Background: Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disease associated with mutations in the autoimmune regulator (AIRE) gene and characterized by mucocutaneous candidiasis (CMC), hypoparathyroidism (HP) and primary adrenal insufficiency (AI). Two of these three components are required for diagnosis.
Objective and hypotheses: To describe Russian patients in terms of clinical, genetic, and immunological parameters.
Method: We have recruited patients with at least one of the major clinical components of APS-1 from all over Russia. Eligible patients were phenotyped, AIRE sequenced, and typical autoantibodies assayed.
Results: We recruited 112 patients (63 females, mean age 19.4 (2.744.6) years) from 102 families who fulfilled either the clinical diagnostic criteria or had at least one disease-causing AIRE mutations. 96 had two or three major components and sixteen had one; six -CMC, seven HP, two AI. 106 patients were AIRE sequenced, and twenty different AIRE mutations were found, ten of them novel (A58V; p.Leu 323serfs*51; A390P;821delG;A399P; del>500Stopp*; K221X;C302(C,Y);L13(P,L); C434(*,C). The Arg257Stopp AIRE mutation was present in 74% of the alleles (63 pts were homozygouse, 27 patients heterozygous). Novel A58V AIRE mutation was found in six patients. Neutralizing autoantibodies against INFω were positive in all but one investigated patient.
Conclusions: We have collected the largest cohort of patients with APS-1 published to date. Arg257STOPP AIRE mutation was the most frequent in Russian population. Ten novel AIRE mutations were found. Autoantibodies to INFω are useful for early diagnosis.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology