Abstract
Purpose
To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS).
Methods
The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency.
Results
During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and 87 with a clinically significant non-SCID abnormality based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses included two patients with adenosine deaminase deficiency, three patients with typical and one with leaky IL2RG-related SCID, one patient with IL7Rα-related SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable in eight of the nine babies with typical SCID. Infants with other non-SCID conditions included 27 patients with a syndrome that included T-cell impairment, 18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment secondary to another clinically significant condition, and 13 were classified as ‘other’. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have since resolved, and the remainder continues to be followed. One infant with undetectable TRECs had normal follow-up studies. Molecular studies revealed the presence of two changes in the infant’s DNA.
Conclusions
Overall, ten infants with SCID were identified during the first 2 years of screening in NYS, yielding an incidence of approximately 1 in 48,500 live births, which is consistent with the incidence observed by other states screening for SCID. The incidence of any clinically significant laboratory abnormality was approximately 1 in 5,000; both estimates are higher than estimates prior to the onset of newborn screening for SCID. Improvements to the NYS algorithm included the addition of a borderline category that reduced the proportion of infants referred for flow cytometric analysis, without decreasing sensitivity. We identified a large number of infants with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term follow-up studies are needed to determine the prognosis and optimal treatment for this group of patients, some of whom may present with previously unrecognized, transient lymphopenia of infancy.
Similar content being viewed by others
References
Buckley RH. The long quest for neonatal screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2012;129(3):597–604.
Adeli MM, Buckley RH. Why newborn screening for severe combined immunodeficiency is essential: a case report. Pediatrics. 2010;126(2):e465–9.
Puck JM. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles. J Allergy Clin Immunol. 2012;129(3):607–16.
Chan A, Scalchunes C, Boyle M, Puck JM. Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. Clin Immunol (Orlando, FL). 2011;138(1):3–8.
Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126(3):602–10.e1–11.
Baker MW, Grossman WJ, Laessig RH, Hoffman GL, Brokopp CD, Kurtycz DF, et al. Development of a routine newborn screening protocol for severe combined immunodeficiency. J Allergy Clin Immunol. 2009;124(3):522–7.
Kwan A, Church JA, Cowan MJ, Agarwal R, Kapoor N, Kohn DB, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. J Allergy Clin Immunol. 2013;132(1):140–7.
Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res. 2011;49(1–3):25–43.
Puck JM. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007;120(4):760–8.
Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391–8.
Comeau AM, Hale JE, Pai S-Y, Bonilla FA, Notarangelo LD, Pasternack MS, et al. Guidelines for implementation of population-based newborn screening for severe combined immunodeficiency. J Inherit Metab Dis. 2010;33 Suppl 2:S273–81.
Thompson JG, Wilkey JF, Baptiste JC, Navas JS, Pai S-Y, Pass KA. Development of a high throughput multiplexed TREC qPCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screening. Clin Chem. 2010;56(9):1466–74.
Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, et al. Statewide newborn screening for severe T-cell lymphopenia. J Allergy Clin Immunol. 2009;302(22):2465–70.
Baker MW, Laessig RH, Katcher ML, Routes JM, Grossman WJ, Verbsky J, et al. Implementing routine testing for severe combined immunodeficiency within Wisconsin’s newborn screening program. Public Health Rep (Washington, DC: 1974). 2010;125 Suppl 2:88–95.
Verbsky J, Thakar M, Routes J. The Wisconsin approach to newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2012;129(3):622–7.
Verbsky JW, Baker MW, Grossman WJ, Hintermeyer M, Dasu T, Bonacci B, et al. Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008–2011). J Clin Immunol. 2012;32(1):82–8.
Borte S, Wang N, Oskarsdóttir S, Von Döbeln U, Hammarström L. Newborn screening for primary immunodeficiencies: beyond SCID and XLA. Ann N Y Acad Sci. 2011;1246:118–30.
Saavedra-Matiz CA, Isabelle JT, Biski CK, Duva SJ, Sweeney ML, Parker AL, et al. Cost-effective and scalable DNA extraction method from dried blood spots. Clin Chem. 2013.
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55(4):611–22.
No Title [Internet]. Available from: https://www.nbstrn.org/sites/default/files/SCID%20National%20Monthly%20March%202012.pdf.
Hannon WH, Abraham RS, Kobrynski L, Vogt RF, Adair O, Constantino A, et al. NBS06-A Newborn blood spot screening for severe combined immunodeficiency by measurement of T-cell receptor excision circles; approved guideline. Clinical Standards and Laboratory Institute; 2013;1–92.
Rope AF, Cragun DL, Saal HM, Hopkin RJ. DiGeorge anomaly in the absence of chromosome 22q11.2 deletion. J Pediatr. 2009;155(4):560–5.
1000 Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.
Lim E-M, Cembrowski G, Cembrowski M, Clarke G. Race-specific WBC and neutrophil count reference intervals. Int J Lab Hematol. 2010;32(6 Pt 2):590–7.
Tollerud DJ, Brown LM, Blattner WA, Mann DL, Pankiw-Trost L, Hoover RN. T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier. Am Rev Respir Dis. 1991;144(3 Pt 1):612–6.
Reiner AP, Lettre G, Nalls MA, Ganesh SK, Mathias R, Austin MA, et al. Genome-wide association study of white blood cell count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT). PLoS Genet. 2011;7(6):e1002108.
Ward CE, Baptist AP. Challenges of newborn severe combined immunodeficiency screening among premature infants. Pediatrics. 2013;131(4):e1298–302.
Lima K, Abrahamsen TG, Foelling I, Natvig S, Ryder LP, Olaussen RW. Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+T cell counts and T cell receptor rearrangement excision circles. Clin Exp Immunol. 2010;161(1):98–107.
McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90(1):1–18.
Bales AM, Zaleski CA, McPherson EW. Newborn screening programs: should 22q11 deletion syndrome be added? Genet Med. 2010;12(3):135–44.
Prada N, Nasi M, Troiano L, Roat E, Pinti M, Nemes E, et al. Direct analysis of thymic function in children with Down’s syndrome. Immun Ageing. 2005;2(1):4.
Roat E, Prada N, Lugli E, Nasi M, Ferraresi R, Troiano L, et al. Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome. Rejuvenation Res. 2008;11(3):573–83.
Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Lorey F, Tang LF, et al. Newborn screening for SCID identifies patients with ataxia telangiectasia. J Clin Immunol. 2013;33(3):540–9.
Acknowledgments
Funding was provided by the Eunice Kennedy Shriver Institute for Child Health and Human Development, the Jeffrey Modell Foundation and the New York State Department of Health. Victoria Popson was responsible for most of the follow-up at the Newborn Screening Program.
Author information
Authors and Affiliations
Corresponding author
Appendix
Appendix
Rights and permissions
About this article
Cite this article
Vogel, B.H., Bonagura, V., Weinberg, G.A. et al. Newborn Screening for SCID in New York State: Experience from the First Two Years. J Clin Immunol 34, 289–303 (2014). https://doi.org/10.1007/s10875-014-0006-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-014-0006-7