title: Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation.
abstract: OBJECTIVE
  Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized by hypohidrosis, dental abnormalities, sparse hair, and immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous mutation within NFKBIA, is very rare and its clinical features remain largely unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA mutation who presented with mild EDA and non-infectious systemic inflammation.
  
  
  METHODS
  The clinical presentation of an AD-EDA-ID patient was described and immunological, genetic, and biochemical analyses were performed, with a focus on nuclear factor kappa B (NF-κB) activation.
  
  
  RESULTS
  The patient presented with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a skin biopsy confirmed the presence of sweat glands. There were no dental abnormalities. The patient also suffered from non-infectious inflammation, which responded to systemic corticosteroid therapy; however, the patient remained ill. Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in NFKBIA, resulting in defective NFKBIA degradation and impaired NF-κB activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic stem cell transplantation. Engraftment was successful, with few signs of acute graft versus host disease. However, the patient suffered hemolytic anemia and thrombocytopenia, and died from a brain hemorrhage due to intractable thrombocytopenia.
  
  
  CONCLUSIONS
  AD-EDA-ID patients can present with mild ectodermal dysplasia and non-infectious inflammation, rather than with recurrent infections. Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical challenge.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.forename: Keiko
authors.initials: K
authors.lastname: Okada
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashii
authors.forename: Ikuo
authors.initials: I
authors.lastname: Okafuji
authors.forename: Seishiro
authors.initials: S
authors.lastname: Nodomi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kawai
authors.forename: Kazushi
authors.initials: K
authors.lastname: Izawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
mesh_terms: D002675:Child, Preschool; D025063:Chromosome Disorders; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004476:Ectodermal Dysplasia / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D017809:Fatal Outcome; D005799:Genes, Dominant; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D007249:Inflammation / Q000235:genetics; D007375:Interleukin-1 / Q000276:immunology; D020300:Intracranial Hemorrhages / Q000209:etiology*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D011183:Postoperative Complications; D013921:Thrombocytopenia / Q000209:etiology*; D051194:Toll-Like Receptor 1 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D020672:I-kappa B Proteins; D007375:Interleukin-1; C000606204:NFKBIA protein, human; D051194:Toll-Like Receptor 1; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha