Severe Combined Immunodeficiences Screening -Infant

Severe Combined Immunodeficiences Screening -Infant

Severe Combined Immunodeficiences Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The congenital screening for Congenital adrenal hyperplasia  is recommended.

B

OVERVIEW

Severe combined immunodeficiency (SCID) includes a group of rare, but serious and potentially fatal inherited immune disorders in which T lymphocytes fail to develop and B lymphocytes either are absent or compromised. Impairment of both B and T cells leads to the term “combined.” Untreated patients develop life-threatening infections. The screening test for TRECs, a byproduct of normal T-cell development, identifies SCID and some related conditions with low T cells that result in less severe immunodeficiency. Some infants with mild to moderately low TRECs have a transient lymphopenic condition related to delay in maturation of the immune system, which can be more common in the neonatal intensive care unit /premature infant population.

SCREENING

Finding

Absent or severely reduced T-cell receptor excision circles (TRECs), which are produced during normal T-cell maturation

Tested By

TREC test; PCR-based assay that detects the number of TRECs

PREVALENCE

Prevalence is approximately 1:58,000. 

INHERITANCE

SCID is inherited in an autosomal recessive manner. It affects both boys and girls equally.

MATERNAL & FAMILY HISTORY

About 1/3 of children with SCID may have a family history of infant death due to infection or known SCID. 

PRENATAL TESTING

Prenatal testing involves DNA testing or enzyme analysis by amniocentesis or chorionic villus sampling (CVS). It is only recommended if there is a family history of SCID.

CLINICAL CHARACTERISTICS

Babies with SCID are at high risk for life-threatening infections that can begin as early as 1 month after birth. Without treatment, individuals suffer from frequent or severe infections that result in rashes, diarrhea, increasing illness, complications, and even death within the first 1 or 2 years of life. 

Depending on the type of SCID, treatment modalities include hematopoietic transplant (bone marrow or stem cell), gene therapy (currently an investigational treatment in the United States), or enzyme replacement (for adenosine deaminase deficiency SCID). Infants who receive hematopoietic transplant to reconstitute the immune system prior to 3.5 months of age have a >95% chance of survival. Transplantation survival decreases to less than 80% after 3.5 months of age, usually because of complications resulting from infections. 

Early signs of SCID include:

  • Frequent, severe infections caused by common bacteria, viruses, or opportunistic infections, such as Pneumocystis jirovecii
  • Infections that do not respond appropriately to antibiotic treatment
  • Diarrhea
  • Poor weight gain or growth (failure to thrive)
  • Persistent thrush (candidiasis, a fungal infection) in the mouth or throat
  • Infections from live viral vaccines (rotavirus, MMR, and varicella vaccines)
  • Severe eczematous rash from birth that does not respond to treatment

EARLY SIGNS

Babies with severe combined immunodeficiency (SCID) are more likely to develop life-threatening infections.  This is why early screening and identification are so important.

Early signs of SCID include:

  • High number of infections
  • Infections that do not improve with antibiotic treatment for two or more months
  • Diarrhea
  • Poor weight gain or growth (failure to thrive)
  • Thrush (a fungal infection) in the mouth or throat that does not go away

If your baby shows any of these signs, be sure to contact your baby’s doctor immediately.

CAUSES

Our immune systems are made up of special cells and proteins that protect us from germs and other things in our environment that can cause illnesses and infections. Specifically, T-cells and B-cells are types of white blood cells that are very important to our immune system.

If your baby has severe combined immunodeficiency (SCID), then his or her body either does not make enough or makes non-working T and B-cells. Without these working cells, the immune system cannot work correctly. This is why infants with SCID are more likely to catch serious infections and illnesses.

There are many different genetic causes of SCID. SCID may be inherited from parents or can be the result of a new genetic change in the child.  All known forms of SCID follow either an autosomal recessive or an X-linked recessive pattern of inheritance.

When SCID is an autosomal recessive genetic condition, a child must inherit two copies of the non-working gene, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with SCID is rare, when both parents are carriers, they can have more than one child with the condition. 

When SCID is an X-linked recessive genetic condition, a male must inherit one copy of the non-working gene from his mother to have the condition. A female must inherit two copies of the non-working gene, one from each parent, in order to have the condition. In X-linked conditions, the gene is carried on the X sex chromosome; therefore, the condition affects males more than females. While having a child with SCID is rare, when one or both parents carry the non-working gene, they can have more than one child with the condition.

TREATMENT

Isolation

Your baby may need to stay away from young children. This makes it less likely he or she will catch an illness from another child.

Immunoglobulin Replacement Therapy

Babies with SCID should be placed on immunoglobulin replacement therapy if they are more than three months of age or have already had infections. Regular immunoglobulin replacement therapy can replace missing antibodies that help your baby fight infections.

Bone Marrow Transplant

The most effective treatment for SCID is a bone marrow transplant. Bone marrow makes cells for fighting infections and illnesses. In a bone marrow transplant, bone marrow cells from a person with a working immune system are given to a person with SCID, whose bone marrow cannot make cells to fight infections and illnesses.

EXPECTED OUTCOMES

With early screening and treatment, babies with severe combined immunodeficiency (SCID) are less likely to develop life-threatening illnesses and infections. Children who receive bone marrow transplants often lead healthy lives.

If left untreated, babies with SCID can develop serious and fatal infections. Children with SCID who do not receive early treatment rarely live past two years of age.