Published online April 24, 2006
PEDIATRICS (doi:10.1542/peds.2005-2062)

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EXPERIENCE AND REASON

Transient Hemophagocytosis With Deficient Cellular Cytotoxicity, Monoclonal Immunoglobulin M Gammopathy, Increased T-Cell Numbers, and Hypomorphic NEMO Mutation

Jana M. Pachlopnik Schmid, MD, PhD^a, Sonja A. Junge, MD, PhD^a, Johann Peter Hossle, PhD^a, E. Marion Schneider, PhD^b, Eddy Roosnek, PhD^c, Reinhard A. Seger, MD^a, Tayfun Gungor, MD^a

^a Division of Immunology/Hematology/BMT, University Children's Hospital, Zurich, Switzerland
^b Section of Experimental Anesthesiology, University of Ulm, Ulm, Germany
^c Division of Immunology and Allergology, University Hospital, Geneva, Switzerland

X-linked osteopetrosis, anhydrotic ectodermal dysplasia, and immunodeficiency (XL-O-EDA-ID) is a disorder that is caused by hypomorphic mutations in the nuclear factor B essential modulator (NEMO). These mutations lead to an impaired NF-B activation. In vitro analyses and studies in animal models show that inhibition of NF-B leads to a decrease of cytokine production and T-cell proliferation. Patients classically display poor or delayed inflammatory response to infections. We describe a boy with XL-O-EDA-ID, 1167-1168insC NEMO mutation, and recurrent infections. In early infancy, he experienced hemophagocytosis with transient deficiency of natural killer activity. Increased immunoglobulin M levels in blood resulted from a monoclonal immunoglobulin M gammopathy. Blood T-cell numbers were constantly increased, most probably resulting from a peripheral T-cell expansion. Our observations suggest that patients with hypomorphic NEMO mutations and repeated infections may experience inflammatory dysregulation.

Key Words: NEMO • immunodeficiency • hemophagocytic disease • monoclonal gammopathy • T-cell receptor excision circles

Abbreviations: NF-B, nuclear factor B • NEMO, NF-B essential modulator • EDA, anhydrotic ectodermal dysplasia • TNF, tumor necrosis factor • IL, interleukin • IgM, immunoglobulin M • CMV, cytomegalovirus • Ig, immunoglobulin • NK, natural killer • XL-O-EDA-ID, X chromosome–linked anhydrotic ectodermal dysplasia with immunodeficiency and osteopetrosis • TCR, T-cell receptor • TREC, T-cell receptor excision circles • PBMC, peripheral blood mononuclear cell • IVIg, intravenous immunoglobulin • PCR, polymerase chain reaction

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Accepted Nov 14, 2005.

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