Newborn Screening for SCID Identifies Patients with Ataxia Telangiectasia

Mallott, Jacob; Kwan, Antonia; Church, Joseph A.; González-Espinosa, Diana; Lorey, Fred; Tang, Ling; Sunderam, Uma; Rana, Sadhna; Srinivasan, R.; Brenner, Steven E.; Puck, Jennifer M.

doi:10.1007/s10875-012-9846-1

Cited by 85 publications

(59 citation statements)

References 40 publications

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“…In the most frequent one in TCL group, syndromes, the foremost cause is DiGeorge syndrome [17]. Down syndrome is also one of the frequent reasons of low TRECs, with others including CHARGE syndrome, cartilage hair hypoplasia, Nijmegen breakage syndrome, ataxia telangiectasia, Fryns syndrome, Jacobsen syndrome; VACTERL association; TAR syndrome; ectrodactyly ectodermal dysplasia syndrome [18]; as well as non-immune disorders e.g. chylous effusions making T-cells vanished [19].…”

Section: Immunologic Disorders Beyond Scid Detected By Trec Testmentioning

confidence: 99%

“…ADA deficiency is a common cause of SCID and late-onset ADA deficiency can be overlooked by the TREC assay [25]. TREC screening detects less than 50% of cases of ataxia telangiectasia [26]. Several rare disorders, such as Ora1, Stim1, or CD40 ligand deficiency, show an infectious phenotype similar to SCID but have normal numbers of T cells, and it is unknown whether the TREC assay can detect these disorders [27,28].…”

Section: Limitations Of the Trec For Neonatal Screening Programsmentioning

confidence: 99%

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Neonatal Screening Test for Severe Combined Immunodeficiency of Primary Immunodeficiency Diseases: TREC Assay and Its Limitations

Özdemir¹

2016

MOJI

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The expansion of a different inventory of T cells, with their individual T cell receptor (TCR), is crucial for identification of unknown antigens attached to self MHC molecules. To produce many exclusive TCRs, DNA gene reorganization and linear reassembly is executed in thymocytes, in order that each cell has its particular mixture of a TCR variable (V), diversity (D) and joining (J) series. The cut out DNA remains of the TCR are also bound at their ends, making various rounded DNA byproducts called as TRECs [10,11]. TRECs, circular byproducts of TCR V(D) J recombination, function as an indicator for recently produced naïve T cells. TRECs are constant, but are not multiplied during AbstractThe aim of any screening program in the newborn is the early detection of treatable genetic disorders having a high velocity of morbidity and mortality. T-cell receptor excision circle (TREC), circular byproducts of T-cell receptor V (D) J recombination, function as an indicator for recently produced naïve T cells. Wellknown genetic defects resulting in severe combined immunodeficiency (SCID) detected by the TREC assay are as following: IL-7 receptor; ADA; IL-2 receptor ɣ chain; etc. Other than SCID and leaky SCID patients, less important subjects of TREC assay contain infants with non-SCID T-cell lymphopenia. In this group, most frequent ones are syndromes such as DiGeorge, Down, Nijmegen breakage syndrome, ataxia telangiectasia, etc. Although the TREC assay can identify many types of T-cell lymphopenia, it may not be a screening test for every primary immunodeficiency disease. There is a group of combined immunodeficiencies in which lymphopenia is not a finding, but the immune dysfunction is as severe as in typical SCID patients. For instance; chronic granulomatous disease, congenital neutropenia, toll-like receptor defects, ZAP-70 and MHC class II deficiency that may be missed by this assay. Recent reports also confirm that TREC assay is not effective in identifying a subset of rare but deadly immunodeficiencies. Therefore, it is vital that any infant with unusual or serious infections be assessed by an expert clinical immunologist.

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Section: Immunologic Disorders Beyond Scid Detected By Trec Testmentioning

confidence: 99%

Section: Limitations Of the Trec For Neonatal Screening Programsmentioning

confidence: 99%

Neonatal Screening Test for Severe Combined Immunodeficiency of Primary Immunodeficiency Diseases: TREC Assay and Its Limitations

Özdemir¹

2016

MOJI

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“…Exome Sequencing and Analysis WES was performed as previously described [5]. Briefly, libraries prepared by ligating TruSeq adaptors (Illumina: San Diego, CA) to genomic DNA fragments of 200-300 bp were enriched with 10 cycles of PCR, pooled and submitted to exon capture using a Roche Nimblegen version 3.0 capture array.…”

Section: Subjects and Samplesmentioning

confidence: 99%

“…88 (4) 26 (2) 72 (5) 174 (10) 104-1448 745-3499 858-3774 CD3-CD16/56+ NK cells /mm3 (%) 638 (29) 680 (66) 1123 (73) 1169 (68) 60-434 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) 194-994 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) 182-1581 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) IgG (mg/dL) [ Hercules, CA) and incubated with antibodies to nibrin (Novus, NB100-143 at 1:5000, Littleton, CO) overnight at 4°C. The immunoblots were subsequently incubated with an HRP-conjugated anti-rabbit secondary antibody at room temperature for 40 min for detection by enhanced chemiluminescence (ECL) (Amersham Pharmacia, Piscataway, NJ).…”

Section: Immunoblottingmentioning

confidence: 99%

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Nijmegen Breakage Syndrome Detected By Newborn Screening for T Cell Receptor Excision Circles (TRECs)

Patel

Puck

Kundu³

et al. 2015

Journal of Allergy and Clinical Immunology

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Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

Kwan

Abraham

Currier

et al. 2014

JAMA

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IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

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Newborn Screening for SCID Identifies Patients with Ataxia Telangiectasia

Cited by 85 publications

References 40 publications

Neonatal Screening Test for Severe Combined Immunodeficiency of Primary Immunodeficiency Diseases: TREC Assay and Its Limitations

Neonatal Screening Test for Severe Combined Immunodeficiency of Primary Immunodeficiency Diseases: TREC Assay and Its Limitations

Nijmegen Breakage Syndrome Detected By Newborn Screening for T Cell Receptor Excision Circles (TRECs)

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

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