Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1

Abstract

The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.

Autoimmune Polyendocrine Syndromes

“…5–9 Such findings should prompt clinicians to consider the diagnosis of APS-1, especially in young persons. Rarely, retinitis, metaphyseal dysplasia, pure red cell aplasia 8 and polyarthritis 10 have been associated with APS-1 (Fig. 1).…”

“…Several recent case series indicate that the phenotypic variation and age of symptom onset vary greatly, even within the same family, 6–8,11 implying that other genes such as major histocompatibility complex genes, 12 or environmental exposures, influence the phenotype and natural course. For example, a recent Norwegian survey reported that only 40 % of affected patients developed all three main components of APS-1.…”

“…The Finnish major mutation is especially prevalent in people in Finland, Russia, and Eastern Europe. 8,18 Another common mutation is the so-called 13 base pair deletion (p.C322del13) in the histone protein reading region called plant homeodomain 1 (PHD1), prevalent in persons in Norway, the British Isles, France, and North-America. 6,7,19 Additionally, patients with unique dominant negative mutations in AIRE with autosomal dominant inheritance have recently been identified.…”

“…Some minor components of APS-1 develop early in life (keratitis, periodic fever with rash, autoimmune hepatitis), 7 while others occur later (primary ovarian insufficiency under 30 years of age, enamel hypoplasia). 6 Since over 95% of patients with APS-1 have autoantibodies to type 1 interferons, 6,8 broad testing for such antibodies in suspected cases may be useful. In Fig.…”

Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy

“…APECED/APS‐1 is a rare monogenic disorder characterized by development of multiorgan autoimmunity that targets several endocrine and non‐endocrine tissues, and susceptibility to a “signature” infectious disease, chronic mucocutaneous candidiasis (CMC), which manifests with chronic, recurrent and severe infections of the mucous membranes, skin and/or nails by the commensal yeast fungus Candida . Since the initial clinical descriptions of APECED/APS‐1 in the medical literature in between 1929 and 1943 and the subsequent discovery of its genetic etiology via heroic positional cloning efforts by the Finnish‐German Consortium and Dr. Shimizu's research group in 1997, there have been significant advances in our understanding of this rare disease.…”