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Test Catalog

Test ID: SCDT2    
Severe Combined Immunodeficiency Syndrome (SCID) Newborn Screening, Blood Spot

Useful For Suggests clinical disorders or settings where the test may be helpful

First-tier severe combined immunodeficiency syndrome (SCID) newborn screening

 

Second-tier testing of newborns with an abnormal screening result for SCID

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects severe combined immunodeficiency syndrome (SCID) by measuring T-cell receptor excision circle (TREC) levels in dried-blood spots.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Severe combined immunodeficiency syndrome (SCID) is a heterogeneous group of genetic conditions with severe T-cell lymphopenia. Infants with SCID are often asymptomatic at birth but are at risk for recurring infections within 4 to 6 months of age. In addition to T-cell lymphopenia, patients may also have B and/or NK cell lymphopenia, depending on the underlying genetic cause. Some cases of SCID may have additional features indicative of Omenn syndrome. Typical SCID carries a high rate of mortality (100%) within the first 2 years of life unless urgently treated. Early detection of SCID is critical to enable curative therapy or to institute a bridge therapy. Hematopoietic cell significantly transplant reduces morbidity and mortality and improves long-term survival.(1,2) There are at least 16 different molecular defects associated with the SCID phenotype including the leaky SCID/Omenn syndrome.(3) Omenn syndrome is associated with a hypomorphic mutation in a gene that causes SCID, along with additional features of erythrodermia, eosinophilia, adenopathy, hepatosplenomegaly, elevated IgE, oligoclonal T cell expansion of autologous cells, lack of maternal engraftment.

 

Newborn screening methods for SCID detect T-cell receptor excision circles (TRECs), which are nonreplicative, extrachromosomal DNA byproducts of T-cell receptor gene rearrangements.(2,3) TREC are typically expressed only in T cells of thymic origin, and are diluted by cell division.(2,4) The TREC used for measurement in this newborn screening method is the deltaRec-psiJalpha TREC and TREC analysis provides a sensitive assessment of thymic output. Low TREC values are indicative of either SCID or another clinical condition leading to severe T-cell lymphopenia.(5,6,7) In addition to typical SCID and leaky SCID, TREC newborn screening assays can detect up other secondary conditions, including syndromic disorders associated with T-cell lymphopenia, variant SCID (where the molecular diagnosis is unknown but the immunological and clinical criteria are indicative of SCID), and secondary T-cell lymphopenia due to other genetic conditions or prematurity.

 

When dried blood spot TREC quantitation is below normal range for age, additional immunological follow-up testing, such as TREC analysis in enriched cells (data expressed as TREC copies relative to patient's CD3+ T cell count) (TREC / T-Cell Receptor Excision Circles [TREC] Analysis, Blood), CD4 T-cell recent thymic emigrants (CD4RT / CD4 T-Cell Recent Thymic Emigrants [RTE]) and quantitative lymphocyte subsets: T, B, and NK by flow cytometry (TBBS / Quantitative Lymphocyte Subsets: T, B, and Natural Killer [NK]) are recommended. If any of these results are abnormal, recommendations for confirmation testing will be provided as needed.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Negative

Interpretation Provides information to assist in interpretation of the test results

Absolute T-cell receptor excision circles (TREC) concentration and an interpretive report are provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test may not detect all cases of T-cell lymphopenia.

 

Carrier status (heterozygosity) for severe combined immunodeficiency syndrome (SCID) or other T-cell lymphopenia cannot be detected.

 

T-cell receptor excision circles (TRECs) show an inverse correlation with age, and this test is not recommended for adults.

 

A positive test result may suggest a diagnosis of T-cell lymphopenia, related to SCID or another condition, but requires follow-up by additional testing, such as TREC analysis (data provided relative to patient's CD3+ T cell count) in enriched cells (TREC / T-Cell Receptor Excision Circles [TREC] Analysis, Blood), CD4 T-cell recent thymic emigrants (CD4RT / CD4 T-Cell Recent Thymic Emigrants [RTE]) and quantitative lymphocyte subsets: T, B, and NK, by flow cytometry (TBBS / Quantitative Lymphocyte Subsets: T, B, and Natural Killer [NK])

 

Premature infants are likely to have T-cell lymphopenia; therefore, if a patient is younger than 37 weeks gestational age, or 1500 g birth weight, repeat testing at the appropriate time is recommend.

 

Postanalytical interpretation of results may indicate improper storage and handling of the card, or that the patient received a blood transfusion prior to specimen collection, which may require a new specimen to repeat the analysis. Leuko-reduced, irradiated packed red blood cells, should not affect TREC analysis. Blood transfusions prior to specimen collection may lead to false-positive results (see above statement).

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. CLSI (2013): Newborn Blood Spot Screening for Severe Combined Immunodeficiency by Measurement of T-cell Receptor Excision Circles; Approved Guideline. CLSI document NBS06-A. Wayne, PA: Clinical and Laboratory Standards Institute

2. Sottini A, Ghidini C, Zanotti C, et al: Simultaneous Quantification of Recent Thymic T-cell and Bone Marrow B-cell Emigrants in Patients with Primary Immunodeficiency Undergone to Stem Cell Transplantation. Clin Immunol 2010, 136:217-227. doi: 10.1016/j.clim.2010.04.005. Epub 2010 May 10

3. Picard C, Al-Herz W, Bousfiha A., et al: Primary Immunodeficiency Diseases: An Update on the Classification from the IUIS Committee for Primary Immunodeficiency. J Clin Immunol 2015, Nov;35(8):696-726. doi: 10.1007/s10875-015-0201-1. Epub 2015 Oct 19

4. Van Zelm MC, Van der Burg M, Langerak AW, et al: PID Comes Full Circle: Applications of V(D)J Recombination Excision Circles in Research, Diagnostics and Newborn Screening of Primary Immunodeficiency Disorders. Front Immunol 2011, May 4;2:12. doi: 10.3389/fimmu.2011.00012. eCollection 2011

5. Kwan A, Abraham RS, Currier R, et al: Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States. JAMA, 2014;312(7):729-738. doi: 10.1001/jama.2014.9132

6. van der Spek J, Groenwold RH, van der Burg M, et al: TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. J Clin Immunol 2015 May, 35(4):416-430. doi: 10.1007/s10875-015-0152-6. Epub 2015 Apr 17

7. Vidal-Folch N, Milosevic D, Majumdar R, et al: A Droplet Digital PCR Method for Severe Combined Immunodeficiency Newborn Screening. J Mol Diagn 2017, Sep 19 (5): 755-765. doi: 10.1016/j.jmoldx.2017.05.011

Special Instructions Library of PDFs including pertinent information and forms related to the test