occur as an acquired, non-inherited condition, usually in a person with myelodysplastic syndrome.

Thalassemia Causes and Risk Factors

Thalassemia happens when you inherit certain gene mutations or gene deletions. Alpha-thalassemia usually involves mutations in the HBA1 and HBA2 genes, but there are rare syndromes involving other genes. Beta-thalassemia is usually the result of a mutation in the HBB gene.

Except in rare instances, if you inherit these gene mutations from only one parent, you'll be a silent carrier and won't develop thalassemia. When both parents are carriers, the children have a 25% chance of inheriting two trait genes and developing the disease. They have a 50% chance of being a trait carrier. Thalassemia is most common in people whose ancestry is:

• Italian
• Greek
• Middle Eastern
• Southern Asian
• African

Acquired alpha-thalassemia or beta-thalassemia are rare and usually seen when a person has a type of blood cancer. The cancerous cells have undergone non-inherited genetic changes that result in thalassemia.

Thalassemia Symptoms

Symptoms vary according to type and severity. Anemia causes most signs and symptoms associated with thalassemia, including:

• Tiredness
• Weakness
• Shortness of breath
• Fast heartbeat
• Pale skin
• Dizziness, fainting
• Headaches
• Trouble concentrating
• Leg cramps

Children with severe types of thalassemia may have:

• Pale skin
• Jaundice (yellowing of the skin and whites of the eyes)
• Enlarged spleen or liver
• Dark urine
• Loss of appetite
• Intellectual or developmental disabilities
• Changes to facial bones

Most people with thalassemia have health problems within a few months of birth. In mild cases, symptoms may not be apparent until later in childhood or adulthood.

How Thalassemia Is Diagnosed

If your provider suspects thalassemia, they'll likely ask about your family's medical history. Diagnostic testing may include:

• Complete blood count (CBC): To measure different components of blood and blood cells
• Hemoglobin electrophoresis: To detect different types of hemoglobin
• Ferritin test: To measure iron in the blood
• Molecular genetic testing: To detect gene mutations and confirm the diagnosis

Newborn screening tests check for many blood abnormalities, including beta-thalassemia.

If you're pregnant and think your fetus may be at risk of thalassemia, ask your healthcare provider about prenatal testing such as:

• Chorionic villus sampling (CVS): Involves taking a sample of tissue from the placenta at 10 to 13 weeks gestation
• Amniocentesis: Involves taking an amniotic fluid sample at 15 to 20 weeks gestation
• Ultrasound: A noninvasive procedure that helps providers see how blood flows through cerebral arteries, usually at 13 to 14 weeks gestation
  

Thalassemia Treatment and Home Care

Treatment depends on the type and severity. If you're a carrier, you don't need treatment. People with alpha- or beta-thalassemia traits have mild to no symptoms and may not need treatment.

Blood transfusions are the main treatment for moderate to severe thalassemia. In this procedure, you get healthy red blood cells through an intravenous (IV) line, which can take several hours.

How often you need a transfusion depends on the severity of the disease and your desired hemoglobin levels. A transfusion every three to four weeks may be necessary for people with beta-thalassemia major.

Blood transfusions can leave your blood with too much iron. Iron chelation therapy helps remove the excess to avoid complications. Drugs used for iron chelation include Exjade or Jadenu (deferasirox) and Ferriprox (deferiprone), which are available in pill form. Deferoxamine is given by infusion in a hospital or subcutaneously (just under the skin) at home using a pump overnight.

A stem cell transplant is a potential cure for thalassemia, but finding a good match is rare. In this procedure, healthy blood cell precursors (stem cells) are harvested from a compatible donor. The recipient's bone marrow is treated to eliminate their stem cells. The donor cells are infused into the recipient. They migrate to the bone marrow and establish new production of healthy blood cells.

Other treatments can include:

• Reblozyl (luspatercept-aamt): May lower the number of blood transfusions you need
• Hydroxyurea: To lower the risk of complications
• Splenectomy: Surgical removal of the spleen
  

Self-care measures should include:

• Maintain a nutritious diet. Ask your provider how much iron is right for you.
• Get regular physical activity. Discuss your exercise routine with your provider if you have osteoporosis (progressive bone thinning).
• Avoid smoking or excessive drinking, as these can affect bone and heart health.
• Try to avoid getting infections (and stay up-to-date with vaccinations).
• Take medicines as directed and tell your provider about all dietary supplements.

Possible Complications

Thalassemia makes your body work harder to make red blood cells. This can lead to complications such as:

• Osteoporosis: Most red blood cells are made in the bone marrow. Extra effort to make red blood cells can cause stretching and thinning of the bones, which can make fractures more likely.
• Enlarged spleen: The spleen breaks down old or disordered red blood cells. The additional workload in thalassemia can cause the spleen to enlarge, and it can't filter blood or fight infection as well as it should. People with thalassemia are immunocompromised and at higher risk of infection and disease.

Other potential complications include:

• Iron overload (due to frequent blood transfusions)
• Problems with the heart, liver, thyroid, and gallbladder
• Leg ulcers, blood clots
  

Can You Prevent Thalassemia?

In cases of inherited thalassemia, there's really no way to prevent it. But you might consider testing for thalassemia if a family member has it. You can also speak with a genetic counselor to assess the risk of passing it on to your children.

Thalassemia Outlook and Life Expectancy

Thalassemia can often be managed. People with mild thalassemia generally have a normal life expectancy.

Life expectancy for severe types has improved a lot over the past half century. This may be due, in part, to early detection, transfusions, and chelation therapy. Heart disease is the most common cause of death associated with thalassemia.

With proper treatment, many people with severe thalassemia are likely to live into their 50s, 60s, and beyond.

When to See a Healthcare Provider

See a healthcare provider if you or your child have any signs or symptoms of thalassemia. Also, consider meeting with a genetic counselor if you have a family history of the disease.

Summary

Thalassemia is a blood disorder in which your body doesn't make enough healthy hemoglobin. That leads to a shortage of healthy red blood cells, known as anemia. Symptoms can range from mild to life-threatening.

Many people with mild thalassemia live a normal, healthy life span. Treatment for more serious cases usually involves periodic blood transfusions and iron chelation therapy.

Thalassemia is an inherited condition, so there's no way to prevent it. Symptoms usually appear early in childhood. Early treatment is crucial, so see a healthcare provider if your child has symptoms.