Pediatric Thalassemia and Your Child

In thalassemia, you inherit changes in the genes responsible for building hemoglobin, the main oxygen-carrying part of your red blood cells.

There are two main types of thalassemia: alpha-thalassemia and beta-thalassemia.

Most healthy hemoglobin includes two proteins: alpha-globin and two beta-globin. Inheriting faulty alpha-globin genes causes alpha-thalassemia. Likewise, inheriting faulty beta-globin genes results in beta-thalassemia.

The altered hemoglobin made by these faulty globin genes makes red blood cells small, fragile, and ineffective. These ineffective red blood cells cause microcytic anemia and other conditions.

Pediatric thalassemia symptoms are lifelong. In more severe forms of alpha- and beta-thalassemia, symptoms are usually present by 2 years old.

The most common issue of pediatric thalassemia is microcytic anemia, which is low hemoglobin with small red blood cells. Depending on the type of thalassemia you have, anemia can range from mild to severe.

Anemia can cause symptoms in children like:

• pale skin, cheeks, and lips
• irritability
• fatigue
• napping more often

Children with severe forms of thalassemia can have more serious anemia, hemolysis, and iron overload, often from repeated blood transfusions.

As their bodies urgently try to produce more red blood cells, other organs other than the bone marrow may be affected. This can lead to symptoms like:

• slowed growth and delayed development
• bone problems, including thinning and distorted bones
• enlarged liver and spleen
• dark brown urine
• shortness of breath
• gallstones
• heart disease, including cardiomyopathy and arrhythmia
• peripheral neuropathy

Thalassemia is inherited. In an autosomal-recessive pattern, children inherit the genes responsible for building healthy hemoglobin from their parents.

The genes involved in causing thalassemia include:

Alpha-globin genes

People have four alpha-globin genes located on chromosome 16. More than 130 possible changes to these genes are associated with alpha-thalassemia.

There are several types of alpha-thalassemia, including:

Alpha-thalassemia trait

If a child inherits one or two faulty alpha-globin genes, they have alpha-thalassemia trait, also called alpha-thalassemia minima/silent carrier or alpha-thalassemia minor.

This type may cause mild anemia with small red blood cells. But because their body can still make enough healthy hemoglobin, alpha-thalassemia trait usually won’t cause any symptoms.

Alpha-thalassemia disease

Inheriting three faulty alpha-globin genes causes more significant problems. This is called alpha-thalassemia disease or hemoglobin H disease.

Depending on the type of gene mutations a child inherits, symptoms can range from mild to severe.

Hemoglobin Barts disease

Sometimes, a fetus may inherit problems with all four alpha globin genes. This extremely severe form of alpha-thalassemia disease is called hemoglobin Barts disease. It causes severe hydrops fetalis and is often fatal before birth.

Beta-globin gene

This gene is located on chromosome 11. More than 200 mutations in it are associated with beta-thalassemia.

There are several types of beta-thalassemia, including:

Beta-thalassemia trait

If a child inherits problems with one of two beta-globin genes, they’ll have the beta-thalassemia trait. This causes mild anemia with small red blood cells. But they still have one functional beta-globin gene and plenty of healthy hemoglobin, so their anemia is typically asymptomatic.

Beta-thalassemia disease

In this case, both of the beta-globin genes are mutated. Depending on the type of mutation a child inherits, they might develop beta-thalassemia intermedia with fewer symptoms when at least one of their beta-globin genes can still make a reduced amount of normal beta-globin.

They may also develop beta-thalassemia major or Cooley anemia if their body is unable to make any healthy beta-globin. Symptoms of Cooley anemia start early in life and are very serious, requiring repeated blood transfusions.

Thalassemia is an inherited disease. Having a family history of thalassemia trait or disease is a significant risk factor.

Thalassemia is more common in Mediterranean, Asian, Middle Eastern, and African populations. If you have anemia and your heritage is from these regions, your doctor might order blood tests for thalassemia.

There are several tests a doctor may use to diagnose pediatric thalassemia, including:

• Newborn blood screen: Some forms of thalassemia disease may be detected prenatally or seen on newborn blood screening.
• Physical exam: Doctors may suspect pediatric thalassemia disease in a young child with anemia, jaundice, and an enlarged liver.
• Complete blood count (CBC): The first test usually ordered is a CBC, which often shows anemia with small red blood cells.
• Other blood tests: Doctors may also order other blood tests, such as hemoglobin electrophoresis or thalassemia gene testing.

Mild forms of thalassemia, such as thalassemia trait, often don’t require treatment. For children with more serious forms of thalassemia disease, a specialist called a pediatric hematologist supervises treatment.

Treatment may include:

• Medications:
  • folic acid, which supports red blood cell production
  • luspatercept (Reblozyl), which stimulates your body’s red blood cell production
  • iron chelation, which removes excess iron resulting from chronic blood transfusions
• Blood transfusions:
  • Blood transfusions may be needed as often as every few weeks for severe or symptomatic anemia, usually due to beta-thalassemia major.
• Surgery:
  • Splenectomy can reduce the need for transfusions. But people without a spleen may also require extra immunizations and daily antibiotics to help prevent infections.
  • Gallbladder removal may be helpful for thalassemia-triggered gallstones.
• Gene therapy: Gene therapy transfers healthy copies of the affected genes and other genetic material, such as betibeglogene autotemce (Zynteglo), which is mixed with a child’s own blood stem cells.
• Stem cell transplant: Stem cell transplants can cure some types of thalassemia. However, it can be difficult to find a matched donor, and stem cell transplants may lead to other health complications. During stem cell transplant, healthy blood-producing cells are infused into the bone marrow to help the body produce more healthy red blood cells and replace the abnormal ones.

Children with thalassemia trait or thalassemia minor are unlikely to develop significant symptoms or require treatment. The thalassemia trait does not develop into thalassemia disease.

Children with thalassemia disease need lifelong care from a hematologist. Treatment can help manage their anemia, ineffective red blood cell production, and any complications.

The outlook for children with thalassemia has significantly improved over recent decades. Advances in the monitoring and treatment of iron overload, along with newer gene therapies, can manage symptoms and lengthen the life span of people with transfusion-dependent thalassemia disease.

Thalassemias are a common group of inherited blood disorders. People are born with the condition.

Thalassemia trait, also called thalassemia minor, rarely causes significant health problems. But children with alpha- or beta-thalassemia disease may experience anemia and problems with the bones and organs.

Symptoms of pediatric thalassemia usually develop in infancy or young childhood. In the most severe forms, frequent blood transfusions may be necessary.

If your child has thalassemia, an experienced pediatric hematologist can help. Therapy is available to monitor for, prevent, and treat some of the most serious complications of thalassemia disease.