Newborn screening for SCID in New York State: Experience from the first two years

Beth H. Vogel, Vincent Bonagura, Geoffrey A. Weinberg, Mark Ballow, Jason Isabelle, Lisa Diantonio, April Parker, Allison Young, Charlotte Cunningham-Rundles, Chin To Fong, Jocelyn Celestin, Heather Lehman, Arye Rubinstein, Subhadra Siegel, Leonard Weiner, Carlos Saavedra-Matiz, Denise M. Kay, Michele Caggana

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)289-303
Number of pages15
JournalJournal of Clinical Immunology
Volume34
Issue number3
DOIs
StatePublished - Apr 2014

    Fingerprint

Keywords

  • DiGeorge syndrome
  • Severe Combined Immunodeficiency
  • idiopathic T-cell lymphopenia
  • newborn screening

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Vogel, B. H., Bonagura, V., Weinberg, G. A., Ballow, M., Isabelle, J., Diantonio, L., Parker, A., Young, A., Cunningham-Rundles, C., Fong, C. T., Celestin, J., Lehman, H., Rubinstein, A., Siegel, S., Weiner, L., Saavedra-Matiz, C., Kay, D. M., & Caggana, M. (2014). Newborn screening for SCID in New York State: Experience from the first two years. Journal of Clinical Immunology, 34(3), 289-303. https://doi.org/10.1007/s10875-014-0006-7