Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: Results of the first 2 years - 27/06/13
Abstract |
Background |
Assay of T-cell receptor excision circles (TRECs) in dried blood spots obtained at birth permits population-based newborn screening (NBS) for severe combined immunodeficiency (SCID).
Objective |
We sought to report the first 2 years of TREC NBS in California.
Methods |
Since August 2010, California has conducted SCID NBS. A high-throughput TREC quantitative PCR assay with DNA isolated from routine dried blood spots was developed. Samples with initial low TREC numbers had repeat DNA isolation with quantitative PCR for TRECs and a genomic control, and immunophenotyping was performed within the screening program for infants with incomplete or abnormal results. Outcomes were tracked.
Results |
Of 993,724 infants screened, 50 (1/19,900 [0.005%]) had significant T-cell lymphopenia. Fifteen (1/66,250) required hematopoietic cell or thymus transplantation or gene therapy; these infants had typical SCID (n = 11), leaky SCID or Omenn syndrome (n = 3), or complete DiGeorge syndrome (n = 1). Survival to date in this group is 93%. Other T-cell lymphopenic infants had variant SCID or combined immunodeficiency (n = 6), genetic syndromes associated with T-cell impairment (n = 12), secondary T-cell lymphopenia (n = 9), or preterm birth (n = 8). All T-cell lymphopenic infants avoided live vaccines and received appropriate interventions to prevent infections. TREC test specificity was excellent: only 0.08% of infants required a second test, and 0.016% required lymphocyte phenotyping by using flow cytometry.
Conclusions |
TREC NBS in California has achieved early diagnosis of SCID and other conditions with T-cell lymphopenia, facilitating management and optimizing outcomes. Furthermore, NBS has revealed the incidence, causes, and follow-up of T-cell lymphopenia in a large diverse population.
Le texte complet de cet article est disponible en PDF.Key words : Severe combined immunodeficiency, newborn screening, T-cell receptor excision circle, T-cell lymphopenia, DiGeorge syndrome
Abbreviations used : CHARGE, CHH, DBS, HCT, IL-7R, NBS, NICU, NK, qPCR, RAG, SCID, TCL, TREC
Plan
| Support for the initial phase of CA SCID screening was provided by contract HHSN267200603430C to New York State from the Eunice Kennedy Shriver Institute of Child Health and Development, the Jeffrey Modell Foundation, and Perkin Elmer Genetics. Analysis of SCID cases was supported by the Primary Immune Deficiency Treatment Consortium, NIH AI U54 082973, with case development criteria facilitated by NIH R13 AI094943 from the NIH Office of Rare Disease Research of the National Center for Advancing Translational Sciences (NCATS). J.M.P. received NIH support from NCATS 1UL1 RR024131 (UCSF CTSI), RO3 HD 060311 and RO1 AI 078248. A.K. was supported by an HCA International Foundation Travelling Scholarship. |
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| Disclosure of potential conflict of interest: A. Kwan has received a grant for a traveling fellowship from HCA International Foundation. S. A. McGhee has received payment for lectures including service on speakers' bureaus from Baxter. R. Currier is a member of the board for and has received reimbursement for travel to meetings from Newborn Screening Translational Research Network Steering Committee, is employed by the California Department of Public Health, has patents (planned, pending or issued) for multi-analyte interpretation tool in R4S website. E. R. Stiehm has consultant arrangements with UpToDate, has provided expert testimony for the US Department of Justice, and has received payment for lectures including service on speakers' bureaus. M. Porteus has received grants from the National Institutes of Health (NIH). C. P. Aznar has received grants from the Jeffrey Modell Foundation and the NIH, and has received support for travel to meetings for the study or other purposes from the Centers for Disease Control and Prevention/Association of Public Health Laboratories. F. Lorey is employed by the California Department of Public Health. J. M. Puck has received grants from the NIH and the Jeffrey Modell Foundation. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 1
P. 140 - juillet 2013 Retour au numéro
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