What is thalassemia?
Thalassemia is an umbrella term for a group of genetic disorders affecting the body’s red blood cells.
People with thalassemia do not produce enough hemoglobin, an iron-rich protein within red blood cells that helps circulate oxygen throughout the body. A lack of hemoglobin can lead to symptoms of anemia such as fatigue and shortness of breath. People with thalassemia may also develop other health problems, such as slow growth, facial bone deformities, and an enlarged spleen, liver or heart.
Normal hemoglobin has four protein chains, two known as alpha globin and two known as beta globin. The two main types of thalassemia, alpha and beta, are named after hereditary defects in these protein chains. Each of these types has further subtypes, which are described in more detail later in the document.
Depending on which part of the hemoglobin protein is affected, thalassemia can vary from a mild condition to a serious or life-threatening condition that requires long-term treatment and management.
Thalassemia is not caused by any environmental factors and it is not possible to catch it. The disorder is most common in people of Mediterranean, South Asian, Southeast Asian and Middle Eastern origin.
The symptoms of thalassemia are wide ranging, and vary according to the type of thalassemia a person has.
Those with thalassemia trait, also known as thalassemia carriers, will usually have no symptoms, or possibly mild anemia.
Anemia refers to a lack of red blood cells or hemoglobin in the blood. It develops in almost everyone with thalassemia major and other serious types of the disorder. In severe cases, it can be life-threatening.
Anemia results in a lack of oxygen being available to the body. Typical symptoms include:
- Tiredness and lethargy
Excess iron levels
Most people with thalassemia major or other severe types of the disorder will be at risk for what is known as iron overload. This is a possible side-effect of repeated blood transfusions, a necessary part of treatment for people with severe thalassemia. However, it can also occur on its own.
Excessive levels of iron in the body can cause:
- Heart problems
- Hormone problems, including diabetes, thyroid, adrenal and pituitary disorders
- Liver cirrhosis
- Delayed puberty in children
Signs and symptoms of thalassemia in infants
As a genetic disorder, thalassemia is present from birth, but will generally not begin to cause symptoms immediately.
Children born with beta thalassemia major usually develop symptoms a few months after birth.
Less severe cases may not cause any noticeable symptoms until later in childhood, or sometimes until adulthood.
Early signs and symptoms that may indicate the presence of thalassemia in babies include:
- Fatigue, fussiness and irritability
- Shortness of breath
- Pale skin
- Yellow skin and eyes, known as jaundice
- Protruding abdomen
- Dark urine
- Facial bone deformities
- Slow growth
If you think you or your child may have thalassemia, try the Ada app for a free symptom assessment.
Genes contain the instructions needed to make proteins in the body. Genes come in pairs, with one set inherited from the mother and one set inherited from the father. For the hemoglobin protein, two normal genes – one from each parent – are required to make healthy beta chains.
If a person inherits two faulty beta thalassemia genes, that person will develop beta thalassemia major, also known as Cooley’s disease. Babies with this condition will often seem healthy at first, but usually develop symptoms of thalassemia within the first two years of life. It is typically a serious and lifelong condition, requiring long-term treatment and management.
If a person inherits only one faulty beta thalassemia gene they will have thalassemia trait and become a carrier of thalassemia disease. They will generally be healthy or sometimes have mild anemia. However, they are at risk of passing on more severe thalassemia to their children.
Thalassemia intermedia is used to describe the disorder that occurs when a person has inherited two faulty beta genes, but the faults are less severe than in beta thalassemia major. People with this condition usually have moderately severe anemia and sometimes require blood transfusions.
Four normal genes – two from each parent – are required to make healthy alpha chains, so alpha thalassemia involves four potentially faulty genes, rather than just two.
A person who inherits one or two faulty alpha genes will be a carrier, without symptoms, except sometimes slight anemia.
If they inherit three faulty alpha thalassemia genes, they will develop hemoglobin H disease, with moderate to severe symptoms.
With four faulty genes, alpha thalassemia major will occur, characterized by hydrops fetalis, in which excess fluid builds up in a baby’s body before birth, along with other physical abnormalities. Untreated alpha thalassemia major is almost always fatal, with a baby dying before delivery or shortly after birth. However, it can be diagnosed prenatally, and, if treatment is begun before the baby is born, they can survive. A specialist team will counsel the family about what treatment options may be suitable for their baby.
Women who are pregnant with babies that have inherited alpha thalassemia can also experience serious complications, including dangerously high blood pressure, premature delivery, and abnormal bleeding.
Thalassemia is normally diagnosed following blood tests. To make the diagnosis, a blood sample will be taken and analyzed in order to establish what type of hemoglobin is present. Occasionally, if the results prove inconclusive or there is any uncertainty, DNA tests may also be carried out.
Other conditions may present with similar symptoms, such as iron deficiency, vitamin B12 deficiency, erythropoietin deficiency, a bone marrow disorder called Diamond-Blackfan syndrome, and acute leukemia. It is important to identify the cause of a person’s symptoms, as each condition has different clinical consequences and treatment considerations. For instance, iron-deficiency anemia is usually treated with iron supplements, but it can be harmful for a person with thalassemia to take extra iron.
Moderate and severe thalassemias are usually diagnosed in early childhood, because the symptoms, such as severe anemia, will occur within the first few years of life.
Those who have milder forms might be diagnosed after a routine blood test shows anemia. A doctor may suspect thalassemia if a person is a member of an ethnic group that is at increased risk.
If you think you or your child may have thalassemia, try the Ada app for a free symptom assessment.
Prenatal thalassemia diagnosis
Blood tests can be carried out prior to conception to see whether a couple both have thalassemia trait, and if a future child could therefore inherit thalassemia.
It is also possible to find out if an unborn child is affected by thalassemia. This is usually done using tissue from the placenta, or amniotic fluid from the sac surrounding the embryo, and can be carried out from around 8 to 10 weeks into the course of a pregnancy.
Diagnosing thalassemia in newborn babies
If thalassemia is present, it will often be detected in a newborn baby as part of the routine postnatal screening process in many countries. A blood sample will be collected from a simple heel prick and sent to a laboratory for testing.
If the results return positive for thalassemia, the parents will have treatment options explained to them.
Postnatal tests will also be able to show whether or not a newborn has thalassemia trait. This is important, as it may increase the chances of a future sibling or the child’s future children inheriting the disorder.
A number of treatment methods are available to manage the symptoms of thalassemia and prevent complications. However, the disorder usually cannot be cured, and will require lifelong treatment in cases of thalassemia major or intermedia.
People with thalassemia major will be treated by a specialist and will be asked to attend check-ups at regular intervals.
Maintaining a healthy lifestyle is an important principle of managing thalassemia. This will typically involve:
Avoiding tobacco and excess alcohol to keep the bones and heart healthy
Regular exercise to help strengthen bones and reduce the risk of osteoporosis
Good nutrition and supplements to help prevent common deficiencies seen in people with thalassemia, such as taking folic acid to aid the body in its production of red blood cells, and calcium and vitamin D for bone health.
Thalassemia minor is often mistaken for iron-deficiency anemia and treated with iron supplements. However, people with anemia from thalassemia trait should not take iron supplements unless a blood test shows they have coexistent iron deficiency.
Besides these general principles above, there are two main treatments for thalassemia:
- blood transfusions
- chelation treatment
Blood transfusions are typically given to people with anemia accompanied by other complications, such as poor growth, enlarged spleen, evidence of heart disease, as well as in the case of pregnancy. Blood transfusions have associated risks and are only carried out when absolutely necessary, so those who have anemia without other symptoms may be advised against a transfusion.
Blood transfusions supply normal red blood cells to the affected person. This corrects the anemia temporarily, improving health and helping children to grow normally. However, the red blood cells have a limited lifespan, so the transfusion is normally repeated every three or four weeks.
People with moderate to severe thalassemia can experience iron building up to unhealthy levels in the body. This happens partly because of blood transfusions, but also because thalassemia causes the body to absorb more iron than normal from food. This can cause damage to internal organs and other potentially life-threatening complications.
Chelation treatment gets rid of excess iron from the body. Medication is given orally or via a drip. Once in the bloodstream, the chemical properties of the medication allow it to bind to excess iron. The medication and excess iron is then excreted from the body in urine or stools. Chelation therapy is usually begun within a year or two of beginning blood transfusions.
Stem cell transplants
A stem cell transplant is a possible cure for thalassemia, though there are risks of serious complications and even mortality. Stem cell transplants tend to have a better outcome in younger people. This therapy may be considered for a person who has a suitable donor.
A stem call transplant involves the administration of high-dose chemotherapy to eliminate thalassemia-producing cells in the bone marrow, and subsequent replacement with normal blood-making cells from a donor, resulting in a lifelong cure if successful.
There are various complications that can occur as a result of thalassemia. These include the following:
Growth and development problems
Children and adolescents with thalassemia may experience unusual bone growth as the bone marrow expands to try and make more blood cells, such as:
- An enlarged forehead or cheeks
- Thinning of the bones, known as osteoporosis
Puberty may be delayed or progress abnormally in teenagers with thalassemia, due to iron build up impairing the function of the pituitary gland. This may lead to complications such as:
- Absence of menstruation, known as amenorrhea
- Diminished functioning of the sex organs, known as hypogonadism
- Short stature
Doctors will monitor childhood development closely and may suggest hormone replacement therapy where necessary.
Anemia can cause the spleen to become enlarged, which, through various mechanisms, may actually make the anemia even worse. Some people with thalassemia will need to have an operation to remove their spleen. The spleen is a key part of the immune system and, if it is removed, a person will need immunizations and daily antibiotics to protect against certain infections such as pneumonia and meningitis.
Other possible complications include:
- Reduced fertility
- Blood transfusion complications, such as immune reactions and transmission of hepatitis
- Chelation complications, affecting the blood, liver, kidneys, vision, hearing and bones
- Gallstones see symptomatic cholelithiasis
Q: Alpha vs beta thalassemia - what are the main differences between them?
A: Thalassemia is an umbrella term that includes several diseases, all caused by a defect in the production of hemoglobin, the protein that enables red blood cells to carry oxygen. Normal hemoglobin has two alpha globin and two beta globin protein chains. Alpha and beta thalassemia are named after hereditary defects in these protein chains.
In their minor form, both alpha and beta thalassemia cause no symptoms, or only mild anemia. However, in their major forms, alpha is almost always fatal before birth, whereas beta is not immediately fatal because some production of healthy hemoglobin is still possible. However, without treatment there is severe anemia, and possible complications involving the bones, liver, spleen and heart.
Q: Can thalassemia be cured?
A: Stem cell transplantation is a possible cure for the condition. This involves high-dose chemotherapy to eliminate thalassemia-producing cells in the marrow, and subsequent replacement with normal blood-making cells from a donor, resulting in a lifelong cure if successful. However, there are potentially serious risks associated with stem cell transplantation, such as infection, organ failure, and even death. The level of risk depends on certain factors, including age of the patient, adequacy of previous chelation, and liver health.
Other names for thalassemia
Alpha (α) thalassemias
- Hb Barts
- Hemoglobin (Hb) Barts Hydrops Fetalis Syndrome (BHFS)
- Homozygous α0-thalassemia major
- Homozygous α-thalassemia 1
- Alpha thalassemia minor
- Silent alpha thalassemia carrier
- Hemoglobin H disease (HbH disease)
Beta (ß) thalassemias
- Cooley’s anemia
- Beta-zero (ß0) thalassemia
- Beta-plus (ß+) thalassemia
- Mediterranean anemia
- Beta thalassemia minor (beta thalassemia trait)
- Beta thalassemia intermedia
NCBI. “Growth and puberty and its management in thalassaemia." Accessed 16 April 2018. ↩