title: X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis.
abstract: X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.
authors: Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Germany; Center for Pediatrics and Aldolescent Medicine, University Medical Center Freiburg, Germany. Electronic address: carsten.speckmann@uniklinik-freiburg.de.
authors: C
authors: C
authors: Speckmann
authors: K
authors: K
authors: Lehmberg
authors: M H
authors: MH
authors: Albert
authors: R B
authors: RB
authors: Damgaard
authors: M
authors: M
authors: Fritsch
authors: M
authors: M
authors: Gyrd-Hansen
authors: A
authors: A
authors: Rensing-Ehl
authors: T
authors: T
authors: Vraetz
authors: B
authors: B
authors: Grimbacher
authors: U
authors: U
authors: Salzer
authors: I
authors: I
authors: Fuchs
authors: H
authors: H
authors: Ufheil
authors: B H
authors: BH
authors: Belohradsky
authors: A
authors: A
authors: Hassan
authors: C M
authors: CM
authors: Cale
authors: M
authors: M
authors: Elawad
authors: B
authors: B
authors: Strahm
authors: S
authors: S
authors: Schibli
authors: M
authors: M
authors: Lauten
authors: M
authors: M
authors: Kohl
authors: J J
authors: JJ
authors: Meerpohl
authors: B
authors: B
authors: Rodeck
authors: R
authors: R
authors: Kolb
authors: W
authors: W
authors: Eberl
authors: J
authors: J
authors: Soerensen
authors: H
authors: H
authors: von Bernuth
authors: M
authors: M
authors: Lorenz
authors: K
authors: K
authors: Schwarz
authors: U
authors: U
authors: Zur Stadt
authors: S
authors: S
authors: Ehl
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D055611:Natural Killer T-Cells / Q000276:immunology; D010641:Phenotype; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: BIRC4; Hematopoietic stem cell transplantation; Hemophagocytic lymphohistiocytosis; Inflammatory bowel disease; XIAP