Thalassemia: Causes, Symptoms, Diagnosis

Thalassemia: Types, symptoms, and treatment

Thalassemia: Causes, Symptoms, Diagnosis

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 can range from mild to severe and life-threatening.

Around 100,000 newborns are delivered each year with severe forms of thalassemia. It is most common with Mediterranean, South Asian, and African ancestry.

Share on PinterestJaundice can be a symptom of thalassemia.

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

Symptoms will not show until the age of 6 months in most infants with beta thalassemia and some types of alpha thalassemia. 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
  • cold hands and feet
  • shortness of breath
  • leg cramps
  • rapid heart beat
  • poor feeding
  • delayed growth
  • headaches
  • dizziness and faintness
  • greater susceptibility to infections

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

If there is too much iron, the body will try to absorb more iron to compensate. Iron may also accumulate from blood transfusions. Excessive iron can harm the spleen, heart, and liver.

Patients with hemoglobin H are more ly to develop gallstones and an enlarged spleen.

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

Treatment depends on the type and severity of thalassemia.

Share on PinterestRegular blood transfusions may be necessary for people with some types of thalassemia.

Blood transfusions: These can replenish hemoglobin and red blood cell levels. Patients with thalassemia major will need between eight and twelve 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. Patients may be prescribed deferoxamine, a medication that is injected under the skin, or deferasirox, taken by mouth.

Patients 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. A transplant from a compatible donor may be an effective treatment, in severe cases.

Surgery: This may be necessary to correct bone abnormalities.

Gene therapy: Scientists are investigating genetic techniques to treat thalassemia. Possibilities include inserting a normal beta-globin gene into the 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 we get from food to make hemoglobin.

In people with thalassemia, the bone marrow does not produce enough healthy hemoglobin or red blood cells. In some types this leads 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.

Share on PinterestThalassemia is an inherited blood disorder.

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 that they are carriers until they have a child with thalassemia.

Blood tests can detect if a person is a carrier or if they have thalassemia.

A complete blood count (CBC): This can check levels of hemoglobin and the level and size of red blood cells.

A reticulocyte count: This measures how fast red blood cells, or reticulocytes, 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: 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 faulty 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: a small sample of amniotic fluid is taken for testing, usually during the 16th week of pregnancy. Amniotic fluid is the fluid that surrounds the fetus.

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

Alpha thalassemia

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

To make alpha-globin protein chains we need four genes, two on each chromosome 16. We 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 faulty, or mutated.

One faulty gene: The patient 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 faulty genes: The patient has mild anemia. It is known as alpha thalassemia minor.

Three faulty genes: The patient has hemoglobin H disease, a type of chronic anemia. They will need regular blood transfusions throughout their life.

Four faulty 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 the fetus’ body.

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

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

Beta Thalassemia

We need two globin genes to make beta-globin chains, one from each parent. If one or both genes are faulty, beta thalassemia will occur.

Severity depends on how many genes are mutated.

One faulty gene: This is called beta thalassemia minor.

Two faulty 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. Prevalence is higher in North Africa, West Asia, and the Maldive Islands.

Various complications can arise.

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.


Sometimes, a blood transfusion will trigger a reaction where the person’s immune system reacts to the new blood and tries to destroy it. 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 recycle them. The cells accumulate in the spleen, making it grow.

An enlarged spleen can become overactive. It can start to destroy the healthy blood cells the patient receives during transfusions. Sometimes, a patient may need a splenectomy, or surgical removal of the spleen. This is now less common, because removing the spleen can lead to other complications.


Removing the spleen leads to a higher chance of infection, and regular transfusions increase the risk of contracting a blood-borne 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.

Living with thalassemia

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

Share on PinterestA healthful diet and exercise are important, but patients should check with their doctors about how much iron-rich food, such as spinach, to consume.

People with thalassemia are advised to:

  • attend all their regular appointments
  • maintain contact with friends and support networks, to help keep a positive attitude
  • follow a healthy diet to maintain good health
  • get a suitable amount of exercise

Some foods, such as spinach or iron-enriched cereals, may have to be avoided, to prevent excessive iron buildup. Patients should discuss dietary and exercise options with their doctor.

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.

Thalassemia and pregnancy

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

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

The mother should be assessed by a cardiologist or hematologist before and during pregnancy, to minimize problems, especially if she has thalassemia beta minor.

During delivery, continuous fetal monitoring may be recommended.

The outlook depends on the type of thalassemia.

A person with the thalassemia trait has a normal life expectancy. However, heart complications arising from beta thalassemia major can make this condition fatal before the age of 30 years.


What Caused Thalassemias?

Thalassemia: Causes, Symptoms, Diagnosis

Your body makes three types of blood cells: red blood cells, white blood cells, and platelets (PLATE-lets). Red blood cells contain hemoglobin, an iron-rich protein that carries oxygen from your lungs to all parts of your body. Hemoglobin also carries carbon dioxide (a waste gas) from your body to your lungs, where it's exhaled.

Hemoglobin has two kinds of protein chains: alpha globin and beta globin. If your body doesn't make enough of these protein chains or they're abnormal, red blood cells won't form correctly or carry enough oxygen. Your body won't work well if your red blood cells don't make enough healthy hemoglobin.

Genes control how the body makes hemoglobin protein chains. When these genes are missing or altered, thalassemias occur.

Thalassemias are inherited disorders—that is, they're passed from parents to children through genes. People who inherit faulty hemoglobin genes from one parent but normal genes from the other are called carriers. Carriers often have no signs of illness other than mild anemia. However, they can pass the faulty genes on to their children.

People who have moderate to severe forms of thalassemia have inherited faulty genes from both parents.

Alpha Thalassemias

You need four genes (two from each parent) to make enough alpha globin protein chains. If one or more of the genes is missing, you'll have alpha thalassemia trait or disease. This means that your body doesn't make enough alpha globin protein.

  • If you're only missing one gene, you're a “silent” carrier. This means you won't have any signs of illness.
  • If you're missing two genes, you have alpha thalassemia trait (also called alpha thalassemia minor). You may have mild anemia.
  • If you're missing three genes, you ly have hemoglobin H disease (which a blood test can detect). This form of thalassemia causes moderate to severe anemia.

Very rarely, a baby is missing all four genes. This condition is called alpha thalassemia major or hydrops fetalis. Babies who have hydrops fetalis usually die before or shortly after birth.

Example of an Inheritance Pattern for Alpha Thalassemia

Beta Thalassemias

You need two genes (one from each parent) to make enough beta globin protein chains. If one or both of these genes are altered, you'll have beta thalassemia. This means that your body won’t make enough beta globin protein.

  • If you have one altered gene, you're a carrier. This condition is called beta thalassemia trait or beta thalassemia minor. It causes mild anemia.
  • If both genes are altered, you'll have beta thalassemia intermedia or beta thalassemia major (also called Cooley's anemia). The intermedia form of the disorder causes moderate anemia. The major form causes severe anemia.

Example of an Inheritance Pattern for Beta Thalassemia


What is Thalassemia? | CDC

Thalassemia: Causes, Symptoms, Diagnosis

Thalassemia is an inherited (i.e.

, passed from parents to children through genes) blood disorder caused when the body doesn’t make enough of a protein called hemoglobin, an important part of red blood cells.

When there isn’t enough hemoglobin, the body’s red blood cells don’t function properly and they last shorter periods of time, so there are fewer healthy red blood cells traveling in the bloodstream.

Red blood cells carry oxygen to all the cells of the body. Oxygen is a sort of food that cells use to function.

When there are not enough healthy red blood cells, there is also not enough oxygen delivered to all the other cells of the body, which may cause a person to feel tired, weak or short of breath.

This is a condition called anemia. People with thalassemia may have mild or severe anemia. Severe anemia can damage organs and lead to death.

What are the different types of thalassemia?

When we talk about different “types” of thalassemia, we might be talking about one of two things: the specific part of hemoglobin that is affected (usually either “alpha” or “beta”), or the severity of thalassemia, which is noted by words trait, carrier, intermedia, or major.

Hemoglobin, which carries oxygen to all cells in the body, is made of two different parts, called alpha and beta.

When thalassemia is called “alpha” or “beta,” this refers to the part of hemoglobin that isn’t being made.

If either the alpha or beta part is not made, there aren’t enough building blocks to make normal amounts of hemoglobin. Low alpha is called alpha thalassemia. Low beta is called beta thalassemia.

When the words “trait,” “minor,” “intermedia,” or “major” are used, these words describe how severe the thalassemia is. A person who has thalassemia trait may not have any symptoms at all or may have only mild anemia, while a person with thalassemia major may have severe symptoms and may need regular blood transfusions.

In the same way that traits for hair color and body structure are passed down from parents to children, thalassemia traits are passed from parents to children.

The type of thalassemia that a person has depends on how many and what type of traits for thalassemia a person has inherited, or received from their parents.

For instance, if a person receives a beta thalassemia trait from his father and another from his mother, he will have beta thalassemia major.

If a person received an alpha thalassemia trait from her mother and the normal alpha parts from her father, she would have alpha thalassemia trait (also called alpha thalassemia minor). Having a thalassemia trait means that you may not have any symptoms, but you might pass that trait on to your children and increase their risk for having thalassemia.

Sometimes, thalassemias have other names, Constant Spring, Cooley’s Anemia, or hemoglobin Bart hydrops fetalis. These names are specific to certain thalassemias – for instance, Cooley’s Anemia is the same thing as beta thalassemia major.

How do I know if I have thalassemia?

People with moderate and severe forms of thalassemia usually find out about their condition in childhood, since they have symptoms of severe anemia early in life. People with less severe forms of thalassemia may only find out because they are having symptoms of anemia, or maybe because a doctor finds anemia on a routine blood test or a test done for another reason.

Because thalassemias are inherited, the condition sometimes runs in families. Some people find out about their thalassemia because they have relatives with a similar condition.

People who have family members from certain parts of the world have a higher risk for having thalassemia.

Traits for thalassemia are more common in people from Mediterranean countries, Greece and Turkey, and in people from Asia, Africa, and the Middle East.

If you have anemia and you also have family members from these areas, your doctor might test your blood further to find out if you have thalassemia.

Can I prevent thalassemia?

Because thalassemia is passed from parents to children, it is very hard to prevent.

However, if you or your partner knows of family members with thalassemia, or if you both have family members from places in the world where thalassemia is common, you can speak to a genetic counselor (go to: https://www. icon) to determine what your risk would be of passing thalassemia to your children.


Signs, Symptoms, and Complications of Thalassemias

Thalassemia: Causes, Symptoms, Diagnosis

A lack of oxygen in the bloodstream causes the signs and symptoms of thalassemias. The lack of oxygen occurs because the body doesn't make enough healthy red blood cells and hemoglobin. The severity of symptoms depends on the severity of the disorder.

No Symptoms

Alpha thalassemia silent carriers generally have no signs or symptoms of the disorder. The lack of alpha globin protein is so minor that the body's hemoglobin works normally.

Mild Anemia

People who have alpha or beta thalassemia trait can have mild anemia. However, many people who have these types of thalassemia have no signs or symptoms.

Mild anemia can make you feel tired. Mild anemia caused by alpha thalassemia trait might be mistaken for iron-deficiency anemia.

Mild to Moderate Anemia and Other Signs and Symptoms

People who have beta thalassemia intermedia have mild to moderate anemia. They also may have other health problems, such as:

  • Slowed growth and delayed puberty. Anemia can slow down a child's growth and development.
  • Bone problems. Thalassemia may cause bone marrow to expand. Bone marrow is the spongy substance inside bones that makes blood cells. When bone marrow expands, the bones become wider than normal. They may become brittle and break easily.
  • An enlarged spleen. The spleen is an organ that helps your body fight infection and remove unwanted material. When a person has thalassemia, the spleen has to work very hard. As a result, the spleen becomes larger than normal. This makes anemia worse. If the spleen becomes too large, it must be removed.

Severe Anemia and Other Signs and Symptoms

People who have hemoglobin H disease or beta thalassemia major (also called Cooley's anemia) have severe thalassemia. Signs and symptoms usually occur within the first 2 years of life. They may include severe anemia and other health problems, such as:

  • A pale and listless appearance
  • Poor appetite
  • Dark urine (a sign that red blood cells are breaking down)
  • Slowed growth and delayed puberty
  • Jaundice (a yellowish color of the skin or whites of the eyes)
  • An enlarged spleen, liver, or heart
  • Bone problems (especially with bones in the face)

Complications of Thalassemias

Better treatments now allow people who have moderate and severe thalassemias to live much longer. As a result, these people must cope with complications of these disorders that occur over time.

Heart and Liver Diseases

Regular blood transfusions are a standard treatment for thalassemias. Transfusions can cause iron to build up in the blood (iron overload). This can damage organs and tissues, especially the heart and liver.

Heart disease caused by iron overload is the main cause of death in people who have thalassemias. Heart disease includes heart failure, arrhythmias (irregular heartbeats), and heart attack.


Many people who have thalassemias have bone problems, including osteoporosis (OS-te-o-po-RO-sis). This is a condition in which bones are weak and brittle and break easily.

Source: National Heart, Lung, and Blood Institute, National Institutes of Health.


Thalassemia Blood Disorder

Thalassemia: Causes, Symptoms, Diagnosis

Red blood cells transport oxygen throughout the body; hemoglobin is the protein in red blood cells that actually carries the oxygen. Thalassemia (thal-uh-SEE-me-uh) is a group of disorders that affect the body's ability to produce normal hemoglobin.

People who have thalassemia produce fewer healthy hemoglobin proteins, and their bone marrow produces fewer healthy red blood cells.

Thalassemias can cause mild or severe anemia and other complications that can occur over time (such as iron overload). Symptoms of anemia include fatigue, difficulty breathing, dizziness, and a pale skin tone.

Who is at risk for thalassemia?

Thalassemias occur more often among certain ethnicities, including people of Italian, Greek, Middle Eastern, Asian, and African descent. Thalassemias are an inherited disorder, which means they are passed from a parent to their child.

What are the types of thalassemia?

Four protein chains make up hemoglobin — 2 alpha globin and 2 beta globin chains. There are 2 major types of thalassemia – alpha thalassemia and beta thalassemia – named after defects that can occur in these protein chains.

Alpha Thalassemia

Four genes, 2 from each parent, are required to make alpha globin protein chains. When 1 or more genes are missing, it produces alpha thalassemia. This chart describes the different types of alpha thalassemia.

  • Missing alpha genes: 1
    • Disorder: silent carrier
    • Anemia symptoms: none
    • Other names: Alpha thalassemia – 2 trait, alpha thalassemia minima
  • Missing alpha genes: 2
    • Disorder: trait
    • Anemia symptoms: mild
    • Other names: Alpha thalassemia – 1 trait, alpha thalassemia minor
  • Missing alpha genes: 3
    • Disorder: Hemoglobin H
    • Anemia symptoms: moderate
    • Other names: Hemoglobin H disease
  • Missing alpha genes: 4
    • Disorder: major
    • Anemia symptoms: fatal
    • Other names: Hydrops fetalis with Hemoglobin Barts

What are the symptoms of alpha thalassemia?

People who are missing one alpha gene (silent carriers) usually don't have any symptoms. Hemoglobin H disease often causes symptoms at birth and may cause moderate to severe lifelong anemia.

Beta Thalassemia

There are normally 2 beta globin genes, one from each parent. Beta thalassemia is a change in 1 or both of the beta globin genes. This chart describes the different types of beta thalassemia.

  • Affected beta genes:1
    • Disorder: silent carrier
    • Anemia symptoms: mild
    • Other names: Beta thalassemia minor
  • Affected beta genes: 1
    • Disorder: trait
    • Anemia symptoms: mild
  • Affected beta genes: 2
    • Disorder: intermedia
    • Anemia symptoms: moderate
  • Affected beta genes: 2
    • Disorder: major
    • Anemia symptoms: severe
    • Other names: Cooley's anemia

What are the symptoms of beta thalassemia?

