What Causes Beta Thalassemia?

What Exactly Happens in the Body with Beta Thalassemia?

To understand what causes beta thalassemia, you need to know a little about hemoglobin. Hemoglobin has two main parts: alpha-globin and beta-globin. In a healthy person, the body makes roughly equal amounts of both. In beta thalassemia, the beta-globin production is low or absent.

Without enough beta-globin, the alpha-globin builds up inside red blood cells. This excess alpha-globin damages the cell membranes. The cells die early, and the bone marrow cannot keep up with demand. The result is chronic anemia. The body tries to compensate by making more red blood cells, but they are often misshapen and fragile. This process is what causes the symptoms like fatigue, pale skin, and slowed growth in children.

There are two main types of beta thalassemia based on how severe the mutation is. Beta thalassemia major means the body makes very little to no beta-globin. Beta thalassemia intermedia means the body makes some beta-globin, enough to avoid the need for regular blood transfusions but still cause significant anemia.

How Do You Inherit the Gene Mutations That Cause Beta Thalassemia?

The genetics are straightforward but often misunderstood. The HBB gene sits on chromosome 11. Every person has two copies of this gene. One comes from your mother. One comes from your father.

If both copies have a mutation, you have beta thalassemia. If only one copy has a mutation, you are a carrier. Carriers are sometimes said to have beta thalassemia minor or thalassemia trait. They usually have mild or no symptoms. They may have slightly smaller red blood cells than normal, but they do not need treatment.

The risk for children depends on the parents’ carrier status. If both parents are carriers, each child has a 25% chance of having beta thalassemia major, a 50% chance of being a carrier, and a 25% chance of having two normal genes. If one parent has beta thalassemia and the other is a carrier, the risk changes. The CDC provides clear guidance on these inheritance patterns for family planning.

What Are the Specific Gene Mutations That Cause Beta Thalassemia?

There are over 300 different mutations in the HBB gene that can cause beta thalassemia. The specific mutation determines how severe the disease will be. Some mutations completely stop beta-globin production. These are called beta-zero mutations. Others reduce production but do not stop it entirely. These are called beta-plus mutations.

The most common mutations vary by population. For example, people of Mediterranean descent, such as those from Italy, Greece, or Cyprus, often have specific mutations like IVS-I-110 or IVS-I-6. People of Southeast Asian descent, including those from Thailand, Vietnam, or China, have different common mutations like codon 41/42 or IVS-II-654.

Research published in the journal Blood has mapped out the global distribution of these mutations. This is important because it helps doctors predict the course of the disease. A child with a beta-zero mutation from both parents will likely have severe disease requiring lifelong transfusions. A child with two beta-plus mutations may have a milder form.

Is Beta Thalassemia the Same as Sickle Cell Disease?

No, but they are related. Both are genetic disorders of the beta-globin gene. Sickle cell disease is caused by a specific mutation that changes the shape of hemoglobin. Beta thalassemia is caused by mutations that reduce the amount of hemoglobin.

However, a person can inherit a beta thalassemia mutation from one parent and a sickle cell mutation from the other. This condition is called sickle-beta thalassemia. It has features of both diseases. The severity depends on which specific mutations are involved. Some people with sickle-beta thalassemia have mild symptoms. Others have severe pain crises and organ damage similar to sickle cell disease.

This is a good example of why genetic testing and counseling are so important. Knowing your specific mutations helps doctors plan the right care.

Can Beta Thalassemia Be Prevented or Avoided?

You cannot prevent the genetic mutation itself. It is in your DNA from conception. But you can make informed choices about having children if you know your carrier status.

Screening is straightforward. A simple blood test called a complete blood count (CBC) can show if your red blood cells are smaller than normal. This is the first clue. A follow-up test called hemoglobin electrophoresis can confirm if you carry a beta thalassemia mutation.

The American College of Obstetricians and Gynecologists recommends carrier screening for people with a family history of thalassemia or those from high-risk ethnic groups. If both partners are carriers, they can meet with a genetic counselor. Options include prenatal testing, preimplantation genetic diagnosis with IVF, or using donor eggs or sperm.

These are personal decisions. The goal here is not to tell you what to do. It is to give you the facts so you can make your own choice.

What Are the Common Misconceptions About What Causes Beta Thalassemia?

There are several myths about this condition that need clearing up.

One common myth is that beta thalassemia is caused by poor diet or iron deficiency. This is false. You cannot develop beta thalassemia from eating poorly or lacking iron. It is a genetic condition present from birth. However, iron deficiency anemia can look similar on a blood test. This is why doctors must do specific hemoglobin testing to tell them apart.

Another myth is that beta thalassemia is contagious. It is not. You cannot catch it from another person. You cannot get it from a blood transfusion. You can only inherit it from your parents.

A third misconception is that beta thalassemia only affects certain races. While it is more common in people of Mediterranean, Middle Eastern, South Asian, and Southeast Asian descent, it can affect anyone. The gene mutation can appear in any population, though it is rarer in people of Northern European descent.

What Treatments Are Available for People With Beta Thalassemia?

Treatment depends entirely on the severity. People with beta thalassemia major need regular blood transfusions, usually every 2 to 4 weeks, to keep their hemoglobin levels high enough for normal growth and activity.

The problem with frequent transfusions is iron overload. Your body has no natural way to remove excess iron from blood transfusions. Over time, iron builds up in the heart, liver, and pancreas. This can cause serious organ damage. To manage this, patients take iron chelation therapy. These are medications that bind to excess iron so the body can excrete it. Common chelators include deferasirox (Exjade or Jadenu) and deferoxamine (Desferal).

For beta thalassemia intermedia, treatment is less intensive. Some people need transfusions only during illness, pregnancy, or surgery. Others may benefit from a medication called luspatercept (Reblozyl), which helps the body make more red blood cells. Folic acid supplements are also commonly recommended.

The only curative treatment is a bone marrow or stem cell transplant from a matched donor. This procedure carries serious risks, including graft-versus-host disease and infection. It is typically reserved for children with severe disease who have a good donor match. Gene therapy is an emerging option. In 2022, the FDA approved a gene therapy called betibeglogene autotemcel (Zynteglo) for people with beta thalassemia who need regular transfusions. It is expensive and not widely available, but it offers the possibility of a cure without a donor.