Thalassemia | Symptoms & Causes
What are the symptoms of thalassemia?
Symptoms of thalassemia depend on the severity of the disease and how it is treated. Each child may experience symptoms differently. Patients with thalassemia trait generally do not experience any symptoms.
Transfusion-dependent thalassemia (TDT)
The main signs and symptoms of TDT in infancy, before diagnosis and treatment, are severe anemia as well as symptoms caused by overproduction of immature, defective red blood cells. This overproduction can weaken the bones, leading to fractures and facial deformity, and cause enlargement of the spleen and liver.
Patients with TDT do not typically experience severe anemia once they have started receiving regular transfusions. Without these transfusions, however, they can develop life-threatening anemia.
Later in childhood and adulthood, TDT symptoms are generally the result of iron overload, a byproduct of the frequent blood transfusions patients require. Symptoms of iron overload may include:
- chronic fatigue
- liver disease
- abdominal pain
- heart problems
- joint pain
Non-transfusion-dependent thalassemia (NTDT)
In general, children with non-transfusion-dependent thalassemia experience less severe symptoms. They need regular medical follow-up, but may not require frequent blood transfusions until later in life. The most common symptoms of NTDT are related to anemia and overproduction of immature, defective red blood cells. To avoid these symptoms, a transfusion regimen is often recommended.
Symptoms may include:
- pale skin, lips, hands, or paleness under the eyelids
- increased heart rate (tachycardia)
- breathlessness or difficulty catching a breath (dyspnea)
- lack of energy or tiring easily (fatigue)
- dizziness or vertigo, especially upon standing
- headache
- irritability
- irregular menstrual cycles
- absent or delayed menstruation (amenorrhea)
- slow or delayed growth and development
- bony overgrowth or deformities
- an increased risk of bone fractures
- enlargement of the spleen or liver
What causes thalassemia?
Thalassemia is caused by an abnormality or mutation in DNA that affects the genes responsible for hemoglobin production. Hemoglobin is made up of four parts: two alpha-globin proteins and two beta-globin proteins. Thalassemia is caused by abnormalities in one or more of the genes that produce these proteins.
Children inherit thalassemia from their parents. When one parent is a carrier for thalassemia, a child may develop a mild form of the condition called thalassemia minor, also called “thalassemia trait.” When both parents are carriers of thalassemia, there is a greater chance their child or children will inherit a more serious form of the condition.
Thalassemia | Diagnosis & Treatments
How is thalassemia diagnosed?
A diagnosis of thalassemia is made after tests to discover which type of thalassemia a child might have. Those tests include:
- a complete blood count (CBC) to measure the number of red blood cells and their concentration of hemoglobin, as well as many other red cell features
- hemoglobin electrophoresis, which measures the amount and type of hemoglobin in the blood
- genetic tests to identify specific genetic defects that cause thalassemia
- In some cases, special testing, including chorionic villus sampling and amniocentesis, can be done before birth to determine if a baby has thalassemia and how severe the condition is
What are the treatment options for thalassemia?
Once thalassemia is diagnosed in a child, treatment may involve many specialists, including specialists in hematology and transfusion medicine as well as cardiologists, endocrinologists, gastroenterologists, nephrologists, audiologists, ophthalmologists, infectious disease specialists, geneticists, and genetic counselors as necessary.
Treatment for thalassemia depends on its severity. If your child has transfusion-dependent thalassemia (TDT), they will require life-long, ongoing medical care, which may include:
- medications and supplements to counteract anemia, including luspatercept (Reblozyl), a novel therapy for anemia in TDT
- medications such as hydroxyurea, which can stimulate the production of fetal hemoglobin
- blood transfusions from healthy donors to alleviate anemia. How often a child will need transfusions will depend on the type of thalassemia.
- monitoring for iron overload in children receiving regular transfusions to prevent complications (iron overload can cause organ damage.) We use specialized magnetic resonance imaging (MRI) technologies to measure the degree of iron overload.
- iron chelation therapy, which reduces the amount of iron in the body and prevents or treats iron overload. Treatments we use include oral deferasirox (Jadenu or Exjade), oral deferiprone (Ferriprox), and intravenous or subcutaneous deferoxamine (Desferal).
- stem cell transplantation to replace the defective blood-forming stem cells with healthy stem cells from a donor. This treatment can cure thalassemia, but it may not be an option for everyone. Success depends on many factors, such as the child’s age, health of their bone marrow, and how close the match is between child and donor (matched siblings are best; if your child has a sibling, there is a 1 in 4 chance they will be a match). The decision of whether to proceed with a stem cell transplant should be discussed with your child’s hematologist and a stem cell transplant team.
Gene therapy for transfusion-dependent beta thalassemia (Zynteglo® and Casgevy™)
Two FDA-approved gene therapies are now available at Boston Children’s for patients with beta thalassemia who require regular transfusions of red blood cells. Both treatments involve collecting blood-forming stem cells from the patient’s blood and manipulating them genetically in a specialized lab. However, the cells are treated in different ways.
- Zynteglo®, also called beti-cel, was approved in August 2022 for eligible children and adults. It uses a self-inactivating lentivirus to deliver a functioning copy of the beta-globin gene into patients’ blood stem cells. The cells then produce the beta globin gene and normal red blood cells.
- Casgevy™, also called exa-cel, was approved in January 2024 for patients aged 12 and older. It uses CRISPR editing of the BCL11A gene — a technology developed at Boston Children’s — to increase production of the fetal form of hemoglobin. This has been shown to reduce or eliminate the need for red blood cell transfusions.
Before receiving their genetically modified cells, patients receive several days of chemotherapy to eliminate the disease-causing stem cells in their bone marrow and allow room for the new stem cells to grow. The treated stem cells are then infused intravenously, similar to a standard blood transfusion.
Boston Children’s has extensive experience with gene therapies. To inquire or to refer a patient, email gene.therapy@childrens.harvard.edu.
What’s the long-term outlook for children with thalassemia?
In the past, children with transfusion-dependent thalassemia had a significantly reduced life expectancy. Today, however, thanks to blood transfusion therapy and effective iron chelators, the life expectancy for children with severe thalassemia is constantly improving. Survival to older adulthood was once rare but should now be expected. With a gene therapy now available, fewer patients may need to have frequent transfusions.
