title: X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.
abstract: A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.
authors.affiliation: Dr von Haunersches Kinderspital, Ludwig-Maximilians-Universität, Munich, Germany. michael.albert@med.lmu.de
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Tanja C
authors.initials: TC
authors.lastname: Bittner
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Lucia Dora
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Siobhan
authors.initials: S
authors.lastname: Burns
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.forename: Teresa
authors.initials: T
authors.lastname: Espanol
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellier
authors.forename: Gabriele
authors.initials: G
authors.lastname: Strauss
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gathmann
authors.forename: Jeroen G
authors.initials: JG
authors.lastname: Noordzij
authors.forename: Cristina
authors.initials: C
authors.lastname: Fillat
authors.forename: Manfred
authors.initials: M
authors.lastname: Hoenig
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Philipp
authors.initials: P
authors.lastname: Pagel
authors.forename: Uwe
authors.initials: U
authors.lastname: Wintergerst
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D050172:Genes, X-Linked; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D010641:Phenotype; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000150:complications* / Q000235:genetics / Q000401:mortality*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein