J Clin Immunol DOI 10.1007/s10875-014-0006-7
ORIGINAL RESEARCH
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
Received: 29 August 2013 / Accepted: 17 February 2014 # Springer Science+Business Media New York 2014
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
M. Ballow : H. Lehman Women and Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA
G. A. Weinberg : C.T
T-B+NK+ Typical SCID CD3 (33), CD4 (22), CD8 (16), CD19 (866), CD16CD56 (409)
Transplant at age 5 months, unrelated cord blood donor with (6 out 8 match) conditioning, patient currently doing well
2
Male
Undetectable
T-B+NK+ CD3 (334), CD4 (108), CD8 (248), CD19 (378), CD16CD56 (882), CD45RA (
ORIGINAL RESEARCH
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
Received: 29 August 2013 / Accepted: 17 February 2014 # Springer Science+Business Media New York 2014
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
M. Ballow : H. Lehman Women and Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA
G. A. Weinberg : C.T
T-B+NK+ Typical SCID CD3 (33), CD4 (22), CD8 (16), CD19 (866), CD16CD56 (409)
Transplant at age 5 months, unrelated cord blood donor with (6 out 8 match) conditioning, patient currently doing well
2
Male
Undetectable
T-B+NK+ CD3 (334), CD4 (108), CD8 (248), CD19 (378), CD16CD56 (882), CD45RA (
