Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Borte, Stephan; Döbeln, Ulrika von; Fasth, Anders; Wang, Ning; Janzi, Magdalena; Winiarski, Jacek; Sack, Ulrich; Pan‐Hammarström, Qiang; Borte, Michael; Hammarström, Lennart

doi:10.1182/blood-2011-08-371021

Cited by 174 publications

(229 citation statements)

References 20 publications

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“…The TREC/KREC assay was performed as described previously, [12,13]. Briefly, DNA was extracted from single 3.2 mm diameter punches of the DBS in 96 well plates.…”

Section: Methodsmentioning

confidence: 99%

“…Patients with severe B-cell deficiency such as X-linked agammaglobulinemia (XLA) can be identified with the KREC assay. A triple assay combining TREC and KREC and β-actin (ACTB) as control was developed [12] for neonatal screening. This was employed in a pilot screening of newborn infants for PID, over the course of three years in the County of Stockholm and we have reported the results of the first two years previously [13].…”

Section: Introductionmentioning

confidence: 99%

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Newborn Screening for Primary Immune Deficiencies with a TREC/KREC/ACTB Triplex Assay—A Three-Year Pilot Study in Sweden

Zetterström

Barbaro

Ohlsson

et al. 2017

IJNS

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Background: Screening newborns for severe combined immunodeficiency (SCID) has become essential, since efficient methods to identify infants with these disorders exist and early stem cell transplantation is life-saving. Method: We performed a three-year screening trial in Stockholm comprised of 89,462 newborn infants. The number of T-cell receptor excision circle (TREC)/kappa-deleting recombination excision circle (KREC)/β-actin (ACTB) copies were quantified simultaneously by real time polymerase chain reaction (PCR) in 3.2 mm punches from dried blood samples taken in the regular neonatal screening program. Results: Five patients with immune deficiencies were identified: two with SCID caused by mutations in the Artemis-and adenosine deaminase gene, respectively, one with ataxia telangiectasia and two with reversible agammagloblinemia, which so far, is of unknown cause. This points to an incidence of SCID at the same level as in other studies (around 1:50,000). In 19 recalled infants, low KREC levels and in one case, also low TREC levels, were caused by immunosuppressive treatment of the mother during pregnancy. The levels normalized within a month in all these infants. The total recall rate was 0.10%, and 40% of the recalled infants were born prematurely (<37 weeks gestation). Among 69 patients with inborn errors of metabolism screened retrospectively, only two, who were severely ill with organic acidemias when the sample was taken, and two with mitochondrial disorders, screened positive.

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“…The TREC/KREC assay was performed as described previously, [12,13]. Briefly, DNA was extracted from single 3.2 mm diameter punches of the DBS in 96 well plates.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Newborn Screening for Primary Immune Deficiencies with a TREC/KREC/ACTB Triplex Assay—A Three-Year Pilot Study in Sweden

Zetterström

Barbaro

Ohlsson

et al. 2017

IJNS

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“…As T-B-SCID is the prevalent form of SCID in Israel, whether due to ARTEMIS or RAG mutations, it stands to reason that screening for B cell deficiency (via measurement of the Kappa-deleting receptor excision circle, KREC, alongside TREC) would amplify the sensitivity of SCID screening in Israel, while also allowing for the detection of exclusively B cell deficiencies [30].…”

Section: Screening Reveals Increased Prevalence Of Artemis Mutationsmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency in Israel

Rechavi

Lev

Saraf-Levy

et al. 2017

IJNS

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Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC) quantification in dried blood spots (DBS) has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS) mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.

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“…In a screening setting, the phenotype of P2 with normal TRECs and reduced KRECs would have rather predicted a B-cell and not a T-cell deficiency. 11 In addition, we also performed tandem mass spectrometry for the detection of elevated adenosine metabolites 12 and identified that increased levels of desoxiadenosine and adenosine were already present at birth.…”

Section: To the Editormentioning

confidence: 99%