A longitudinal follow-up of autoimmune polyendocrine syndrome type 1
AuthorBruserud, Øyvind; Oftedal, Bergithe Eikeland; Landegren, Nils; Erichsen, Martina Moter; Bratland, Eirik; Lima, Kari; Jørgensen, Anders Palmstrøm; Myhre, Anne Grethe; Svartberg, Johan; Fougner, Kristian J; Bakke, Åsne; Nedrebø, Bjørn Gunnar; Mella, Bjarne; Breivik, Lars Ertesvåg; Viken, Marte K; Knappskog, Per; Cuida Marthinussen, Ileana Mihaela; Løvås, Kristian; Kämpe, Olle; Wolff, Anette Susanne Bøe; Husebye, Eystein Sverre
Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insuffi- ciency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator ( AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent compo- nents.Withage,mostpatientspresentedthreetofivediseasemanifestations,althoughsomehadmilderphenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceasedsiblingswithahighprobabilityofundisclosedAPS1.Allexceptthreehadinterferon- )autoantibodies,and allhadorgan-specificautoantibodies.Themostcommon AIRE mutationwasc.967_979del13,foundinhomozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879 1G A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon- ) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.