Thalassemias

Thalassemias are a group of blood disorders that affect the way the body makes hemoglobin, a protein found in red blood cells that is responsible for carrying oxygen throughout the body.

The body contains more red blood cells than any other type of cell, and each has a life span of about 4 months. Each day, the body produces new red blood cells to replace those that die or are lost from the body.

With a thalassemia, the red blood cells are destroyed at a faster rate, leading to anemia, a condition that can cause fatigue and other complications.

Thalassemias are inherited conditions — they're carried in the genes and passed on from parents to children. People who are carriers of a thalassemia gene show no thalassemia symptoms and might not know they're carriers. If both parents are carriers, they can pass the disease to their kids. Thalassemias are not contagious.

While there are many different types of thalassemias, the main two are:

1. Alpha thalassemia: when the body has a problem producing alpha globin
2. Beta thalassemia: when the body has a problem producing beta globin

When the gene that controls the production of either of these proteins is missing or mutated, it results in that type of thalassemia.

About Beta Thalassemia

Beta thalassemia occurs when the gene that controls the production of beta globin is defective. Beta thalassemia can be mild to severe and is more common in people of Mediterranean, African, and Southeast Asian descent.

A child can only get beta thalassemia by inheriting it from his or her parents. Genes are "building blocks" that play an important role in determining physical traits and many other things about us.

Humans are made up of trillions of cells that form the structure of our bodies and carry out specialized jobs like taking nutrients from food and turning them into energy. Red blood cells, which contain hemoglobin, deliver oxygen to all parts of the body.

All cells have a nucleus at their center, which is kind of like the brain or "command post" of the cell. The nucleus directs the cell, telling it to grow, mature, divide, or die. The nucleus contains DNA (deoxyribonucleic acid), a long, spiral-shaped molecule that stores the genes that determine hair color, eye color, whether or not a person is right- or left-handed, and many more traits. DNA, along with genes and the information they contain, is passed down from parents to their children during reproduction.

Each cell has many DNA molecules, but because cells are very small and DNA molecules are long, the DNA is packaged very tightly in each cell. These packages of DNA are called chromosomes, and each cell has 46 of them. Each package is arranged into 23 pairs — with one of each pair coming from the mother and one from the father. When someone has beta thalassemia, there is a mutation in chromosome 11.

Beta globin is made on chromosome 11 (beta globin, along with alpha globin, is one of the proteins that makes up hemoglobin). So, if one of the genes that tells chromosome 11 to produce beta globin is altered, less beta globin is made. This affects hemoglobin and decreases the ability of red blood cells to transport oxygen around the body.

Types of Beta Thalassemia

There are three types of beta thalassemia, depending upon whether one or two beta globin genes are mutated, and the severity of the mutations.

1. Beta thalassemia minor, or beta thalassemia trait, happens when one of the beta globin genes is mutated. People with this condition typically have very mild symptoms and require no treatment, but they can pass thalassemia on to their children. Usually, they are mildly anemic and their red blood cells are smaller than normal.
   
2. Beta thalassemia major (Cooley's anemia) happens when both of the beta globin genes are mutated. This is the most severe form of beta thalassemia. Babies with beta thalassemia major often seem healthy immediately after birth but start to develop symptoms within the first 2 years of life. This condition causes severe symptoms with life-threatening anemia that requires regular blood transfusions.
   
3. Beta thalassemia intermedia may also occur when both of the beta globin genes are mutated, but the mutations are less severe than those that typically cause beta thalassemia major. People with this condition usually have moderately severe anemia and sometimes require regular blood transfusions.

Complications

Beta thalassemia major and intermedia can lead to serious complications, especially if untreated. Complications of beta thalassemia major include:

• Excess iron. Kids who have beta thalassemia can end up with too much iron in their bodies, either from the disease itself or from getting repeated blood transfusions. Excess iron can cause damage to the heart, liver, and endocrine system.
• Bone deformities and broken bones. Beta thalassemia can cause bone marrow to expand, making bones wider, thinner, and more brittle. This makes bones more likely to break and can lead to abnormal bone structure, particularly in the bones of the face and skull.
• Enlarged spleen. The spleen helps fight off infections and filters out unwanted materials, such as dead or damaged blood cells, from the body. Beta thalassemia can cause red blood cells to die off at a faster rate, making the spleen work harder, which makes it grow larger. A large spleen can make anemia worse and may need to be removed if it gets too big.
• Infections. Children with beta thalassemia have a higher risk of infection, especially if they've had their spleens removed.
• Slower growth rates. The anemia resulting from beta thalassemia can cause children to grow more slowly and also can lead to delayed puberty.

Symptoms

The signs and symptoms of beta thalassemia vary depending on the type that a child has and how severe it is. Most children with beta thalassemia trait have no symptoms. Those with beta thalassemia major and intermedia may not show any symptoms at birth, but usually develop them in the first 2 years of life.

Some of the more common symptoms of beta thalassemia include:

• fatigue, weakness, or shortness of breath
• a pale appearance or a yellow color to the skin (jaundice)
• irritability
• deformities of the facial bones
• slow growth
• a swollen abdomen
• dark urine

Babies who begin to show symptoms of beta thalassemia after a few healthy months may fail to grow normally (failure to thrive); have trouble feeding; and have episodes of fever, diarrhea, and other intestinal problems.

Diagnosis

In most cases, beta thalassemia is diagnosed before a child's second birthday. Children with beta thalassemia major may have a swollen abdomen or symptoms of anemia or failure to thrive.

If the doctor suspects beta thalassemia, he or she will take a blood sample for testing. Blood tests can reveal red blood cells that are pale, varied in shape and size, or smaller than normal. They also can detect low red blood cell counts and cells with an uneven distribution of hemoglobin, which causes them to look like a bull's-eye when seen through a microscope.

Blood tests also can measure the amount of iron in the blood, evaluate hemoglobin, and test a child's DNA for abnormal hemoglobin genes.

If both parents are carriers of the beta thalassemia disorder, doctors can conduct tests on a fetus before birth. This is done through either:

• chorionic vilius sampling, which takes place about 11 weeks into pregnancy and involves removing a tiny piece of the placenta for testing
• amniocentesis, which is usually done about 16 weeks into the pregnancy and involves removing a sample of the fluid that surrounds the fetus

If one parent carries a beta thalassemia gene and the other carries a different gene that also affects beta globin, such as a sickle gene, their child could have a significant blood disorder. Therefore, people who carry beta thalassemia genes should seek genetic counseling if they're considering having children.

Treatment

The amount of treatment that beta thalassemia requires depends on how severe the symptoms are. For most children with beta thalassemia trait, whose only symptom may be mild anemia from time to time, no medical treatment will be necessary.

However, the blood counts in beta thalassemia trait look a lot like the blood counts in iron deficiency anemia, which is a very common disorder. It's important for doctors to know when children have beta thalassemia trait so that they do not treat them with iron if it's not needed.

Doctors also might recommend a folic acid supplement for kids with moderate cases of anemia to help boost production of new red blood cells.

Some children with moderate anemia may require an occasional blood transfusion, particularly after surgery. Those with severe cases of beta thalassemia major, on the other hand, may require regular blood transfusions their entire lives to keep them healthy. During blood transfusions, they're given blood from donors with matching blood types. Over time, this can cause a build-up of iron in the body, so kids who receive frequent blood transfusions may have to take medications to remove excess iron from their bodies.

Research into treating beta thalassemia with experimental gene therapies is ongoing, but for now it can only be cured by a procedure called a bone marrow transplant. Bone marrow, which is found inside bones, produces blood cells. In a bone marrow transplant, children are first given high doses of radiation or drugs to destroy the defective bone marrow. The bone marrow is then replaced with cells from a compatible donor, usually a healthy sibling or other relative. Bone marrow transplants carry many risks, so they usually are done only in the most severe cases of thalassemia.

If your child has beta thalassemia, support groups are available to help your family cope with the obstacles presented by the disease.

Reviewed by: Robin Miller, MD
Date reviewed: February 2012