T-cell related lymphocyte deficiencies are a group of inherited (genetic) conditions where a baby is born with a decreased immune system.

The immune system fights infections. The immune system uses special white blood cells called lymphocytes to fight against germs that invade the body. Lymphocytes include T cells, B cells, and natural killer (NK) cells.

Babies with T-cell related lymphocyte deficiencies, either do not have T cells, have a decreased number of T cells, or have T cells that do not work normally. There are several types of T-cell related lymphocyte deficiencies, including 22q11.2 deletion syndrome and ataxia-telangiectasia. All types have low and/or abnormal T-cells but the different types may affect different parts of the body. When the cause of the T-cell deficiency is unknown, the condition is called idiopathic T-cell lymphopenia.

If the immune system is weak, your baby’s body has trouble fighting infections. They can get sick from germs that do not infect people with working immune systems, leading to the signs and symptoms of the condition. Without treatment and special protection from germs, T-cell related lymphocyte deficiencies can lead to life-threatening illness or death.

• It is estimated that approximately 1000 babies are born with the most common form of this condition, 22q11.2 deletion syndrome, each year in the United States.
• It is estimated that fewer than 100 babies are born with another form of this condition, ataxia-telangiectasia, each year in the United States.

There are many different genetic causes of T-cell related lymphocyte deficiency. Some types that may be found by newborn screening are:

• 22q11.2 deletion syndrome, including DiGeorge syndrome (DGS)
• Ataxia-telangiectasia
• Idiopathic T-cell lymphopenia (no specific cause is found for the low or nonworking T cells)

In nearly all cases, the T-cell related lymphocyte deficiency is caused when one of several genes that give the body instructions for making parts of the immune system does not work. The parts of the immune system called T cells, which are a type of white blood cell, are decreased. Without these cells, the body cannot fight infections.

T-cell related lymphocyte deficiencies are genetic conditions. In some cases (like 22q11.2 deletion syndrome), a baby may spontaneously develop a genetic change, which is not inherited from either parent. In other cases, babies inherit a genetic change from their biological (birth) parents.

• Some types of T-cell lymphocyte deficiency are inherited in an X-linked recessive pattern, which means babies inherit this condition on their X chromosome.
  • Girl babies have two X chromosomes, so only girls with two nonworking genes have T-cell lymphocyte deficiency. Girls with one nonworking gene are carriers.
  • Boy babies only have one X chromosome, so boys with only one nonworking gene have T-cell lymphocyte deficiency. This condition is more common in boys.
• Other types of T-cell lymphocyte deficiency (like ataxia telangiectasia) are autosomal recessive conditions. Babies inherit the condition when each parent passes down a nonworking gene to their baby. Only babies with two nonworking genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the gene are called carriers.
  • Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
  • If two parents are carriers of a nonworking copy of the gene, they have a 1 in 4 chance of having a child with T-cell lymphocyte deficiency.
  • Carriers for T-cell lymphocyte deficiency often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with T-cell lymphocyte deficiency.
  • Parents who already have a child with T-cell lymphocyte deficiency still have a 1 in 4 chance of having another child with T-cell lymphocyte deficiency. This 1 in 4 chance stays the same for all future children.
• Around 10% of the time, the 22q11.2 deletion syndrome type of T-cell lymphocyte deficiency can be inherited in an autosomal dominant pattern. In this case, at least one of the parents also has 22q11.2 deletion syndrome. Babies inherit the condition when the parent with 22q11.2 deletion syndrome passes down their nonworking gene to their baby. Babies with just one nonworking gene—one from the mom or one from the dad—have this condition.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

Signs of T-cell related lymphocyte deficiencies usually appear in the first few months after birth and may include the following:

• Infections that do not get better with antibiotic treatment
• Diarrhea
• Creamy white dots in the mouth or throat that do not get better (thrush)
• Poor weight gain or growth (failure to thrive)

In addition, based on the specific cause of the T-cell related lymphocyte deficiency, there may be other parts of the body affected. These can include:

• Heart problems
• Low calcium in the blood
• Cleft palate
• Skin problems
• Problems with the blood vessels

Newborn screening for T-cell related lymphocyte deficiencies is done using a small amount of blood collected from your baby’s heel.

During screening, a special machine measures how many small pieces of DNA (called T cell receptor excision circles or TRECs) are in your baby’s blood. The body produces TRECs when it is developing the T cells of the immune system. Babies without an immune system, or one that does not work as it should, have little or no TRECs. These babies might have a T-cell related lymphocyte deficiency.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for T-cell related lymphocyte deficiencies is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has a T-cell related lymphocyte deficiency. It does mean that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood tests
• Genetic tests using a blood sample

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition do occur. Screening samples collected from babies who were born early (premature) or very sick (in the newborn intensive care unit, or NICU) for other reasons can have false-positive results. This screening can also pick up other conditions that affect the immune system.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.

It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.

Treatments may include the following:

• Isolation (avoiding infections/germs)
• Antibody treatment (also called immunoglobulin replacement therapy)
• Bone marrow or thymus transplant to help grow and replace an immune system
• Careful timing and monitoring of certain types of vaccinations

Children who receive early and ongoing treatment for T-cell lymphocyte deficiency are less likely to have life-threatening infections and illnesses. Children who receive bone marrow or thymus transplants can lead healthy lives.