1. 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.
- Author
-
Yoshioka, Takakazu, Nishikomori, Ryuta, Hara, Junichi, Okada, Keiko, Hashii, Yoshiko, Okafuji, Ikuo, Nodomi, Seishiro, Kawai, Tomoki, Izawa, Kazushi, Ohnishi, Hidenori, Yasumi, Takahiro, Nakahata, Tatsutoshi, and Heike, Toshio
- Subjects
- *
RAPP-Hodgkin syndrome , *TUMOR necrosis factors , *POLYCYSTIC kidney disease , *IMMUNODEFICIENCY , *GENETIC mutation , *BIOCHEMISTRY , *ADRENOCORTICAL hormones - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF