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
- Endocrinopathies (hormone problems) including diabetes, thyroid, adrenal and pituitary disorders
- Liver cirrhosis (swelling and scarring of the liver)
- 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
- Jaundice (yellow skin and eyes)
- Protruding abdomen
- Dark urine
- Facial bone deformities
- Slow growth
Causes of Thalassemia
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 and four normal genes (two from each parent) are required to make healthy alpha chains.
If a person inherits two faulty beta thalassemia genes (one from each parent), 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.
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, Diamond-Blackfan syndrome (a bone marrow disorder), 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.
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.
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