title: Newborn screening for severe T and B cell lymphopenia identifies a fraction of patients with Wiskott-Aldrich syndrome.
abstract: The lack or marked reduction of recently formed T and B cells provides a basis for neonatal screening for severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). Newborns with other conditions are also identified if a severe T or B cell lymphopenia is present at birth. We retrospectively analyzed Guthrie card samples from 11 children with Wiskott-Aldrich syndrome (WAS), a rare disease that requires early diagnosis and treatment, to determine whether combined T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) screening could identify these patients. 4 of 11 patients showed markedly reduced TREC or KREC copy numbers in their DBS as compared to storage-time matched controls and prospectively screened Swedish and German newborns. No correlation was observed between the WAS gene mutations, the clinical severity/course and the result of the screening assay. A diagnosis of WAS should thus be considered in newborns with positive TREC or KREC screening results.
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany; ImmunoDeficiencyCenter Leipzig (IDCL), Hospital St. Georg gGmbH Leipzig, Leipzig, Germany. Electronic address: Stephan.Borte@ki.se.
authors.forename: Stephan
authors.initials: S
authors.lastname: Borte
authors.affiliation: Department of Pediatrics, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.affiliation: Division of Metabolic Diseases (CMMS), Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Stockholm, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: von Döbeln
authors.affiliation: Division of Pediatrics (CLINTEC), Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jacek
authors.initials: J
authors.lastname: Winiarski
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D004247:DNA / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008231:Lymphopenia / Q000175:diagnosis* / Q000473:pathology; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis* / Q000473:pathology
chemical_list: D004247:DNA
keywords: Kappa-deleting recombination excision circles;; Newborn screening;; Severe combined immunodeficiency; T cell receptor excision circles;; Wiskott–Aldrich syndrome;