Symptoms of beta thalassemia include growth problems, bone abnormalities such as osteoporosis, and an enlarged spleen (the organ in the abdomen that plays a part in fighting infection).

People with thalassemia can get too much iron in their bodies (iron overload), either from frequent blood transfusions or from the disease itself. Too much iron can cause damage to your heart, liver, and endocrine system, which includes glands that produce hormones that regulate processes throughout your body.

People who have thalassemias may suffer severe infections. One reason may be the large number of blood transfusions these patients need; the infections may be carried in the blood that they receive in a transfusion.

Last reviewed by a Cleveland Clinic medical professional on 07/14/2018.




Thalassemia: Causes, Symptoms, Diagnosis

Thalassemia is a blood condition. If you have it, your body has fewer red blood cells and less hemoglobin than it should. Hemoglobin is important because it lets your red blood cells carry oxygen to all parts of your body.

Treatment is the key to living longer and better. There are also steps you can take to stay as healthy as possible.

Thalassemia is genetic. You inherit it from your parents and you have it from birth. You can’t catch thalassemia the way you catch a cold or the flu.

Thalassemia is really a group of blood problems, not just one.

To make hemoglobin you need two proteins, alpha and beta. Without enough of one or the other, your red blood cells can’t carry oxygen as they should.

Alpha thalassemia means you lack alpha hemoglobin. With beta thalassemia, you lack beta hemoglobin.

Your doctor may also talk about thalassemia minor and thalassemia major, or Cooley’s anemia. The minor type is less serious than the major one, and your type won’t change.

These can include:

In some people, symptoms show up at birth. In others, it can take a couple of years to see anything. Some people who have thalassemia will show no signs at all.

If you think you may have thalassemia, and if your parents have it, you should see a doctor. She will examine you and will ask questions.

You’ll take blood tests. One is a CBC (complete blood count) test. The other is a hemoglobin electrophoresis test. If you are pregnant or trying to have a baby, there are tests that can be done before birth to learn if the baby will have the condition.

If you do have thalassemia, you should see a blood expert known as a hematologist. You may also need other special doctors on your team, those who treat the heart or liver.

With a mild case, you may feel tired and not need treatment. But if it’s more serious, your organs may not get the oxygen they need.

You might have to get regular blood transfusions. A transfusion is a way to get donated blood or parts of blood that your body needs, hemoglobin.

How often you need transfusions can vary. Some people have one every few weeks. Your transfusion schedule may change as you get older.

Blood transfusions are important for people with thalassemia. But they can cause too much iron in the blood. That can lead to problems with the heart, liver, and blood sugar. If you get transfusions, you and your doctor will talk about whether you need medicine that can help remove extra iron from your body.

Sometimes, transfusions of blood cause reactions high fever, nausea, diarrhea, chills, and low blood pressure. If you have any of these, see your doctor. Donated blood in the U.S. is very safe. But there’s a remote chance that you could get an infection from a blood transfusion.

Some people with severe thalassemia have other health problems, heart or liver disease. Your bones may become thin and brittle. You may be shorter than others because your bones don’t grow normally. And the bones in your face can look shape or distorted.

These problems don’t happen to everyone who has thalassemia.

No, you can’t prevent thalassemia, since it’s in your genes.

If you have it and you want to have children, you might want to talk with a genetics counselor. This is an expert in health issues that are passed down through families. The counselor will explain your chance of having a child with thalassemia.

You’ll want to work closely with your doctor and keep up with your treatments.

If you have thalassemia, follow these habits to stay well:

  • Don’t take iron pills.
  • Eat a healthy diet to keep your bones strong and give you energy.
  • Ask your doctor about supplements calcium and vitamin D.
  • Stay away from sick people and wash your hands often.
  • If you get a fever or feel ill, see your doctor.

You may also want to look into joining a support group, so you can connect with other people who have the condition.


Mayo Clinic: “Thalassemia.”

Cooley’s Anemia Foundation: “A Guide to Living with Thalassemia.”

Thalassemia Support Foundation: “About Thalassemia.”

Children’s Cancer and Blood Foundation: “Thalassemia: (Cooley’s Anemia).”

National Institutes of Health. National Heart, Lung, and Blood Institute: “What Are the Signs and Symptoms of Thalassemias?

Cooley’s Anemia Foundation: “Clinical Trials.”

© 2018 WebMD, LLC. All rights reserved.


Beta Thalassemia – NORD (National Organization for Rare Disorders)

Thalassemia: Causes, Symptoms, Diagnosis

The symptoms and severity of beta thalassemia varies greatly from one person to another. Individuals with beta thalassemia minor do not develop symptoms of the disorder but may have a mild anemia. Many individuals with beta thalassemia minor go through life never knowing they carry an altered gene for the disorder.

A beta thalassemia major diagnosis is usually made during the first two years of life and individuals require regular blood transfusions and lifelong medical care to survive. When the disorder develops later during life, a diagnosis of beta thalassemia intermedia is given; individuals may only require blood transfusions on rare, specific instances.

Beta thalassemia major, also known as Cooley’s anemia, is the most severe form of beta thalassemia. Affected infants exhibit symptoms within the first two years of life, often between 3 and 6 months after birth.

The full or classic “description” of beta thalassemia major tends to primarily occur in developing countries. Most individuals will not develop the severe symptoms discussed below.

Although beta thalassemia major is a chronic, lifelong illness, if individuals follow the current recommended treatments, most individuals can live happy, fulfilling lives.

Severe anemia develops and is associated with fatigue, weakness, shortness of breath, dizziness, headaches, and yellowing of the skin, mucous membranes and whites of the eyes (jaundice).

Affected infants often fail to grow and gain weight as expected based upon age and gender (failure to thrive). Some infants become progressively pale (pallor).

Feeding problems, diarrhea, irritability or fussiness, recurrent fevers, abnormal enlargement of the liver (hepatomegaly), and the abnormal enlargement of the spleen (splenomegaly) may also occur.

Splenomegaly may cause abdominal enlargement or swelling.

Splenomegaly may be associated with an overactive spleen (hypersplenism), a condition that can develops because too many blood cells build up and are destroyed within the spleen.

Hypersplenism can contribute to anemia in individuals with beta thalassemia and cause low levels of white blood cells, increasing the risk of infection, and low levels of platelets, which can lead to prolonged bleeding.

If untreated, additional complications can develop. Beta thalassemia major can cause the bone marrow, the spongy material within certain bones, to expand. Bone marrow is where most of the blood cells are produced in the body. The bone marrow expands because it is trying to compensate for chronic anemia.

This abnormal expansion causes bones to become thinner, wider and brittle. Affected bones may grow abnormally (bone deformities), particularly the long bones of the arms and legs and certain bones of the face.

When facial bones are affected it can result in distinctive facial features including an abnormally prominent forehead (frontal bossing), full cheek bones (prominent malar eminence), a depressed bridge of the nose, and overgrowth (hypertrophy) of the upper jaw (maxillae), exposing the upper teeth.

The affected bones have an increased fracture risk, particularly the long bones of the arms and legs. Some individuals may develop ‘knock knees’ (genu valgum), a condition in which the legs bend inward so that when a person is standing the knees will touch even if the ankles and feet are not.

Even when treated, complications may develop, specifically the buildup of iron in the body (iron overload). Iron overload results from the blood transfusions required to treat individuals with beta thalassemia major.

In addition, affected individuals experience greater iron absorption from the gastrointestinal tract, which contributes to iron overload (although this primarily occurs in untreated individuals).

Iron overload can cause tissue damage and impaired function of affected organs such as the heart, liver and endocrine glands.

Iron overload can damage the heart causing abnormal heart rhythms, inflammation of the membrane (pericardium) that lines the heart (pericarditis), enlargement of the heart and disease of the heart muscle (dilated cardiomyopathy).

