SCID Screening

Severe Combined Immunodeficiency, or SCID, causes major abnormalities of the immune system, leaving newborns unable to fight infections effectively.

Even mild infections can become life-threatening, and newborn screening is often the only way to identify SCID before serious complications arise. Early detection through newborn screening enables early treatment to prevent life-threatening consequences.

Severe Combined
Immunodeficiency

Severe Combined Immunodeficiency, or SCID, is the name of a group of rare, inherited disorders caused by mutations in genes essential for the development of infection-fighting immune cells.

Understand SCID

The first symptoms of SCID typically appear when the baby is a few months old. Due to the wide range of symptoms, diagnosis is often delayed, and by the time the disease is confirmed, the infant’s health may already be severely compromised.

Without a known family history of SCID, neonatal screening is the only reliable way to detect the condition early, allowing for timely intervention before life-threatening infections and complications develop.

Causes of SCID

SCID form part of a larger group of conditions known as primary immunodeficiencies and is caused by mutations in different genes involved in development of different types of immune cells, or lymphocytes; T-cells, B-cells and natural killer (NK) cells. These three types of lymphocytes play crucial roles in the immune defence and their absence severely compromises the new-born’s ability to fight infections.

Most patients with SCID have absent T-cells and may also have deficiencies in B-cells and/or natural killer (NK) cells.

Types of SCID

There are many different types of SCID, each classified by the specific gene mutation responsible for the condition. Defects in more than 20 genes have been identified as causes of SCID, and the list of implicated genes continues to grow.

The most common type of SCID is X-linked SCID, caused by mutations in the IL2RG gene, which encodes the common gamma chain. Other examples of the major types of SCID include Adenosine Deaminase Deficiency SCID (ADA-SCID), RAG1/RAG2 Deficiency (Omenn Syndrome), Janus Kinase 3 Deficiency (JAK3-SCID), and more.

SCID Prevalence

SCID prevalence varies between geographical locations and ethnic backgrounds, but the overall prevalence for SCID is estimated to be in 1 to 50,000 live births.

Markers for SCID

Early detection of SCID through newborn screening is based on the detection of T-cell receptor excision circle (TREC). TRECs are a circular DNA fragments formed at the early stage of the maturation process of T-cells and is a by-product formed during genomic recombination of the T-cell receptor. They are excised from the genomic DNA, and therefore do not undergo further replication during cell division but remain as episomal residues in the cell.

The number of TREC copies in healthy newborns is high due to the high rate of newly formed T-cells. Newborns with immunodeficiencies, including SCID, however typically display a significant reduction or complete absence of TREC copies, making quantification of TRECs a suitable marker for SCID.

Treatment for SCID

Infants with SCID are highly vulnerable to infections. Screening enables preventive measures, such as isolation from sick individuals, prophylactic antibiotics, and avoidance of live vaccines, all of which protect the child from infections while awaiting treatment.

Treatment options for SCID focus on restoring the immune function and can vary depending on the type of SCID. Allogeneic hematopoietic Stem Cell Transplant (HSCT) reconstitutes a functional immune system by infusion of donor stem cells and has been the gold standard for the treatment of SCID ever since the first stem cell transplantation in 1968.

Without treatment, the infant is likely to die within the first years of life, but with prompts treatment, the chances of survival are 95-100%.

Early diagnosis of SCID leads to earlier treatment, significantly improving survival rates.

Without treatment, infants with SCID often die from infections within the first year of life.

Benefits

Implementation of SCID Screening in NBS programs

Early intervention and treatment

Without screening, SCID is often diagnosed only after serious infections occur, which can be life-threatening. Early diagnosis leads to earlier treatment, significantly increasing survival rates and preventing complications, which reduces the need for long-term hospitalization and intensive care. Late diagnosis may also reduce the effectiveness of treatment.

Reduced complications and prevention of severe infections

Knowing the diagnosis allows healthcare providers to tailor care (e.g., isolation from sick individuals) and avoid procedures that could be risky for a child with SCID (such as administering live vaccines).

Comprehensive screening

Comprehensive screening through early detection and intervention significantly reduces morbidity and mortality rates. The newborn blood spot test is a non-invasive and highly effective method that allows to identify life-threatening genetic disorders such as Spinal Muscular Atrophy (SMA) and SCID early on, vastly improving long-term health outcomes.