title: Clinical, Genetic and Immunological Characteristics of Paediatric Autoimmune Polyglandular Syndrome Type 1 Patients in Slovenia.
abstract: BACKGROUND
  Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive disorder, caused by mutations in the AIRE gene. The major components of APS-1 are chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP) and Addison's disease (AD). Clinical, genetic and immunological characteristics of Slovenian paediatric APS-1 patients were investigated.
  
  
  METHODS
  Existing medical records of 15 APS-1 patients were rewieved, when necessary, additional clinical and laboratory investigations were issued. AIRE gene analysis was performed to identify causative mutations, and autoantibodies against type I interferons were measured by luminescence immunoprecipitation system.
  
  
  RESULTS
  Patients had one to eight different manifestations of the disease. CMC was present in all, HP in 12/15 (80 %) and AD in 8/15 (53 %) patients. Growth retardation, due to hyposomatotropism, growth hormone resistance, autoimmune thyroiditis, corticosteroid treatment, malabsorption or secretory failure of exocrine pancreas, was observed in altogether 7 (46 %) patients. Six different AIRE gene mutations were detected and p.R257X mutation was present in 63.3 % of pathological alleles. Antibodies against type I interferons were detected in all patients.
  
  
  CONCLUSIONS
  APS-1 is a rare disorder with a broad spectrum of clinical manifestations, which, if unrecognized or inadequately treated may be fatal. AIRE gene mutational analysis and autoantibodies against type I interferons are important in early identification of the disease. The aetiology of growth retardation was shown to be extremely diverse, frequently caused by less characteristic manifestations. APS-1 may affect patients' quality of life in numerous ways, and may cause great psychosocial burden leading to depression and suicidal thoughts even in paediatric patients.
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanic
authors.affiliation: University of Tartu, Institute of Biomedicine and Translational Medicine, Ravila 19, 50411, Tartu, Estonia.
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Avbelj Stefanija
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.affiliation: University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia; University Medical Centre Ljubljana, University Children's Hospital, Unit for Special Laboratory Diagnostics, Vrazov trg 1, 1000 Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebusak Podkrajsek
keywords: AIRE; APECED; APS-1; autoimmunity