Thalassaemia

Thalassaemia is an inherited blood disorder that disrupts the body’s ability to produce healthy haemoglobin, causing red blood cells to form incorrectly and leading to anemia that ranges from mild to life-threatening.

Table of contents

• What is thalassaemia?
• What causes thalassaemia?
• Who is at risk?
• Types of thalassaemia
• Symptoms
• Diagnosis
• Treatment
• Living with thalassaemia

What is thalassaemia?

Thalassaemia is an inherited blood disorder that affects your body’s ability to produce normal haemoglobin (a protein in red blood cells that carries oxygen throughout your body)^[1]. When you have thalassaemia, your body produces fewer healthy haemoglobin proteins, and your bone marrow produces fewer healthy red blood cells^[1].

The condition of having fewer red blood cells is called anemia^[1]. As red blood cells serve the vital role of delivering oxygen to tissues in your body, not having enough healthy red blood cells can deprive your body’s cells of the oxygen they need to make energy and thrive^[1].

What causes thalassaemia?

Thalassaemia is caused by faulty genes that affect the production of haemoglobin^[6]. Haemoglobin consists of four protein chains: two alpha globin chains and two beta globin chains. Each chain contains genetic information, or genes, passed down from your parents^[1].

Alpha globin protein chains consist of four genes, two from each parent. Beta globin protein chains consist of two genes, one from each parent^[1]. If any of these genes are defective or missing, you will have thalassaemia. The thalassaemia you have depends on whether your alpha or beta chain contains the genetic defect^[1].

A child can only be born with thalassaemia if they inherit these faulty genes from both parents^[6]. For example, if both parents have the faulty gene that causes beta thalassaemia major, there’s a 1 in 4 chance of each child they have being born with the condition^[6].

Who is at risk?

The gene mutations that cause thalassaemia arose in humanity as partial protections against malaria^[1]. As a result, thalassaemia affects people who have ancestral links to parts of the world where malaria is prevalent, such as Africa, Southern Europe and West, South and East Asia^[1].

It mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin^[6]. Alpha thalassemias occur most often in people from Southeast Asia, the Middle East, China, and in those of African descent^[5]. Beta thalassemias occur most often in people of Mediterranean origin. To a lesser extent, Chinese, other Asians, and African Americans can be affected^[5].

Types of thalassaemia

When we talk about different types of thalassaemia, we might be talking about one of two things: the specific part of haemoglobin that is affected (usually either alpha or beta), or the severity of thalassaemia, which is noted by words like trait, carrier, minor, intermedia, or major^[3].

Thalassaemia is classified as trait, minor, intermedia and major to describe how severe the condition is. Having a thalassaemia trait means that you may experience mild anemia symptoms or no symptoms at all and may not need treatment. Thalassaemia major is the most serious form and usually requires regular treatment^[1].

Alpha thalassaemia

You inherit four genes, two from each parent, that make alpha globin protein chains. When one or more genes are defective, you develop alpha thalassaemia^[1]. The number of defective genes you inherit will determine whether you experience anemia symptoms and how severe they will be.

One defective or missing alpha gene means that you won’t experience symptoms. Another name for this condition is alpha thalassaemia minima^[1]. Two defective or missing alpha genes means that if you experience symptoms, they’ll likely be mild. Another name is alpha thalassaemia minor^[1].

Three defective or missing alpha genes means that you’ll experience moderate to severe symptoms. Another name for this condition is Haemoglobin H disease^[1]. Four defective or missing alpha genes usually results in death^[1]. The most severe form of alpha thalassaemia major causes stillbirth^[5].

Beta thalassaemia

Beta thalassaemia occurs when similar gene defects affect production of the beta globin protein^[5]. Beta thalassaemia major is also called Cooley anemia^[5].

A heterozygous mutation (beta-plus thalassaemia) results in beta-thalassaemia minor in which beta chains are underproduced. It is mild and usually without symptoms^[4]. Beta thalassaemia major is caused by a homozygous mutation (beta-zero thalassaemia) of the beta-globin gene, resulting in the total absence of beta chains. It manifests clinically as jaundice, growth retardation, enlarged spleen and liver, endocrine abnormalities, and severe anemia requiring life-long blood transfusions^[4].

Children born with beta thalassaemia major are normal at birth, but develop severe anemia during the first year of life^[5]. The condition in between these two types is called beta-thalassaemia intermedia with mild to moderate clinical symptoms^[4].

Thalassaemia trait (carriers)

A carrier of thalassaemia is someone who carries at least 1 of the faulty genes that causes thalassaemia, but does not have thalassaemia themselves. It’s also known as having the thalassaemia trait^[6].

