Alpha Thalassemia

Alpha thalassemia is an inherited blood disorder that reduces the body’s ability to produce hemoglobin, the protein in red blood cells that carries oxygen throughout the body. The severity can range from having no symptoms at all to life-threatening complications before or shortly after birth.

Table of contents

• What is Alpha Thalassemia?
• Causes and Inheritance
• Types of Alpha Halassemia
• Signs and Symptoms
• Who is Affected?
• Diagnosis
• Treatment
• Living with Alpha Thalassemia

What is Alpha Thalassemia?

Alpha thalassemia is a blood disorder that affects your body’s ability to make enough hemoglobin, the protein inside red blood cells that carries oxygen to all parts of your body^[1]. When your body cannot make enough hemoglobin, you also have fewer healthy red blood cells. This means your body’s tissues do not get enough oxygen, which can cause you to feel tired and weak^[2].

The condition is inherited, which means it is passed down from parents to their children through genes^[1]. Alpha thalassemia is named after problems in the alpha globin protein chains that make up part of hemoglobin^[3].

Causes and Inheritance

Hemoglobin is made up of four protein chains: two alpha chains and two beta chains. Each chain contains genetic information passed down from your parents^[2]. Alpha thalassemia happens when there are problems with the genes that tell your body how to make the alpha chains.

Every person has four genes that make alpha globin protein. You inherit two genes from your mother and two from your father^[1]. Alpha thalassemia typically results from deletions, or missing pieces, in one or more of these genes. Less commonly, changes to the DNA sequence in or near these genes can cause alpha thalassemia. These changes are often called nondeletion variants, and they tend to be more severe than deletions^[1].

Alpha thalassemia major is an inherited autosomal recessive disease. This means that a baby will have the most severe form only if they receive two nonfunctioning genes from each parent, for a total of four nonfunctioning genes. If both parents have two nonfunctioning genes, there is a 1 in 4, or 25%, chance that their baby will inherit all four nonfunctioning genes and have alpha thalassemia major^[13].

Types of Alpha Thalassemia

The type of alpha thalassemia you have depends on how many of your four alpha globin genes are defective or missing. The more genes that are affected, the more severe the condition^[2].

Alpha thalassemia carrier (or silent carrier): This happens when one gene is defective or missing. People with this type usually have no signs or symptoms of anemia and do not need any special medical treatment^[4]. Another name for this condition is alpha thalassemia minima^[2].

Alpha thalassemia trait (or alpha thalassemia minor): This occurs when two genes are defective or missing. People with this type may have mild anemia but usually do not need any medical treatment^[4]. A trait is different from a disease. Most people with alpha thalassemia trait have no signs or symptoms of illness, though the trait can sometimes cause mild anemia^[5].

Hemoglobin H disease: This results when three of the four alpha globin genes are defective or missing, which sharply reduces the amount of normal alpha globin produced^[1]. People with hemoglobin H disease have moderate to severe anemia^[2]. The features of hemoglobin H disease usually appear in early childhood, and affected individuals typically live into adulthood^[1].

Alpha thalassemia major (or hemoglobin Bart hydrops fetalis): This is the most severe form and results from the loss or alteration of all four alpha globin genes. Such changes prevent the production of any normal alpha globin^[1]. Without treatment, most babies with this condition are stillborn or die soon after birth because of serious health problems^[1].

Signs and Symptoms

The symptoms of alpha thalassemia depend on which type you have. People who are carriers or have alpha thalassemia trait usually have no symptoms or only very mild anemia^[4].

Children with hemoglobin H disease or alpha thalassemia major have symptoms of anemia, which may include^[4]:

• Extreme tiredness or fatigue
• Pale skin
• Shortness of breath or trouble breathing
• A fast heartbeat
• Yellow skin and eyes, called jaundice
• Moodiness or irritability
• Slow growth
• Changes in the shape of bones in the face and head

Hemoglobin H disease causes mild to moderate anemia, an enlarged liver and spleen (called hepatosplenomegaly), and yellowing of the eyes and skin^[1].

Hemoglobin Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs can include severe anemia, an enlarged liver and spleen, heart defects, and abnormalities of the urinary system or genitalia^[1]. This condition can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (called preeclampsia), premature delivery, and abnormal bleeding^[1].

People with hemoglobin H disease and alpha thalassemia major may also build up extra iron in the body, either from the disease itself or from frequent blood transfusions. Extra iron can damage the heart, liver, and endocrine system, which is the system of glands that makes hormones^[4].

Who is Affected?

Alpha thalassemia is a fairly common blood disorder worldwide. Thousands of infants with hemoglobin Bart syndrome and hemoglobin H disease are born each year, particularly in Southeast Asia^[1]. Alpha thalassemia also occurs frequently in people from Mediterranean countries, Africa, the Middle East, India, and Central Asia^[1].

The gene changes that cause thalassemia arose in humanity as partial protections against malaria. So thalassemia affects people who have ancestral links to parts of the world where malaria is common, such as Africa, Southern Europe, and West, South and East Asia^[2]. Having a mild form of alpha thalassemia has been shown to protect against malaria and thus can be an advantage in areas where malaria is common^[3].

Diagnosis

Diagnosis involves checking the medical history of near relatives, microscopic examination of a blood smear, ferritin test, hemoglobin electrophoresis, and DNA sequencing^[3].

Preliminary screening of parents for alpha thalassemia is performed by a simple blood test called a complete blood count, or CBC. If the results show a reduced mean corpuscular volume (MCV), which measures the size of red blood cells, and the parents have normal iron status (meaning they are not anemic because of iron deficiency), then specific testing for hereditary anemias including alpha thalassemia should be performed^[13].

Specific testing for thalassemia includes hemoglobin typing and alpha globin common mutation analysis^[13]. Because alpha thalassemia major is a serious condition that can affect both the fetus and the mother, early diagnosis and treatment during pregnancy are critical^[13].

Treatment

Treatments for alpha thalassemia depend on the type and how serious it is. If you are a carrier or have alpha thalassemia trait, you likely have mild or no symptoms and may not need treatment^[10].

Blood Transfusions

Blood transfusions are the main way to treat moderate or severe alpha thalassemia. This treatment gives you red blood cells with healthy hemoglobin^[10]. During a blood transfusion, a needle is used to insert a tube into one of your blood vessels, and you receive healthy blood through this line. The procedure usually takes 1 to 4 hours^[10].

Some people with hemoglobin H disease need frequent blood transfusions to help them grow and develop well. Others do not but might need transfusions during certain times, such as when your body is under stress from an infection, pregnancy, or surgery^[4]. People with alpha thalassemia major need frequent blood transfusions after birth to survive^[4].

Iron Chelation Therapy

The hemoglobin 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^[10]. To prevent this, doctors use iron chelation therapy in people who receive regular blood transfusions to remove excess iron from the body^[10].

Three medicines are used for iron chelation therapy. The type prescribed depends on factors like age and how well organs are working^[10]. Iron supplementation does not improve blood values in alpha thalassemia. In fact, many patients with apparent iron deficiency actually have iron overload, which can contribute to illness^[9].

Folic Acid and Other Supportive Care

Folic acid supplementation may be beneficial in patients with hemoglobin H disease who have elevated reticulocyte counts, which are young red blood cells that indicate the body is trying to make more red blood cells^[9].

In hemoglobin H disease, general supportive care, including transfusions, may be needed periodically or during periods of severe anemia, such as during a viral infection^[9]. Blood transfusions should be administered only if necessary^[9].

Surgery

Doctors might need to remove the spleen if it gets too big or causes pain. The spleen helps fight some infections, so people who have had their spleen removed are at higher risk for infections and need to take special precautions^[4].

Advanced Treatments

In very severe cases, bone marrow transplant from a well-matched donor may be considered^[3]. This measure can be curative because the blood-making system of the patient is replaced by that of the donor^[9].

For pregnancies affected by alpha thalassemia major, fetal therapy options include fetal transfusions and fetal stem cell transplantation. Early diagnosis and treatment are critical for the survival of the fetus and the health of the mother^[13].

Living with Alpha Thalassemia

For people with thalassemia, a healthy lifestyle means managing the disorder and making healthy choices^[14]. The most important thing a person with thalassemia can do is stick to their transfusion and chelation schedules to prevent severe anemia and possible organ damage from iron overload^[14].

Vaccinations

Children and adults with thalassemia should get all recommended vaccinations, including a flu vaccination. People with thalassemia are considered at high risk for certain infections, especially if they have had their spleen removed^[14]. It is important to be aware of the risk of infections, particularly in children who have undergone splenectomy, and to administer appropriate vaccines^[9].

Nutrition

Eating nutritious foods is important for everyone. For people living with alpha thalassemia, because too much iron may build up in the blood, foods high in iron may need to be limited^[14]. Iron can be found in meat, fish, and some vegetables like spinach. Other products, like cereal and orange juice, may contain extra iron. Persons with thalassemia should discuss with their doctor whether or not they should limit the amount of iron in their diet^[14].

In patients with hemoglobin H disease and elevated ferritin levels (which measure iron in the body), the diet should be low in iron^[9].

Exercise

Exercise is part of an overall healthy lifestyle and helps lead to better health outcomes. Although some people with thalassemia may have trouble participating in vigorous forms of exercise, many people with thalassemia can participate in moderate physical activities including biking, running, and walking^[14]. Regular physical exercise can improve your mood and help strengthen your bones^[15].

Pregnancy

Women with thalassemia major or other severe types can have a healthy pregnancy, but it is a good idea to speak to your care team for advice first^[15]. It may be useful to find out if your partner is a carrier of thalassemia and discuss the effects with a genetic counselor. Some people with thalassemia need fertility treatment to help them get pregnant. During pregnancy there is an increased risk of problems, such as heart problems in the mother and growth problems in the baby^[15].

General Lifestyle

If the disease is fully compensated by ideal treatment, an individual with thalassemia major can enjoy a near-normal lifestyle and experience regular physical and emotional development from childhood to adulthood, including parenthood^[16].

To help reduce your chances of developing problems associated with thalassemia, it is a good idea to have a healthy, balanced diet, exercise regularly, avoid smoking and drinking excessive amounts of alcohol, and try to avoid infection by washing your hands with soap and water regularly and ensuring all your vaccinations are up to date^[15].

When you have thalassemia, healthy choices are particularly important. You should have the right to decide if, when, and with whom to talk about the disease^[16]. Genetic counseling can help you to understand your condition and its implications, including the risk to any future children you may have^[18].

Persons with the thalassemia trait have a normal life expectancy^[12].