title: Newborn screening for SCID in New York State: experience from the first two years.
abstract: OBJECTIVE
  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.
authors.affiliation: Newborn Screening Program, Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY, 12201-0509, USA, bmh06@health.state.ny.us.
authors.forename: Beth H
authors.initials: BH
authors.lastname: Vogel
authors.forename: Vincent
authors.initials: V
authors.lastname: Bonagura
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Weinberg
authors.forename: Mark
authors.initials: M
authors.lastname: Ballow
authors.forename: Jason
authors.initials: J
authors.lastname: Isabelle
authors.forename: Lisa
authors.initials: L
authors.lastname: DiAntonio
authors.forename: April
authors.initials: A
authors.lastname: Parker
authors.forename: Allison
authors.initials: A
authors.lastname: Young
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
authors.forename: Chin-To
authors.initials: CT
authors.lastname: Fong
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Celestin
authors.forename: Heather
authors.initials: H
authors.lastname: Lehman
authors.forename: Arye
authors.initials: A
authors.lastname: Rubinstein
authors.forename: Subhadra
authors.initials: S
authors.lastname: Siegel
authors.forename: Leonard
authors.initials: L
authors.lastname: Weiner
authors.forename: Carlos
authors.initials: C
authors.lastname: Saavedra-Matiz
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
mesh_terms: D000465:Algorithms; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D009518:New York; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy