Type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED); a 'rare' manifestation in a 'rare' disease

Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease,caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein playsan important role in the establishment of the immunological tolerance acting as a transcriptionalregulator of the expression of organ-specific antigens within the thymus in perinatal age. While a highprevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients arealso detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries.The syndrome is diagnosed when patients present at least two out of the three fundamentaldisorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease.Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has beenrarely reported in different series of patients and occurring more frequently in Finnish APECEDpatients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation ofAPECED in different populations highlighting the peculiar genetic and immunological features ofthe disease when occurring in the context of this syndrome.