If you’re a thalassaemia carrier, you will not develop thalassaemia. Being a carrier will not generally cause you any health problems. But you may get mild anemia because your red blood cells are smaller than usual and your haemoglobin level may be slightly lower than normal^[6]. If you’re a thalassaemia carrier, you’re at risk of having children with thalassaemia^[6].

Symptoms

The symptoms that you have depend on the type of thalassaemia and how serious it is^[2]. Most people born with thalassaemia experience health problems from a few months after birth. Less severe cases may not be noticeable until later in childhood or even until adulthood^[6].

Since your body has fewer red blood cells when you have thalassaemia, you may have symptoms of a low blood count, or anemia^[3]. When you have anemia, you might feel tired or weak. Symptoms of anemia include tiredness, weakness, feeling cold, dizziness, and pale skin^[1].

Symptoms of severe thalassaemia can include tiredness (also called fatigue), weakness, a change in skin color or a yellowing of skin and eyes, changes or problems with facial bones, slow growth, swelling of the stomach area (also called the abdomen), dark urine, and poor appetite^[2]. You might also experience shortness of breath, a fast heart beat, headache, leg cramps, difficulty concentrating, and pale skin^[3].

Other symptoms can include bone deformities in the face and growth failure^[5]. People with the minor form of alpha and beta thalassaemia have small red blood cells but no symptoms^[5].

Diagnosis

Thalassaemia is often detected during pregnancy or soon after birth^[6]. Screening for thalassaemia in pregnancy is offered to all pregnant women in England to check if there’s a risk of a child being born with the condition, and some types may be picked up during the newborn blood spot test (heel prick test)^[6].

Blood tests can also be carried out at any age to check for thalassaemia or to see if you’re a carrier of a faulty gene that causes it^[6]. Your health care provider will do a physical exam to look for an enlarged spleen^[5].

A blood sample will be sent to a laboratory to be tested. Red blood cells will appear small and abnormally shaped when looked at under a microscope^[5]. A complete blood count reveals anemia^[5]. A test called haemoglobin electrophoresis shows the presence of an abnormal form of haemoglobin and can detect beta thalassaemia^[5]. A test called mutational analysis can help detect alpha thalassaemia^[5].

Prenatal testing

Testing can be done before a baby is born to find out if the baby has thalassaemia and determine how serious the condition might be^[10]. Tests used to find thalassaemia in unborn babies include chorionic villus sampling and amniocentesis^[10].

Chorionic villus sampling involves removing a tiny piece of the placenta, which is then checked by a lab. Most often, it’s done around the 11th week of pregnancy^[10]. Amniocentesis involves checking a sample of the fluid that surrounds the unborn baby in the womb. The test usually is done around the 16th week of pregnancy^[10].

Treatment

Treatments for thalassaemia depend on the type and how serious it is^[12]. If you are a carrier or have alpha or beta thalassaemia trait, you likely have mild or no symptoms and may not need treatment^[11]. Mild forms of thalassaemia trait don’t need treatment^[10].

Blood transfusions

Blood transfusions are the main way to treat moderate or severe thalassaemia^[11]. This treatment gives you red blood cells with healthy haemoglobin. During a blood transfusion, a needle is used to insert an intravenous line into one of your blood vessels. You receive healthy blood through this line. The procedure usually takes 1 to 4 hours^[11].

How often blood transfusions are needed depends on how serious your condition and symptoms are^[11]. Occasional blood transfusions may be needed for people who have haemoglobin H disease or beta thalassaemia intermedia. Regular blood transfusions (every 3 to 4 weeks) may be needed for people who have beta thalassaemia major^[11]. People with the most severe type, beta thalassaemia major, may need a blood transfusion about once a month^[13].

Iron chelation therapy

The haemoglobin in red blood cells is an iron-rich protein. Regular blood transfusions can cause iron buildup, or iron overload, which can lead to potentially life-threatening complications^[11]. To prevent this, doctors use iron chelation therapy in people who receive regular blood transfusions to remove excess iron from the body^[11].

Treatment to remove excess iron caused by regular blood transfusions is known as chelation therapy. It’s very important because high levels of iron in the body can damage organs^[13]. Medicines used in chelation therapy are known as chelating agents^[13].

Three medicines are used for iron chelation therapy: desferrioxamine, given as an infusion; deferiprone, taken as a tablet or liquid 3 times a day; and deferasirox, taken once a day as a tablet that you swallow or dissolve in a drink^[13]. Each medicine has its own advantages and disadvantages. Your healthcare team will help you decide which is likely to be best for you or your child^[13].

