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

TY - JOUR

T1 - X-linked inhibitor of apoptosis (XIAP) deficiency

T2 - 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, Kai-Uwe

AU - zur Stadt, U.

AU - Ehl, S.

PY - 2013/10/1

Y1 - 2013/10/1

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 - http://www.scopus.com/inward/record.url?scp=84883228121&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2013.07.004

DO - 10.1016/j.clim.2013.07.004

M3 - Journal article

C2 - 23973892

AN - SCOPUS:84883228121

SN - 1521-6616

VL - 149

SP - 133

EP - 141

JO - Clinical Immunology

JF - Clinical Immunology

IS - 1

ER -