title: Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases.
abstract: In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID) is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC) assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ) deficiency). As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency (CID), 1 Wiskott-Aldrich syndrome, and 1 X-linked lymphoproliferative disease). Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982) were tested.Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls.Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.
authors.affiliation: CancerCare Manitoba, 675 McDermot Ave, Winnipeg, Manitoba R3E 0V9, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Jilkina
authors.affiliation: Cadham Provincial Laboratory, 750 William Ave, Winnipeg, Manitoba R3E 3J7, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Thompson
authors.affiliation: CancerCare Manitoba, 675 McDermot Ave, Winnipeg, Manitoba R3E 0V9, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Kwan
authors.affiliation: Cadham Provincial Laboratory, 750 William Ave, Winnipeg, Manitoba R3E 3J7, Canada; Department of Pediatrics and Child Health, University of Manitoba, CE208, 840 Sherbrook Street, Winnipeg, Manitoba R3A 1S1, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Van Caeseele
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, CE208, 840 Sherbrook Street, Winnipeg, Manitoba R3A 1S1, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Rockman-Greenberg
authors.affiliation: CancerCare Manitoba, 675 McDermot Ave, Winnipeg, Manitoba R3E 0V9, Canada; Department of Pediatrics and Child Health, University of Manitoba, CE208, 840 Sherbrook Street, Winnipeg, Manitoba R3A 1S1, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: Schroeder
keywords: ADA, adenosine deaminase deficiency; Archived Guthrie cards; CHH, cartilage–hair hypoplasia; CID, common immune deficiency; CPL, Cadham Provincial Laboratory; DBS, dried blood spots; Dried blood spots; FNMI, First Nations, Metis, and Inuit; HSCT, hematopoietic stem cell transplant; IKKβ, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta; NENSP, New England Newborn Screening Program, NICU, neonatal intensive care unit; Newborn screening; PID, Primary Immunodeficiency Disease; SCID, Severe Combined Immunodeficiency; Severe Combined Immunodeficiency; T-cell positive primary immunodeficiency; T-cell receptor excision circle; TREC, T-cell receptor excision circle; WAS, Wiskott–Aldrich syndrome; XLP, X-linked lymphoproliferative disease; ZAP70, zeta chain-associated protein kinase