title: XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease.
abstract: X-linked inhibitor of apoptosis (XIAP) deficiency, caused by BIRC4 mutations, is described to cause X-linked lymphoproliferative disease (XLP) phenotypes. However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1A mutation), XIAP deficiency was originally observed to be associated with a high incidence of hemophagocytic lymphohistiocytosis (HLH) and a lack of lymphoma, suggesting that classification of XIAP deficiency as a cause of XLP may not be entirely accurate. To further characterize XIAP deficiency, we reviewed our experience with 10 patients from 8 unrelated families with BIRC4 mutations. Nine of 10 patients developed HLH by 8 years of age. Most patients presented in infancy, and recurrent HLH was common. There were no cases of lymphoma. Lymphocyte defects thought to contribute to HLH development in SLAM-Associated Protein deficiency were not observed in XIAP deficiency. We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately classified as X-linked familial hemophagocytic lymphohistiocytosis.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA. Rebecca.Marsh@cchmc.org
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Lisa
authors.initials: L
authors.lastname: Madden
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Kitchen
authors.forename: Rajen
authors.initials: R
authors.lastname: Mody
authors.forename: Brad
authors.initials: B
authors.lastname: McClimon
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005434:Flow Cytometry; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000378:metabolism; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human