Journal Article

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

Yasumi, Takahiro, Heike, Toshio, Nakahata, Tatsutoshi, Okafuji, Ikuo, Izawa, Kazushi, Yoshioka, Takakazu, Nishikomori, Ryuta, Kawai, Tomoki, Hara, Junichi, Hashii, Yoshiko, Ohnishi, Hidenori, Nodomi, Seishiro, Okada, Keiko

2013

Overview

Purpose 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. Conclusion 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.

• Publisher: Springer US,Springer Nature B.V
• Subject: adrenal cortex hormones / Anhidrotic ectodermal dysplasia / Biomedical and Life Sciences / Biomedicine / biopsy / brain / cell transplantation / Child, Preschool / Chromosome Disorders / Disease Progression / DNA Mutational Analysis / ectoderm / Ectodermal Dysplasia - diagnosis / Ectodermal Dysplasia - genetics / Ectodermal Dysplasia - therapy / Fatal Outcome / Genes, Dominant / genetic analysis / Hematopoietic Stem Cell Transplantation / hematopoietic stem cells / hemolytic anemia / hemorrhage / heterozygosity / Humans / I-kappa B Proteins - genetics / I-kappa B Proteins - metabolism / Immunologic Deficiency Syndromes - diagnosis / Immunologic Deficiency Syndromes - genetics / Immunologic Deficiency Syndromes - therapy / Immunology / immunosuppression / Infectious Diseases / inflammation / Inflammation - genetics / Interleukin-1 - immunology / Internal Medicine / Intracranial Hemorrhages - etiology / Male / Medical Microbiology / missense mutation / Mutation, Missense - genetics / NF-KappaB Inhibitor alpha / Original Research / patients / Postoperative Complications / sweat / thrombocytopenia / Thrombocytopenia - etiology / Toll-Like Receptor 1 - immunology / transcription factor NF-kappa B / Tumor Necrosis Factor-alpha - immunology / tumor necrosis factors