title: Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease.
abstract: BACKGROUND
  Autoimmune polyendocrine syndrome type I (APS I) is a monogenic disease affecting endocrine glands and other organs due to mutations of the autoimmune regulator (AIRE) gene. There is a wide variability in clinical phenotypes in patients with APS I, which makes the diagnosis a challenge.
  
  
  OBJECTIVE
  To screen for APS I among Slovakian patients with sporadic Addison's disease and clinical features that raised the suspicion of APS I.
  
  
  METHODS
  All 14 exons and exon-intron boundaries of the AIRE gene were sequenced. In addition, autoantibodies specific for Addison's disease and polyendocrine syndromes were assayed.
  
  
  RESULTS
  Using clinical criteria we identified four patients with APS I in three families. Two patients had a novel missense mutation in exon 2 (c.274C>T, p.R92W) and either the Finnish major mutation (c.769C>T) or the common 13 bp deletion (c.967-979del13bp). APS I was diagnosed in a brother of the latter after his death due to an adrenal crisis. A fourth patient had primary adrenal failure and hypoparathyroidism without AIRE mutations or APS-I specific autoantibodies.
  
  
  CONCLUSIONS
  Four patients with APS I were found in a Slovakian cohort of Addison patients, although the lack of detectable AIRE mutations and APS I-specific autoantibodies raises uncertainty regarding the pathogenesis in one of the patients. This study demonstrates the merits of screening patients with phenotypic features or autoantibody findings that could indicate APS I, even in adult patients. It is necessary to identify APS I patients in order to provide appropriate treatment and follow-up of the various components of APS I.
authors.affiliation: Institute for Clinical Medicine, University of Bergen, N-5021 Bergen, Norway.
authors.forename: Ng'weina
authors.initials: N
authors.lastname: F Magitta
authors.forename: Mikulás
authors.initials: M
authors.lastname: Pura
authors.forename: Anette
authors.initials: A
authors.lastname: S Bøe Wolff
authors.forename: Peter
authors.initials: P
authors.lastname: Vanuga
authors.forename: Anthony
authors.initials: A
authors.lastname: Meager
authors.forename: Per
authors.initials: P
authors.lastname: M Knappskog
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
mesh_terms: D000224:Addison Disease / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D018154:Slovakia; D014157:Transcription Factors / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D014157:Transcription Factors; D000096927:AIRE Protein