Thalassemia

What Is Thalassemia?

Thalassemia is an inherited, lifelong disorder that affects the development and health of red blood cells, which transport oxygen. Lack of healthy red blood cells can cause a range of problems. Without treatment, more severe forms of thalassemia can restrict daily activities and even threaten your life.

Thalassemia results in problems with hemoglobin, the protein that carries oxygen for red blood cells. During the formation of new red blood cells in the bone marrow, hemoglobin develops from a careful linking of two distinct building blocks. At a certain point, the completed hemoglobin joins the maturing red blood cells.

With thalassemia, an inherited genetic change disrupts this crucial process. The change reduces production of one of the hemoglobin building blocks. Which building block is affected depends on the genes involved.

Without enough fully formed hemoglobin, the developing red blood cells die. Also, without proper partners, the other set of hemoglobin building blocks attaches to mature red blood cells and damages them, shortening their lives.

The subsequent impacts on red blood cell production and health include:

• Anemia, or a shortage of healthy red blood cells
• Arrhythmias (irregular heartbeats), heart failure, and pulmonary hypertension over time, with the heart and lungs working harder
• Bone marrow expansion as it attempts to make up for red blood cell loss, resulting in bone deformities, bone weakening, and fractures
• Damage to organs from lack of oxygen
• Gallstones, as dying red blood cells release a substance called bilirubin that collects in the gallbladder
• Hypercoagulability, or an increased tendency to form blood clots
• Leg ulcers
• Poor growth in children and failure to thrive in adults
• Production of red blood cells outside the bone marrow, including in the spleen, which can then enlarge

Thankfully, improvements in care have led to better control of thalassemia and its potential complications. Many people with the condition now enjoy longer, fuller lives. To take advantage of these advances, people with more severe forms of thalassemia may wish to receive focused care.

At Penn Medicine, adults seeking specialized thalassemia services can turn to our Comprehensive Adult Thalassemia Program.

Thalassemia Symptoms

Some types of thalassemia can lead to severe complications, while other forms only cause mild or moderate symptoms. People with thalassemia may also have different (or worse) symptoms and complications as they get older.

Broadly speaking, thalassemia symptoms vary depending on the type of complication involved. With anemia, one of the more frequent complications, symptoms can include:

• Fatigue
• Pale skin
• Shortness of breath
• Weakness

The type of anemia caused by thalassemia can also lead the body to absorb more iron from food. This iron buildup can cause problems with certain organs and glands and possibly worsen the side effects of treatment.

Types of Thalassemia

Thalassemia has two main types, defined by which of the hemoglobin building blocks it affects. These types are further broken into subtypes, based on how they are inherited and how they affect the body.

Alpha Thalassemia

Alpha thalassemia is caused by changes to the two genes responsible for making the hemoglobin building block called alpha-globin.

People normally inherit four total copies of these alpha-globin genes — two copies from each parent. The type of alpha thalassemia and its severity depend on how many gene copies are affected and in what way. The more alpha-globin genes missing, the more severe the disease.

Subtypes of alpha thalassemia include:

• Silent carriers: People with one affected gene copy are said to be “silent” carriers. They generally have no symptoms and do not need any treatment. Silent carriers can still pass the thalassemia genetic changes to their children.
• Alpha thalassemia trait: People with two affected gene copies have what’s known as alpha thalassemia trait. They may have mild anemia but are generally asymptomatic and do not need therapy. They can, however, pass on the genetic changes to their children. We recommend that people of childbearing age with alpha thalassemia trait ask their partners to get tested and receive genetic counseling. These steps can help determine the risk of having a more severely affected child.
• Hemoglobin H (HbH) disease: Three deleted gene copies can cause a significant reduction in alpha-globin. An unusual type of hemoglobin called hemoglobin H then develops. People may end up with mild to moderate symptoms and, in some cases, may require blood transfusions.
• Alpha thalassemia major: This subtype develops when all four gene copies are involved. Alpha thalassemia causes severe, life-threatening complications during fetal development. Thankfully, recent treatment advances have allowed doctors to start blood transfusions in the womb. This innovation has allowed newborns to survive and begin lifelong treatment. It’s important to identify couples at risk for alpha thalassemia major. Early identification allows for genetic counselling, early fetal screening, and treatment in the womb.

