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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3529-3537. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-05-021402. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2006-05-021402v1 109/8/3529    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuijpers, T. W. Articles by Roos, D. Search for Related Content PubMed PubMed Citation Articles by Kuijpers, T. W. Articles by Roos, D. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 18, 2006 Accepted July 12, 2006 Natural history and early diagnosis of LAD-1/variant syndrome Taco W. Kuijpers*, Robin van Bruggen, Nanne Kamerbeek, Anton T. J. Tool, Gonul Hicsonmez, Aytemiz Gurgey, Axel Karow, Arthur J. Verhoeven, Karl Seeger, Ozden Sanal, Charlotte Niemeyer, and Dirk Roos Emma Children's Hospital, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, AMC, University of Amsterdam, Amsterdam, Netherlands Pediatric Hematology Unit, Hacettepe University, Ankara, Turkey Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany Department of Pediatric Oncology/Hematology, Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charite-Universitatsmedizin, Berlin, Germany Pediatric Immunology Unit, Hacettepe University, Ankara, Turkey * Corresponding author; email: t.w.kuijpers{at}amc.uva.nl. The syndrome of Leukocyte Adhesion Deficiency (LAD)combined with a severe Glanzmann-type bleeding disorder has been recognized as a separate disease entity. The variability in clinical and cell biological terms has remained largely unclear. We present data on 9 cases from 7 unrelated families, with three patients being actively followed for more than 12 years. The disease entity, designated LAD-1/variant syndrome, presents early in life and consists of non-pussing infections from bacterial and fungal origin, as well as a severe bleeding tendency. This is compatible with two major blood cell types contributing to the clinical symptoms, i.e. granulocytes and platelets. In granulocytes of the patients, we found adhesion and chemotaxis defects, as well as a defect in NADPH oxidase activity triggered by unopsonized zymosan. This last test can be used as a screening test for the syndrome. Many proteins and genes involved in adhesion and signaling, including small GTPases such as Rap1 and -2 as well as the major Rap activity-regulating molecules, were normally present. Moreover, Rap1 activation was intact in patients' blood cells. Defining the primary defect awaits genetic linkage analysis, which may be greatly helped by a more precise understanding and awareness of the disease combined with the early identification of affected patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: LAD III versus LAD I variant Amos Etzioni and Ronen Alon Blood 2007 110: 4129. [Full Text] [PDF] Response: Adherence to the LAD variant form Taco Kuijpers, Frank Baas, Marian Weterman, Anton Tool, and Dirk Roos Blood 2007 110: 4129-4130. [Full Text] [PDF] Blood orchestrates a leukocyte integrin trio Joel S. Bennett Blood 2007 109: 3137-3138. [Full Text] [PDF]

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