Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

“…Testicular insufficiency is less frequent and affects approximately 10 % of male patients; this deficiency usually develops during adulthood [11]. T1D also usually develops during adulthood, with prevalence ranges from a couple of percentages in some populations to approximately 30 % in Finnish patients [7,19,23,[84][85][86][87]. As with isolated T1D, the disease is correlated with autoantibodies against insulin and IA-2 tyrosine phosphatase-like protein; however, autoantibodies to glutamic acid decarboxylase GAD65, a sensitive marker for isolated T1D, are frequently found in APECED patients without T1D [94].…”

“…HP is the most common autoimmune component, with a prevalence that ranges from 77 to 96 % [7,19,23,[84][85][86]. A lower prevalence of 63 % was found among 19 French patients [87].…”

“…The prevalence of AD is reportedly between 63 and 92 %, making it the second most common endocrine disorder [7,19,23,[84][85][86][87]. AD is thought to be mediated by autoreactive cytotoxic T-cells [89][90][91], but the adrenal hormone deficiencies do not manifest clinically until at least 90 % of the functional adrenocortical cells have been destroyed [92,93].…”

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura

“…This clinical heterogeneity in NEMO deficiency is similar at observed in autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) which is caused by mutations in the AIRE gene. This disorder is characterized by a highly variable combination of symptoms such as chronic mucocutaneous candidiasis, polyendocrinopathy, hepatitis, dystrophy of the dental enamel and nails, and production of autoantibodies against different self-antigens (IL-17F, IFN-γ, tryptophan hydroxylase-1 and autoimmune enteropathy-related 75 kDa antigen) [14,15]. The analysis of patients with NEMO deficiency highlight the importance of reaching a consensus whether this syndrome is more complex and includes the susceptibility to microbes accompanied by ectodermal dysplasia or incontinentia pigmenti, as well as immune dysregulation and aberrant control of inflammation [16].…”

Autoimmune Disorders Associated to Type 1 Diabetes Mellitus in Children and Adolescents

“…Type I APS, called also APECED (Autoimmune PolyEndocrinopathy-CandidiasisEctodermal Dystrophy) is a rare autosomal recessive disorder originally identified through the typical association of mucocutaneous candidiasis with Addison's disease and hypoparathyroidism. These symptoms usually constitute the first manifestation of the www.intechopen.com disease in early childhood; other endocrine and non-endocrine disorders can be associated: thyroiditis, autoimmune hypogonadism, hypophysitis, chronic active hepatitis, atrophic gastritis, pernicious anemia, alopecia, vitiligo and ectodermal dystrophy (Mazza et al, 2011). The disease results from the inheritance of recessive genes (AIRE gene) mapping to 21q22.3 and it is not linked to genes within the HLA-DR/DQ genetic region of chromosome 6.…”