X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis

C. Speckmann; K. Lehmberg; M. H. Albert; R. B. Damgaard; M. Fritsch; M. Gyrd-Hansen; A. Rensing-Ehl; T. Vraetz; B. Grimbacher; U. Salzer; I. Fuchs; H. Ufheil; B. H. Belohradsky; A. Hassan; C. M. Cale; M. Elawad; B. Strahm; S. Schibli; M. Lauten; M. Kohl; J. J. Meerpohl; B. Rodeck; R. Kolb; W. Eberl; J. Soerensen; H. von Bernuth; M. Lorenz; K. Schwarz; U. zur Stadt; S. Ehl

doi:10.1016/j.clim.2013.07.004

X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis

C. Speckmann^*, K. Lehmberg, M. H. Albert, R. B. Damgaard, M. Fritsch, M. Gyrd-Hansen, A. Rensing-Ehl, T. Vraetz, B. Grimbacher, U. Salzer, I. Fuchs, H. Ufheil, B. H. Belohradsky, A. Hassan, C. M. Cale, M. Elawad, B. Strahm, S. Schibli, M. Lauten, M. KohlJ. J. Meerpohl, B. Rodeck, R. Kolb, W. Eberl, J. Soerensen, H. von Bernuth, M. Lorenz, K. Schwarz, U. zur Stadt, S. Ehl

^*Corresponding author for this work

Clinic of Pediatric and Adolescent Medicine

150 Citations (Scopus)

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.

Original language	English
Journal	Clinical Immunology
Volume	149
Issue number	1
Pages (from-to)	133-141
Number of pages	9
ISSN	1521-6616
DOIs	https://doi.org/10.1016/j.clim.2013.07.004
Publication status	Published - 10.2013

Funding

We would like to thank the patients and their families for their participation. We also thank the technicians of the Centre of Chronic Immunodeficiency Advanced Diagnostic Unit for excellent technical assistance. This work was supported by, the German Federal Ministry of Education and Research ( BMBF 01 EO 0803 grant to the Centre of Chronic immunodeficiency and BMBF O1 GM 0896 grant to the PID-NET initiative), a Steno Fellowship from the Danish Council for Independent Research (MG‐H), the Lundbeck Foundation (MG‐H), and the Novo Nordisk Foundation (MG-H).

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.clim.2013.07.004

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Speckmann, C., Lehmberg, K., Albert, M. H., Damgaard, R. B., Fritsch, M., Gyrd-Hansen, M., Rensing-Ehl, A., Vraetz, T., Grimbacher, B., Salzer, U., Fuchs, I., Ufheil, H., Belohradsky, B. H., Hassan, A., Cale, C. M., Elawad, M., Strahm, B., Schibli, S., Lauten, M., ... Ehl, S. (2013). X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis. Clinical Immunology, 149(1), 133-141. https://doi.org/10.1016/j.clim.2013.07.004

@article{8c4f05a7050d4920acb5e4e5b5dcd87d,

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.",

author = "C. Speckmann and K. Lehmberg and Albert, \{M. H.\} and Damgaard, \{R. B.\} and M. Fritsch and M. Gyrd-Hansen and A. Rensing-Ehl and T. Vraetz and B. Grimbacher and U. Salzer and I. Fuchs and H. Ufheil and Belohradsky, \{B. H.\} and A. Hassan and Cale, \{C. M.\} and M. Elawad and B. Strahm and S. Schibli and M. Lauten and M. Kohl and Meerpohl, \{J. J.\} and B. Rodeck and R. Kolb and W. Eberl and J. Soerensen and \{von Bernuth\}, H. and M. Lorenz and K. Schwarz and \{zur Stadt\}, U. and S. Ehl",

note = "Funding Information: We would like to thank the patients and their families for their participation. We also thank the technicians of the Centre of Chronic Immunodeficiency Advanced Diagnostic Unit for excellent technical assistance. This work was supported by, the German Federal Ministry of Education and Research ( BMBF 01 EO 0803 grant to the Centre of Chronic immunodeficiency and BMBF O1 GM 0896 grant to the PID-NET initiative), a Steno Fellowship from the Danish Council for Independent Research (MG‐H), the Lundbeck Foundation (MG‐H), and the Novo Nordisk Foundation (MG-H). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.",

year = "2013",

month = oct,

doi = "10.1016/j.clim.2013.07.004",

language = "English",

volume = "149",

pages = "133--141",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

number = "1",

}

Speckmann, C, Lehmberg, K, Albert, MH, Damgaard, RB, Fritsch, M, Gyrd-Hansen, M, Rensing-Ehl, A, Vraetz, T, Grimbacher, B, Salzer, U, Fuchs, I, Ufheil, H, Belohradsky, BH, Hassan, A, Cale, CM, Elawad, M, Strahm, B, Schibli, S, Lauten, M, Kohl, M, Meerpohl, JJ, Rodeck, B, Kolb, R, Eberl, W, Soerensen, J, von Bernuth, H, Lorenz, M, Schwarz, K, zur Stadt, U & Ehl, S 2013, 'X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis', Clinical Immunology, vol. 149, no. 1, pp. 133-141. https://doi.org/10.1016/j.clim.2013.07.004

TY - JOUR

T1 - X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis

AU - Speckmann, C.

AU - Lehmberg, K.

AU - Albert, M. H.

AU - Damgaard, R. B.

AU - Fritsch, M.

AU - Gyrd-Hansen, M.

AU - Rensing-Ehl, A.

AU - Vraetz, T.

AU - Grimbacher, B.

AU - Salzer, U.

AU - Fuchs, I.

AU - Ufheil, H.

AU - Belohradsky, B. H.

AU - Hassan, A.

AU - Cale, C. M.

AU - Elawad, M.

AU - Strahm, B.

AU - Schibli, S.

AU - Lauten, M.

AU - Kohl, M.

AU - Meerpohl, J. J.

AU - Rodeck, B.

AU - Kolb, R.

AU - Eberl, W.

AU - Soerensen, J.

AU - von Bernuth, H.

AU - Lorenz, M.

AU - Schwarz, K.

AU - zur Stadt, U.

AU - Ehl, S.

N1 - Funding Information: We would like to thank the patients and their families for their participation. We also thank the technicians of the Centre of Chronic Immunodeficiency Advanced Diagnostic Unit for excellent technical assistance. This work was supported by, the German Federal Ministry of Education and Research ( BMBF 01 EO 0803 grant to the Centre of Chronic immunodeficiency and BMBF O1 GM 0896 grant to the PID-NET initiative), a Steno Fellowship from the Danish Council for Independent Research (MG‐H), the Lundbeck Foundation (MG‐H), and the Novo Nordisk Foundation (MG-H). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84883228121

U2 - 10.1016/j.clim.2013.07.004

DO - 10.1016/j.clim.2013.07.004

M3 - Journal articles

C2 - 23973892

AN - SCOPUS:84883228121

SN - 1521-6616

VL - 149

SP - 133

EP - 141

JO - Clinical Immunology

JF - Clinical Immunology

IS - 1

ER -

X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis

Abstract

Funding

Research Areas and Centers

UN SDGs

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