Heart involvement can progress to life-threatening complications such as heart failure. Liver involvement can cause scarring and inflammation of the liver (cirrhosis) and high pressure of the main liver vein (portal hypertension). Endocrine gland involvement can cause insufficiency of certain glands such as the thyroid (hypothyroidism) and, in rare cases, diabetes mellitus. Iron overload can also be associated with growth retardation and the failure or delay of sexual maturation.

Additional symptoms that may occur include masses that form because of blood cell production outside of the bone marrow (extramedullary hematopoiesis).

These masses primarily form in the spleen, liver, lymph nodes, chest, and spine and can potentially cause compression of nearby structures and a variety of symptoms.

Affected individuals may develop leg ulcers, an increased risk of developing blood clots within a vein (venous thrombosis) and decreased bone mineralization resulting in brittle bones that are prone to fracture (osteoporosis).

Individuals diagnosed with beta thalassemia intermedia have a widely varied expression of the disorder. Moderately severe anemia is common and affected individuals may require periodic blood transfusions.

Each individual case is unique. Common symptoms include pallor, jaundice, leg ulcers, gallstones (cholelithiasis), and abnormal enlargement of the liver and spleen.

Moderate to severe skeletal malformations (as described in beta thalassemia major) may also occur.

Dominant beta thalassemia is an extremely rare form in which individuals who have one mutated HBB gene develop certain symptoms associated with beta thalassemia. Affected individuals may develop mild to moderate anemia, jaundice, and an abnormally enlarged spleen (splenomegaly).


The Beta Thalassemia Trait: Anemia Symptoms, Treatment & Diagnosis

Thalassemia: Causes, Symptoms, Diagnosis

People with thalassemia make defective hemoglobin, the compound in blood that carries oxygen.

  • Thalassemias are inherited blood disorders.
  • Thalassemia patients make defective hemoglobin.
  • There are two forms of beta thalassemia: thalassemia minor and thalassemia major (also called Cooley's anemia).
  • Beta thalassemia is classically described in people of Italian and Greek origin.

What are the thalassemias?

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The thalassemias are a group of genetic (inherited) blood disorders that share in common one feature, the defective production of hemoglobin, the protein that enables red blood cells to carry and deliver oxygen. There are many different mechanisms of defective hemoglobin synthesis and, hence, many types of thalassemia.

What is the most common type of thalassemia?

The most familiar type of thalassemia is beta thalassemia. It involves decreased production of normal adult hemoglobin (Hb A), the predominant type of hemoglobin from soon after birth until death. (All hemoglobin consists of two parts: heme and globin).

The globin part of Hb A has 4 protein sections called polypeptide chains. Two of these chains are identical and are designated the alpha chains. The other two chains are also identical to one another but differ from the alpha chains and are termed the beta chains.

In persons with beta thalassemia, there is reduced or absent production of beta globin chains.

What is the difference between thalassemia minor and major?

There are two forms of beta thalassemia. They are thalassemia minor and thalassemia major (which is also called Cooley's anemia).

Thalassemia minor: The individual with thalassemia minor has only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be heterozygous for beta thalassemia.

Persons with thalassemia minor have (at most) mild anemia (slight lowering of the hemoglobin level in the blood). This situation can very closely resemble that with mild iron-deficiency anemia.

However, persons with thalassemia minor have a normal blood iron level (unless they are iron deficient for other reasons). No treatment is necessary for thalassemia minor.

In particular, iron is neither necessary nor advised.

Thalassemia major (Cooley's anemia): The child born with thalassemia major has two genes for beta thalassemia and no normal beta-chain gene. The child is homozygous for beta thalassemia. This causes a striking deficiency in beta chain production and in the production of Hb A. Thalassemia major is a significant illness.

The clinical picture associated with thalassemia major was first described in 1925 by the American pediatrician Thomas Cooley. Hence, the name Cooley's anemia in his honor.

At birth the baby with thalassemia major seems entirely normal. This is because the predominant hemoglobin at birth is still fetal hemoglobin (HbF). HbF has two alpha chains ( Hb A) and two gamma chains (un Hb A). It has no beta chains so the baby is protected at birth from the effects of thalassemia major.

Anemia begins to develop within the first months after birth. It becomes progressively more and more severe. The infant fails to thrive (to grow normally) and often has problems feeding (due to easy fatigue from lack of oxygen due to the profound anemia), bouts of fever, diarrhea, and other intestinal problems.

Anemia Symptoms and Signs, Types, Treatment and Causes See Slideshow

What is Mediterranean anemia?

The gene for beta thalassemia is not evenly distributed among peoples. It is, for example, relatively more frequent in people of Italian and Greek origin, both of which are peoples from the Mediterranean. Because of this, thalassemia major has been called Mediterranean anemia.

The name thalassemia was coined at the University of Rochester in upstate New York by the Nobel Prize-winning pathologist George Whipple and the professor of pediatrics William Bradford from the Greek thalassa for sea and -emia, meaning the blood. Thalassemia means “sea in the blood.” But for the Greeks, the sea was the Mediterranean, so thalassemia also conveys the idea of the Mediterranean in the blood.

The reason that the gene for beta thalassemia is relatively common, for example, among people of Italian and Greek origin is that parts of Italy and Greece were once full of malaria. The presence of thalassemia minor ( sickle cell trait in Africa) afforded protection against malaria, and therefore, this gene thrived.

What is the genetic pattern of inheritance of beta thalassemia?

The pattern of genetic transmission of beta thalassemia (and sickle cell disease) was deciphered by James V. Neel when he was at the University of Rochester (and later at the University of Michigan). Dr. Neel recognized that the parents of children with thalassemia major had thalassemia minor with one beta thalassemia gene.

When these parents had children, they have a 25% chance of having a thalassemia major child (with both genes for beta thalassemia), a 50% chance of having children with thalassemia minor (with only one gene for beta thalassemia), and a 25% chance of having a child without thalassemia major or minor (with both genes for normal beta chains).

This form of inheritance is medically referred to as an autosomal recessive pattern.

The diagnosis of thalassemia major and minor

Persons with thalassemias have smaller sized red blood cells than unaffected people as well as low red blood cell counts (anemia).

Thalassemia major and thalassemia minor can now be diagnosed (and distinguished from one another) not only by conventional clinical and blood testing, but also by molecular and genetic tests.

These tests permit accurate diagnosis to be made at any time, even before birth (in fact, well before the beta chains are even synthesized).

The treatment of thalassemia major

Infants with thalassemia major are well at birth because of a special form of hemoglobin present in the fetus and newborn. Eventually, however, this hemoglobin is replaced by defective hemoglobin. Symptoms emerge late in the first year of life.

The child develops pale skin, irritability, growth retardation, swelling of the abdomen due to enlargement of the liver and spleen (hepatosplenomegaly) with jaundice. This is associated with severe anemia with rupture of the red blood cells (hemolytic anemia).

The child with thalassemia major becomes dependent on blood transfusions and, although they do help, they create further problems including iron overload. Folic acid supplementation is often given. At this time, the primary treatments are directed at relieving symptoms of the illness.

Selected patients may qualify for bone marrow or stem cell transplants. Gene therapy remains a potential treatment for the future.

The long-term hope is that thalassemia major will be cured by insertion of the normal beta-chain gene through gene therapy or by another modality of molecular medicine.

Additional information is also available through the following organizations:

The National Institutes of Health (NIH)Cellular Hematology Scientific Research Group

Blood Diseases Program

National Heart, Lung, and Blood Institute6701 Rockledge Drive, MSC-7950Bethesda, MD 20892-7950. USAPhone: 301-435-0050

Fax: 301-480-0868

Cooley's Anemia Foundation,129-09 26th Avenue – #203Flushing, NY 11354, USAPhone: 800-522-7222Fax: 718-321-3340

Thalassemia International FederationPhilippou Hadjigerogiou No.1- Flat 8P.O. Box 8807Nicosia, CyprusPhone: (357) 2-319129

Fax: (357) 2-314552

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Medically Reviewed on 12/11/2019


Kasper, D.L., et al., eds. Harrison's Principles of Internal Medicine, 19th Ed. United States: McGraw-Hill Education, 2015.