title: Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia.
abstract: BACKGROUND
  Amorphic mutations in the X-linked nuclear factor kappaB essential modulator ( NEMO ) gene cause Incontinentia pigmenti, which is lethal in hemizygous male patients. Hypomorphic NEMO mutations in male patients lead to anhidrotic ectodermal dysplasia (EDA) with immunodeficiency.
  
  
  OBJECTIVE
  To report the clinical features of a child bearing a NEMO mutation who displayed an immunodeficiency without EDA.
  
  
  METHODS
  Documentation of clinical care, chart review, standard immunologic and microbiological laboratory techniques, mutation analysis of the NEMO gene.
  
  
  RESULTS
  Since the age of 15 months, the patient had Mycobacterium avium disease, beginning with multiple adenitis, later followed by disseminated osteomyelitis and dermatitis. In addition, Haemophilus influenzae and Streptococcus pneumoniae infections led to bronchiectasis. An immunologic work-up revealed a low production of IFN-gamma by PBMCs associated with a hyper-IgM phenotype. Despite treatment using repeated cycles of a 4-drug antimycobacterial regimen, continuous subcutaneous IFN-gamma, repeated antibiotic treatment, and intravenous immunoglobulin substitution, the boy remained chronically ill. At the age of 12 years, the disease was complicated by severe autoimmune hemolytic anemia and eventually fatal herpes simplex virus 1 encephalitis despite high-dose acyclovir therapy. Although he did not present any sign of EDA, a novel type of disease-causing hypomorphic NEMO mutation (110-111insC in exon 2) was identified.
  
  
  CONCLUSIONS
  This case demonstrates that patients hemizygous for NEMO mutations can present with an immunodeficiency without EDA. An investigation of NEMO should thus be undertaken in selected children with immunodeficiency despite the lack of EDA.
authors.affiliation: Department of Pediatric Oncology, Heine Universität, Duesseldorf, Germany. niehues@uni-duesseldorf.de
authors.forename: Tim
authors.initials: T
authors.lastname: Niehues
authors.forename: Janine
authors.initials: J
authors.lastname: Reichenbach
authors.forename: Jennifer
authors.initials: J
authors.lastname: Neubert
authors.forename: Sonja
authors.initials: S
authors.lastname: Gudowius
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
authors.forename: Elke
authors.initials: E
authors.lastname: Lainka
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.forename: Horst
authors.initials: H
authors.lastname: Schroten
authors.forename: Rainer
authors.initials: R
authors.lastname: Döffinger
authors.forename: Jean Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Volker
authors.initials: V
authors.lastname: Wahn
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004476:Ectodermal Dysplasia / Q000235:genetics*; D006801:Humans; D051550:I-kappa B Kinase; D007075:Immunoglobulin M / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007371:Interferon-gamma / Q000627:therapeutic use; D008199:Lymphadenitis / Q000209:etiology; D008297:Male; D009154:Mutation
chemical_list: D002352:Carrier Proteins; C491731:IKBKG protein, human; D007075:Immunoglobulin M; D007371:Interferon-gamma; D051550:I-kappa B Kinase