Folic acid

Many times people with thalassaemia are prescribed a supplemental B vitamin, known as folic acid, to help treat anemia^[12]. Folic acid can help red blood cells develop. Treatment with folic acid is usually done in addition to other therapies^[12]. If you receive blood transfusions, you should not take iron supplements. Doing so can cause a high amount of iron to build up in the body, which can be harmful^[5].

Gene therapy

In January 2024, the U.S. Food and Drug Administration approved a cell-based gene therapy for the treatment of transfusion-dependent beta-thalassaemia in patients 12 years and older^[12]. The product is made from patients’ own blood stem cells. The stem cells are taken, modified, and given back as a one-time, single-dose infusion as part of a blood stem cell transplant^[12].

Stem cell or bone marrow transplants

Stem cell or bone marrow transplants are the only cure for thalassaemia, but they’re not done very often because of the significant risks involved^[13]. Stem cells are produced in bone marrow, the spongy tissue found in the centre of some bones, and have the ability to develop into different types of blood cells^[13].

For a stem cell transplant, stem cells from a healthy donor are given through a drip into a vein. These cells then start to produce healthy red blood cells to replace the cells affected by thalassaemia^[13]. A stem cell transplant is an intensive treatment that carries a number of risks. The main risk is graft versus host disease, which is a life-threatening problem where the transplanted cells start to attack the other cells in your body^[13].

Other treatments

Thalassaemia can also cause a number of other health problems that may need to be treated. For example, hormone medicine may be used to help trigger puberty in children with delayed puberty and treat low hormone levels. Vaccinations and antibiotics may be recommended to prevent and treat infections^[13]. Thyroid hormones may be used if there’s a problem with your thyroid gland, and medicines called bisphosphonates may be used to help strengthen your bones^[13].

Living with thalassaemia

For people with thalassaemia, a healthy lifestyle means managing the disorder and making healthy choices^[17]. If a doctor has prescribed either blood transfusions or chelation therapy, the most important thing a person with thalassaemia can do is stick to their transfusion and chelation schedules to prevent severe anemia and possible organ damage from iron overload^[17].

There are a number of things you can do to help you stay as healthy as possible if you have thalassaemia. To help reduce your chances of developing some of the problems associated with thalassaemia, it’s a good idea to have a healthy, balanced diet, exercise regularly, avoid smoking and drinking excessive amounts of alcohol, and try to avoid infection^[18].

Vaccinations

Vaccines are a great way to prevent many serious infections^[17]. Children and adults with thalassaemia should get all recommended vaccinations, including a flu vaccination. People with thalassaemia are considered “high risk” for certain infections, especially if they have had their spleen removed^[17]. Getting recommended vaccines is important, especially if you have had your spleen removed. These include routine vaccines for pneumococcus, hepatitis B, meningitis, and COVID-19, as well as a flu shot every year at the start of flu season^[22].

Nutrition

Eating nutritious foods is important for everyone to maintain a healthy lifestyle. A diet, high in fruits and vegetables and low in fats is ideal for gaining the essential nutrients our bodies need^[17]. For people living with thalassaemia, because too much iron may build up in the blood, foods high in iron may need to be limited. Iron can be found in meat, fish, and some vegetables (like spinach)^[17].

You do not usually need a special diet, although sometimes you may be advised to take supplements such as folic acid, calcium or vitamin D^[18]. Persons with thalassaemia should discuss with their doctor whether or not they should limit the amount of iron in their diet^[17].

Exercise

Exercise is part of an overall healthy lifestyle and helps lead to better health outcomes^[17]. Regular exercise, particularly weight-bearing and aerobic exercise, can help strengthen bones and reduce the risk of osteoporosis^[18]. Although some people with thalassaemia may have trouble participating in vigorous forms of exercise, many people with thalassaemia can participate in moderate physical activities including biking, running, and walking^[17]. If you have thalassaemia, you should discuss with your doctor the level of exercise that would be best for you^[17].

Outlook

Although the main health problems associated with thalassaemia can often be managed with treatment, it’s still a serious health condition that can have a significant impact on a person’s life^[6]. Without close monitoring and regular treatment, the most severe types can cause serious organ damage and be life threatening^[6].

In the past, severe thalassaemia was often fatal by early adulthood. But with current treatments, people are likely to live into their 50s, 60s and beyond^[6]. Severe thalassaemia can cause early death (between ages 20 and 30) due to heart failure if untreated. Getting regular blood transfusions and therapy to remove iron from the body helps improve the outcome^[5].

Less severe forms of thalassaemia often do not shorten lifespan^[5]. You may want to seek genetic counselling if you have a family history of the condition and are thinking of having children^[5].