title: Gastrointestinal Manifestations in X-linked Agammaglobulinemia.
abstract: OBJECTIVE
  X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in X-linked agammaglobulinemia (XLA), the spectrum of gastrointestinal manifestations has not previously been fully explored.
  
  
  METHODS
  We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the United States Immunodeficiency Network, a national registry of primary immunodeficiencies.
  
  
  RESULTS
  In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide ranging, and management strategies were diverse and mainly experimental.
  
  
  CONCLUSIONS
  Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. sbarmettler@mgh.harvard.edu.
authors.forename: Sara
authors.identifier: http://orcid.org/0000-0001-8188-9187
authors.initials: S
authors.lastname: Barmettler
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.|University of San Francisco, San Francisco, CA, USA.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Otani
authors.affiliation: Lahey Hospital & Medical Center, Burlington, MA, USA.
authors.forename: Jasmit
authors.initials: J
authors.lastname: Minhas
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Roshini S
authors.initials: RS
authors.lastname: Abraham
authors.affiliation: University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
authors.forename: Yenhui
authors.initials: Y
authors.lastname: Chang
authors.affiliation: University of San Francisco, San Francisco, CA, USA.
authors.forename: Morna J
authors.initials: MJ
authors.lastname: Dorsey
authors.affiliation: University of Iowa Hospitals and Clinic, Iowa City, IA, USA.
authors.forename: Zuhair K
authors.initials: ZK
authors.lastname: Ballas
authors.affiliation: Boston Children's Hospital, Boston, MA, USA.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Bonilla
authors.affiliation: Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.|University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
authors.forename: Jolan E
authors.initials: JE
authors.lastname: Walter
mesh_terms: D000361:Agammaglobulinemia / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D000369:Aged, 80 and over; D015415:Biomarkers; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology; D041981:Gastrointestinal Tract / Q000473:pathology*; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D016130:Immunophenotyping; D007223:Infant; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D015415:Biomarkers; D007132:Immunoglobulin Isotypes
keywords: BTK; Bruton’s agammaglobulinemia; GI manifestations; IBD; X-linked agammaglobulinemia; XLA; enteritis; gastrointestinal manifestations; inflammatory bowel disease