{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T07:43:49Z","timestamp":1778226229937,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypomorphic mutations in the gene encoding Bruton tyrosine kinase (<jats:italic>BTK<\/jats:italic>) may result in milder phenotypes and delayed diagnosis of B\u2010cell related immunodeficiencies due to residual BTK function. Newborn screening for kappa\u2010deleting\u2010recombination\u2010excision circles (KRECs) reliably identifies classical X\u2010linked agammaglobulinaemia (XLA) patients with profound B\u2010cell lymphopenia at birth but has not been evaluated in patients with residual BTK function. We aimed to evaluate clinical findings, BTK function and KREC copy numbers in three patients with <jats:italic>BTK<\/jats:italic> mutations presenting with impaired polysaccharide responsiveness without agammaglobulinaemia. One patient had an invasive pneumococcal infection at the age of 4\u00a0years. All three patients (two brothers) had visible tonsils, normal to slightly decreased immunoglobulin G levels, undetectable pneumococcal antibodies despite pneumococcal conjugate vaccinations, no antibody response after a diagnostic polysaccharide vaccination as well as profound B\u2010cell lymphopenia with residual B\u2010cell differentiation. <jats:italic>BTK<\/jats:italic> mutations were identified by Sanger sequencing. BTK staining and phosphorylation assays were performed on peripheral B cells. KREC copy numbers were determined from dried blood spots obtained within the first week of life as well as once at the age of 8, 6 and 3\u00a0years, respectively. BTK staining showed residual protein expression. Also, residual BTK activity could be demonstrated. KREC copy numbers from dried blood spots were above the threshold set for detection of patients with profound B\u2010cell lymphopenia. Male patients with impaired polysaccharide responsiveness should be evaluated for B\u2010cell lymphopenia followed by <jats:italic>BTK<\/jats:italic> analyses irrespective of immunoglobulin levels or tonsil size.<\/jats:p>","DOI":"10.1111\/sji.12811","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T06:23:55Z","timestamp":1564986235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired polysaccharide responsiveness without agammaglobulinaemia in three patients with hypomorphic mutations in <i>Bruton Tyrosine Kinase<\/i>\u2014No detection by newborn screening for primary immunodeficiencies"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-9385","authenticated-orcid":false,"given":"Renate","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"Department of Pediatric Pneumology, Immunology and Intensive Care, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin Humboldt\u2010Universit\u00e4t zu Berlin and Berlin Institute of Health Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Borte","sequence":"additional","affiliation":[{"name":"ImmunoDeficiencyCenter Leipzig (IDCL), Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies Municipal Hospital St. Georg Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"K\u00f6lsch","sequence":"additional","affiliation":[{"name":"Department of Immunology Labor Berlin - Charit\u00e9 Vivantes GmbH Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam Ricarda","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, German Red Cross Blood Service Baden\u2010Wuerttemberg\u2013Hessen University Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"},{"name":"Center for Chronic Immunodeficiency, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"},{"name":"Center for Chronic Immunodeficiency, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"},{"name":"Center for Chronic Immunodeficiency, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, Faculty of Medicine, Medical Center\u2010University of Freiburg University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, German Red Cross Blood Service Baden\u2010Wuerttemberg\u2013Hessen University Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Wahn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pneumology, Immunology and Intensive Care, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin Humboldt\u2010Universit\u00e4t zu Berlin and Berlin Institute of Health Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"von Bernuth","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pneumology, Immunology and Intensive Care, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin Humboldt\u2010Universit\u00e4t zu Berlin and Berlin Institute of Health Berlin Germany"},{"name":"Department of Immunology Labor Berlin - Charit\u00e9 Vivantes GmbH Berlin Germany"},{"name":"Berlin Center for Regenerative Therapies (BCRT) Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin 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