title: Disseminated BCG infection mimicking metastatic nasopharyngeal carcinoma in an immunodeficient child with a novel hypomorphic NEMO mutation.
abstract: BACKGROUND
  Nuclear factor-κB essential modulator (NEMO) deficiency is a developmental and immunological disorder. The genetic and phenotypic correlation has been described.
  
  
  METHODS
  We report a unique clinical presentation and the identification of a novel missense mutation in the NEMO gene in a 3-year-old boy with bacillus Calmette-Guerin (BCG) infection.
  
  
  RESULTS
  The patient presented with fever, cervical lymphadenopathy, and abnormal anti-Epstein-Barr virus (EBV) antibody titers, suggestive of EBV-related diseases including chronic active EBV infection, X-linked lymphoproliferative syndrome, or nasopharyngeal carcinoma. Although the biopsy specimen from a nasopharyngeal lesion was initially diagnosed as squamous cell carcinoma, this was changed to disseminated BCG infection involving the nasopharynx, multiple systemic lymph nodes, and brain. A novel mutation (designated D311E) in the NEMO gene, located in the NEMO ubiquitin-binding (NUB) domain, was identified as the underlying cause of the immunodeficiency. Impaired immune responses which are characteristic of patients with NEMO deficiency were demonstrated. The patient underwent successful unrelated bone marrow transplantation at 4.9 years of age.
  
  
  CONCLUSIONS
  This study suggests the importance of the NUB domain in host defense against mycobacteria. The unique presenting features in our patient indicate that a hypomorphic NEMO mutation can be associated with atypical pathological findings of the epithelial tissues in patients with BCG infection.
authors.affiliation: Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Imamura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kawai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Kazushi
authors.initials: K
authors.lastname: Izawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takachi
authors.forename: Haruko
authors.initials: H
authors.lastname: Iwabuchi
authors.forename: Sakiko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hosokai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Umezu
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004476:Ectodermal Dysplasia; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D008206:Lymphatic Diseases; D008297:Male; D009154:Mutation / Q000235:genetics; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D014376:Tuberculosis / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D054875:Ubiquitination / Q000235:genetics; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: C491731:IKBKG protein, human; D051550:I-kappa B Kinase