title: Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR.
abstract: Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections. The lack of functional T or B lymphocytes in these diseases serves as a diagnostic criterion and can be applied to neonatal screening. A robust triplex PCR method for quantitation of T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs), using a single Guthrie card punch, was developed and validated in a cohort of 2560 anonymized newborn screening cards and in 49 original stored Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia, Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A deficiency, or X-linked hyper-IgM syndrome. Simultaneous measurement of TREC and KREC copy numbers in Guthrie card samples readily identified patients with SCID, XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates effective newborn screening for severe immunodeficiency syndromes characterized by the absence of T or B cells.
authors: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. stephan.borte@ki.se
authors: Stephan
authors: S
authors: Borte
authors: Ulrika
authors: U
authors: von Döbeln
authors: Anders
authors: A
authors: Fasth
authors: Ning
authors: N
authors: Wang
authors: Magdalena
authors: M
authors: Janzi
authors: Jacek
authors: J
authors: Winiarski
authors: Ulrich
authors: U
authors: Sack
authors: Qiang
authors: Q
authors: Pan-Hammarström
authors: Michael
authors: M
authors: Borte
authors: Lennart
authors: L
authors: Hammarström
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D060885:Multiplex Polymerase Chain Reaction; D015997:Neonatal Screening; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell