Introduction. 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.
Conclusion. 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.
Uvod. Avtoimunski poliglandularni sindrom tipa 1 (APS-1) je redka avtosomno recesivna bolezen, povezana z mutacijami gena AIRE. Tri najpomembnejše komponente APS-1 so kronična mukokutana kandidiaza (CMC), hipoparatiroidizem (HP) in Addisonova bolezen (AD). Raziskali smo klinične, genetske in imunološke značilnosti slovenskih pediatričnih bolnikov z APS-1.
Metode. Pregledali smo obstoječo medicinsko dokumentacijo 15 bolnikov z APS-1, v izbranih primerih smo opravili dodatne klinične in laboratorijske preiskave. Z genetsko analizo smo prepoznali vzročne mutacije gena AIRE, s sistemom luminiscenčne imunoprecipitacije (LIPS) pa smo določili avtoprotitelesa proti interferonom tipa 1.
Rezultati. Bolniki so imeli izraženo eno do osem različnih komponent bolezni. CMC je bila prisotna pri vseh bolnikih, HP pri 12 od 15 (80 %) in AD pri 8 od 15 (53 %). Zastoj rasti je bil prisoten pri 7 (46 %) bolnikih zaradi hiposomatotropizma, rezistence proti rastnemu hormonu, avtoimunskega tiroiditisa, zdravljenja s kortikosteroidi, malabsorbcije ali sekretorne okvare eksokrinega pankreasa. Prepoznanih je bilo 6 različnih mutacij gena AIRE, najpogostejša mutacija p.R257X je bila opredeljena pri 63,3 % mutiranih alelov. Avtoprotitelesa proti interferonom tipa 1 so bila prisotna pri vseh bolnikih.
Zaključki. APS-1 je redka bolezen s širokim naborom kliničnih značilnosti in je lahko smrtna, če ni prepoznana ali je neprimerno zdravljena. Za zgodnje odkrivanje sta ključnega pomena genetska analiza in določanje protiteles proti interferonom tipa 1. Pri bolnikih z APS-1 je zastoj rasti pogosta komponenta bolezni z različnimi vzroki, pogosto povezanimi z manj značilnimi manifestacijami. APS-1 na različne načine vpliva na kvaliteto življenja bolnikov in je veliko psihološko breme, ki lahko vodi v depresijo in samomorilne misli celo pri mladih bolnikih.
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