Alpha thalassemia is found most often in families of Southeast Asian descent. The condition is also found in families descending from South Asia, Central Asia, the Middle East, and Africa.

Beta Thalassemia

Beta thalassemia comes from changes in the gene responsible for making beta-globin, the other hemoglobin component.

Some of these genetic changes lead to no beta-globin production (beta-zero thalassemia). With others, a moderate amount of beta-globin is produced (beta-plus thalassemia). This difference may affect disease severity, but not always.

Each person has two beta-globin gene copies — one from each parent. Sometimes, people carry some of the genetic changes responsible for beta thalassemia but have few or no symptoms. They only pass on more severe forms if they have a child with someone else who also has genetic changes tied to beta thalassemia.

Scenarios for inheriting beta thalassemia include:

• Beta thalassemia minor (beta thalassemia trait): In this situation, an individual inherits one changed gene copy from one parent. These individuals generally do not have symptoms and have normal growth and development. No treatment is generally needed.
• Beta thalassemia intermedia: This version occurs when someone inherits one changed gene copy from each parent. The symptoms and complications vary depending on the severity of the changes. They may range from mild cases not needing blood transfusions to more severe forms in which transfusions help prevent complications and allow the individual to thrive.
• Beta thalassemia major: While this version also involves changes to both gene copies, it results in a more severe deficiency or complete absence of beta-globin. It also causes more severe symptoms, often affecting the children at a young age. A long-term treatment plan with regular red blood cell transfusions is key for beta thalassemia. However, these transfusions also lead to iron overload and other organ complications. These side effects require regular checkups, iron load monitoring, and specialized treatments such as chelation therapy.

Beta thalassemia is found in families descending from the Mediterranean, the Middle East, Africa, Southeast Asia, and southern China.

How Is Thalassemia Diagnosed?

Doctors diagnose thalassemia with blood tests that look at the number of red blood cells, their shape, and their size. The tests also evaluate hemoglobin subtypes. Genetic testing may be able to determine the changes responsible, though results may not alter the treatment approach.

Since at-risk couples can be identified, thalassemia major may be diagnosed early in pregnancy. Otherwise, children with moderate or severe symptoms typically get diagnosed early in life.

With mild thalassemia, people may not learn they have it until adulthood. They may get a blood test for another reason or need care for anemia.

Thalassemia Treatment

Thalassemia treatment depends on the type you have and how it affects you. Some people only need occasional treatment, if any. Others require ongoing therapy.

Standard thalassemia treatment involves transfusions of donated red blood cells, which are screened for safety. These transfusions help relieve anemia and other symptoms. They also slow the bone marrow’s unsuccessful attempts at continued red blood cell production.

Additional thalassemia treatments may help the body produce and maintain healthy red blood cells. These treatments may include hydroxyurea and luspatercept.

Researchers have also been developing ways to add the genetic information needed to make proper hemoglobin to the body. The Food and Drug Administration approved the first gene therapy for thalassemia in 2022. Doctors hope this one-time treatment will make people less dependent on blood transfusions or not need them at all.

Treatment Side Effects and Chelation Therapy

While blood transfusions provide critical treatment for thalassemia, they also further contribute to the harmful buildup of iron. This process occurs when the donated red blood cells reach their normal lifespan and break apart, releasing iron.

The excess iron tied to thalassemia-related anemia and blood transfusions can cause problems as it collects in certain parts of the body:

• Bones: Extra iron can combine with other thalassemia-related changes to cause osteoporosis.
• Endocrine system: The extra iron can lead to disorders such as diabetes and hyperthyroidism.
• Heart: The deposits can cause arrhythmias and heart failure.
• Liver: The iron can cause scarring that can eventually turn into cirrhosis. It can also raise the risk for liver cancer.

To prevent iron from building up, doctors use special medications called chelators to remove some of the mineral from the body. They also give these medications when iron has already collected. Fortunately, advances in chelation therapy have made iron removal easier and much more effective.

Additionally, doctors watch for the side effects of iron buildup during regular checkups. They sample blood, test organs and glands, and use imaging to identify possible complications.

Make an Appointment

Please call 800-789-7366 or make an appointment.

Penn Programs & Services for Thalassemia