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Newborn Screening for SCID in New York State: Experience from the First Two Years

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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.

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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

  1. Women and Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY, 14222, USA

    Mark Ballow & Heather Lehman

  2. Steven and Alexandra Cohen Children’s Medical Center of NY, 865 Northern Boulevard, Room 101, Great Neck, NY, 11021, USA

    Vincent Bonagura

  3. Newborn Screening Program, Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY, 12201-0509, USA

    Beth H. Vogel, Jason Isabelle, Lisa DiAntonio, April Parker, Allison Young, Carlos Saavedra-Matiz, Denise M. Kay & Michele Caggana

  4. Asthma and Allergy Center of Albany Medical Center, 176 Washington Ave Extension, Suite 102, Albany, NY, 12203, USA

    Jocelyn Celestin

  5. Mount Sinai Medical Center, 1425 Madison Avenue, Room 1120, New York, NY, 10029, USA

    Charlotte Cunningham-Rundles

  6. University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 690, Rochester, NY, 14642, USA

    Geoffrey A. Weinberg & Chin-To Fong

  7. Division of Allergy and Immunology, Montefiore Medical Park, 1525 Blondell Avenue, Room 100, Bronx, NY, 10461, USA

    Arye Rubinstein

  8. New York Medical College, Westchester Medical Center, Munger Pavilion Room 106, Valhalla, NY, USA

    Subhadra Siegel

  9. Department of Pediatrics, State University of New York Upstate Medical University, 750 East Adams Street, Room 5400, Syracuse, NY, 13210, USA

    Leonard Weiner

Authors
  1. Beth H. Vogel
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  2. Vincent Bonagura
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  3. Geoffrey A. Weinberg
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  4. Mark Ballow
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  5. Jason Isabelle
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  6. Lisa DiAntonio
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  7. April Parker
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  8. Allison Young
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  9. Charlotte Cunningham-Rundles
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  10. Chin-To Fong
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  11. Jocelyn Celestin
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  12. Heather Lehman
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  13. Arye Rubinstein
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  14. Subhadra Siegel
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  15. Leonard Weiner
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  16. Carlos Saavedra-Matiz
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  17. Denise M. Kay
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  18. Michele Caggana
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Corresponding author

Correspondence to Beth H. Vogel.

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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

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  • DOI: https://doi.org/10.1007/s10875-014-0006-7

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