Thalassemia is an inherited blood disorder that affects the body’s ability to produce hemoglobin and red blood cells.

A person with thalassemia will have too few red blood cells and too little hemoglobin, and the red blood cells may be too small.

The impact of thalassemia can range from mild to severe and life threatening.

Thalassemia is the most common hereditary hemoglobin disorder, occurring in 4.4 out of 10,000 live births. It is most common in people with Mediterranean, South Asian, or African ancestry.

The symptoms of thalassemia vary depending on the type of thalassemia.

In infants with beta thalassemia and some types of alpha thalassemia, symptoms usually appear after the age of 6 months. This is because neonates have a different type of hemoglobin called fetal hemoglobin.

After 6 months, “normal” hemoglobin starts replacing the fetal type, and symptoms may begin to appear.

These include:

  • jaundice and pale skin
  • drowsiness and fatigue
  • chest pain
  • shortness of breath
  • rapid heartbeat
  • delayed growth
  • dizziness and faintness
  • greater susceptibility to infection

Skeletal deformities may result as the body tries to produce more bone marrow.

Iron may accumulate from blood transfusions. Excessive iron can harm the spleen, heart, and liver.

People with hemoglobin H, a form of alpha thalassemia, are more likely to develop gallstones and an enlarged spleen.

Untreated, the complications of thalassemia can potentially lead to organ failure.

Treatment depends on the type and severity of thalassemia.

  • Blood transfusions: These can replenish hemoglobin and red blood cell levels. People with thalassemia major will need between eight and 12 transfusions a year. Those with less severe thalassemia will need up to eight transfusions each year or more in times of stress, illness, or infection.
  • Iron chelation: This involves removing excess iron from the bloodstream. Sometimes, blood transfusions can cause iron overload. This can damage the heart and other organs. Doctors may prescribe deferoxamine, a medication given by injection under the skin or into the muscle. Or they may prescribe deferasirox, which a person takes by mouth.
  • Folic acid supplementation: People who receive blood transfusions and chelation may also need folic acid supplements. These help the red blood cells develop.
  • Bone marrow, or stem cell, transplant: Bone marrow cells produce red and white blood cells, hemoglobin, and platelets. In severe cases, a transplant from a compatible donor may be an effective treatment.
  • Surgery: This may be necessary to correct bone abnormalities.
  • Gene therapy: Scientists are investigating gene therapy techniques to treat thalassemia. Possibilities include inserting a normal beta-globin gene into a patient’s bone marrow or using drugs to reactivate the genes that produce fetal hemoglobin.

The protein hemoglobin transports oxygen around the body in blood cells. Bone marrow uses the iron a person gets from food to make hemoglobin.

In those with thalassemia, the bone marrow does not produce enough healthy hemoglobin or red blood cells. The body can also break down red blood cells with abnormal hemoglobin. Further, those red blood cells may not be flexible enough to squeeze through capillaries to reach necessary parts of the body. In some cases, these issues can lead to a lack of oxygen, resulting in anemia and fatigue.

People with mild thalassemia may not require any treatment, but more severe forms will necessitate regular blood transfusions.

Most children with moderate to severe thalassemia receive a diagnosis by the time they are 2 years old. People with no symptoms may not realize they are carriers until they have a child with thalassemia.

Blood tests can detect if a person is a carrier of thalassemia or has the condition. Here are the testing methods doctors use to help make a diagnosis:

  • Complete blood count (CBC): This can check hemoglobin levels and the level and size of red blood cells.
  • Reticulocyte count: This measures how fast reticulocytes, or immature red blood cells, are produced and released by the bone marrow. Reticulocytes usually spend around 2 days in the bloodstream before developing into mature red blood cells. Between 1 and 2 percent of a healthy person’s red blood cells are reticulocytes.
  • Iron levels: This will help the doctor determine the cause of anemia, whether thalassemia or iron deficiency. In thalassemia, iron deficiency is not the cause.
  • Genetic testing: DNA analysis will show whether a person has thalassemia or mutated genes.
  • Prenatal testing: This can show whether a fetus has thalassemia and how severe it might be.
  • Chorionic villus sampling (CVS): A piece of placenta is removed for testing, usually around the 11th week of pregnancy.
  • Amniocentesis: Healthcare professionals take a small sample of amniotic fluid for testing, usually during the 16th week of pregnancy. Amniotic fluid is the fluid that surrounds the fetus.

Thalassemia can be categorized in two ways: by the part of the hemoglobin affected and by the severity of the condition. The specific type of thalassemia a person has is typically due to inherited factors.

Alpha and beta

Four alpha-globin and two beta-globin protein chains make up hemoglobin. The two main types of thalassemia are alpha and beta.

Thalassemia can affect either part of the hemoglobin and may be referred to by that part. “Alpha thalassemia” indicates that the alpha part of hemoglobin is the affected part.

Severity

The terms “trait,” “minor,” “intermedia,” and “major” are used to indicate the severity of the disorder. For example, having the genetic trait for the disorder may produce no symptoms, while major thalassemia could produce severe symptoms leading to significant blood transfusions.

Identification terms explained

In alpha thalassemia, the hemoglobin does not produce enough alpha protein.

To make alpha-globin protein chains, a person needs four genes — two on each chromosome 16. People get two from each parent. If one or more of these genes is missing, alpha thalassemia will result.

The severity of thalassemia depends on how many genes are mutated.

  • One mutated gene: The person has no symptoms. A healthy person who has a child with symptoms of thalassemia is a carrier. This type is known as alpha thalassemia minima.
  • Two mutated genes: The person has mild anemia. It is known as alpha thalassemia minor.
  • Three mutated genes: The person has hemoglobin H disease, a type of chronic anemia. They will need regular blood transfusions throughout their life.
  • Four mutated genes: Alpha thalassemia major is the most severe form of alpha thalassemia. It is known to cause hydrops fetalis, a serious condition in which fluid accumulates in parts of a fetus’s body.

A fetus with four mutated genes cannot produce normal hemoglobin and is unlikely to survive, even with blood transfusions.

Alpha thalassemia is a more common type of thalassemia in southern China, Southeast Asia, India, the Middle East, and Africa.

Beta thalassemia

A person needs two globin genes to make beta-globin chains — one from each parent. If one or both genes are mutated, beta thalassemia will occur.

The severity depends on how many genes are mutated.

  • One mutated gene: This is called beta thalassemia minor.
  • Two mutated genes: There may be moderate or severe symptoms. This is known as thalassemia major. It used to be called Colley’s anemia.

Beta thalassemia is more common among people of Mediterranean ancestry. The prevalence is higher in North Africa and West Asia.

Various complications can arise from thalassemia.

Iron overload

This may be due to the frequent blood transfusions or the disease itself.

Iron overload raises the risk of hepatitis (swollen liver), fibrosis (scarring in the liver), and cirrhosis, or progressive liver damage due to scarring.

The endocrine glands produce hormones. The pituitary gland is particularly sensitive to iron overload. Damage may lead to delayed puberty and restricted growth. Later, there may be a higher risk of developing diabetes and either an underactive or overactive thyroid gland.

Iron overload also increases the risk of arrhythmias, or abnormal heart rhythms, and congestive heart failure.

Alloimmunization

Sometimes, a blood transfusion will trigger a reaction where the person’s immune system tries to destroy the new blood. It is important to have the exact blood type match to prevent this kind of problem.

Enlarged spleen

The spleen recycles red blood cells. In thalassemia, the red blood cells may have an abnormal shape, making it harder for the spleen to get rid of them through its natural process. The cells accumulate in the spleen, making it grow.

An enlarged spleen can become overactive. A person may need a splenectomy, or surgical removal of the spleen. This is less common now because removing the spleen can lead to other complications.

Infection

Removing the spleen leads to a higher chance of infection, and regular transfusions increase the risk of contracting a bloodborne disease.

Bone deformities

In some cases, the bone marrow expands, deforming the bone around it, especially the bones of the skull and face. The bone can become brittle, increasing the risk of fracture.

Thalassemia and pregnancy

Anyone considering pregnancy should first seek genetic counseling, especially if both partners have or may have thalassemia.

During pregnancy, a person with thalassemia may have a higher risk of cardiomyopathy and diabetes. There may be fetal growth restriction, too.

A cardiologist or hematologist should assess the pregnant partner before and during pregnancy to minimize problems, especially if they have thalassemia beta minor.

Doctors may recommend continuous fetal monitoring during delivery.

Depending on the type of thalassemia, constant medical care may be necessary to manage the condition effectively. Those receiving transfusions should be sure to follow their transfusion and chelation schedule.

Experts advise:

  • attending all regular appointments
  • maintaining contact with friends and support networks
  • following a balanced and nutrient-dense diet
  • getting a suitable amount of physical activity

People with thalassemia may have to avoid some foods, such as spinach or iron-enriched cereals, to prevent excessive iron buildup. People should discuss dietary and exercise options with their doctors.

The Centers for Disease Control and Prevention (CDC) urge people with thalassemia to keep their vaccinations up to date to prevent illness.

This is especially important for those who receive transfusions, as they have a higher risk of contracting hepatitis A or B.

The outlook depends on the type of thalassemia.

A person with the thalassemia trait has a typical life expectancy. However, heart complications arising from beta thalassemia major can make this condition fatal, though the outlook has improved in recent decades.