{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:46:53Z","timestamp":1791118013379,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T00:00:00Z","timestamp":1464307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01EO1303"],"award-info":[{"award-number":["01EO1303"]}]},{"name":"German Federal Ministry of Education and Research","award":["01GM1111B"],"award-info":[{"award-number":["01GM1111B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autosomal dominant gain\u2010of\u2010function mutations in <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3R1 encoding for the regulatory subunit (p85\u03b1, p55\u03b1, and p50\u03b1) of Class <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content> phosphoinositide 3\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K) result in the activated <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\u03b4 syndrome (<jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>) type 2 characterized by childhood\u2010onset combined immunodeficiency, lymphoproliferation, and immune dysregulation. To improve clinical awareness and understanding of these rare diseases, we reviewed all hitherto published cases with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content> type 1 and type 2 for their clinical and immunologic symptoms and added novel clinical, immunologic, and genetic findings of two patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content> type 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical, immunologic, and genetic evaluation of two new patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>2 was performed followed by the systematic collection of all available previously published data of patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content> type 1 (n\u00a0=\u00a049) and type 2 (n\u00a0=\u00a015) showed an indistinguishable immunologic phenotype. Overlapping clinical features shared by <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content> type 1 and type 2 were observed, but our review also revealed previously unnoticed clinical differences such as remarkably high incidence of microcephaly, poor growth\/short stature in patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>2. Clinical management and outcome were variable and included prophylactic antibiotics, immunosuppression, immunoglobulin substitution, and hematopoietic stem cell transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A disease\u2010specific registry collecting prospective and long\u2010term follow\u2010up data of patients with <jats:styled-content style=\"fixed-case\">APDS<\/jats:styled-content>, as currently set up by the European Society for Immunodeficiencies, are needed to better understand the natural history and to optimize treatment concepts and thereby improving the outcome of this heterogenous patient group.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pai.12585","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T10:46:55Z","timestamp":1461754015000},"page":"640-644","source":"Crossref","is-referenced-by-count":56,"title":["Activated <scp>PI<\/scp>3K\u03b4 syndrome type 2: Two patients, a novel mutation, and review of the literature"],"prefix":"10.1111","volume":"27","author":[{"given":"Peter","family":"Olbrich","sequence":"first","affiliation":[{"name":"Seccion de Infectolog\u00eda e Inmunopatolog\u00eda Unidad de Pediatria Hospital Virgen del Roc\u00edo Sevilla\/Instituto de Biomedicina de Sevilla (IBiS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Lorenz","sequence":"additional","affiliation":[{"name":"The Institute for Transfusion Medicine University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cura Daball","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Medical Center \u2013 University of Freiburg Faculty of Medicine University of Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Lucena","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda Hospital Universitario Virgen del Roc\u00edo Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rensing\u2010Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Medical Center \u2013 University of Freiburg Faculty of Medicine University of Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda Hospital Universitario Virgen del Roc\u00edo Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marita","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"The Institute for Transfusion Medicine University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Camacho\u2010Lovillo","sequence":"additional","affiliation":[{"name":"Seccion de Infectolog\u00eda e Inmunopatolog\u00eda Unidad de Pediatria Hospital Virgen del Roc\u00edo Sevilla\/Instituto de Biomedicina de Sevilla (IBiS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Melon","sequence":"additional","affiliation":[{"name":"Seccion de Infectolog\u00eda e Inmunopatolog\u00eda Unidad de Pediatria Hospital Virgen del Roc\u00edo Sevilla\/Instituto de Biomedicina de Sevilla (IBiS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schwarz","sequence":"additional","affiliation":[{"name":"The Institute for Transfusion Medicine University of Ulm Ulm Germany"},{"name":"Institute for Clinical Transfusion Medicine and Immunogenetics Ulm German Red Cross Blood Service Baden\u2010W\u00fcrttemberg\u2010Hessen Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Neth","sequence":"additional","affiliation":[{"name":"Seccion de Infectolog\u00eda e Inmunopatolog\u00eda Unidad de Pediatria Hospital Virgen del Roc\u00edo Sevilla\/Instituto de Biomedicina de Sevilla (IBiS) Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Speckmann","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Medical Center \u2013 University of Freiburg Faculty of Medicine University of Freiburg Germany"},{"name":"Center for Pediatrics Department of Pediatric Hematology and Oncology Medical Center \u2013 University of Freiburg Faculty of Medicine University of Freiburg 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