scholarly journals Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy in Two Siblings: Same Mutations but Very Different Phenotypes

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 169
Author(s):  
Andrea Carpino ◽  
Raffaele Buganza ◽  
Patrizia Matarazzo ◽  
Gerdi Tuli ◽  
Michele Pinon ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Phenotypic Expression ◽  
Monogenic Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Adrenocortical Insufficiency ◽  
Phenotype Correlation ◽  
Exact Role ◽  
Mucocutaneous Candidiasis ◽  
Aire Gene ◽  
Autoimmune Polyendocrinopathy

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), caused by mutations in the AIRE gene, is mainly characterized by the triad of hypoparathyroidism, primary adrenocortical insufficiency and chronic mucocutaneous candidiasis, but can include many other manifestations, with no currently clear genotype–phenotype correlation. We present the clinical features of two siblings, a male and a female, with the same mutations in the AIRE gene associated with two very different phenotypes. Interestingly, the brother recently experienced COVID-19 infection with pneumonia, complicated by hypertension, hypokalemia and hypercalcemia. Although APECED is a monogenic disease, its expressiveness can be extremely different. In addition to the genetic basis, epigenetic and environmental factors might influence the phenotypic expression, although their exact role remains to be elucidated.

scholarly journals Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy: Insights into Genotype-Phenotype Correlation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Donatella Capalbo ◽  
Lucia De Martino ◽  
Giuliana Giardino ◽  
Raffaella Di Mase ◽  
Iolanda Di Donato ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Single Gene ◽  
Monogenic Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Autoimmune Polyendocrinopathy ◽  
Symptoms And Signs ◽  
Chronic Hypoparathyroidism ◽  
Rare Autosomal Recessive Disease

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disease, caused by mutations of a single gene named autoimmune regulator gene (AIRE) which results in a failure of T cell tolerance within the thymus. Chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison’s disease are the hallmarks of the syndrome. APECED is also characterized by several autoimmune endocrine and nonendocrine manifestations, and the phenotype is often complex. Moreover, even though APECED is a monogenic disease, its clinical picture is generally dominated by a wide heterogeneity both in the severity and in the number of components even among siblings with the sameAIREgenotype. The variability of its clinical expression implies that diagnosis can be challenging, and a considerable delay often occurs between the appearance of symptoms and the diagnosis. Since a prompt diagnosis is essential to prevent severe complications, clinicians should be aware of all symptoms and signs of suspicion. The aim of this paper is to give an overview on the clinical presentation and diagnostic criteria of APECED and to focus on current knowledge on genotype-phenotype correlation.

scholarly journals Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines

2010 ◽  
Vol 207 (2) ◽  
pp. 299-308 ◽  
Author(s):  
Kai Kisand ◽  
Anette S. Bøe Wolff ◽  
Katarina Trebušak Podkrajšek ◽  
Liina Tserel ◽  
Maire Link ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Tolerance Induction ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrine Syndrome ◽  
Self Tolerance ◽  
Multicenter Survey ◽  
Autoimmune Polyendocrinopathy ◽  
Patient Groups ◽  
Endocrine Features

Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.

scholarly journals Intracranial Calcifications in Autoimmune Polyendocrine Ectodermal Dystrophy Syndrome (APECED): About A Case Report

2021 ◽  
pp. 1-3
Author(s):  
Benfaddoul O ◽  
◽  
Zouita B ◽  
El azzouzi B ◽  
Basraoui N ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrinopathy ◽  
Life Threatening ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyendocrinopathy ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I (APS I), is an uncommon, but debilitating autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE), It is characterized by a broad and diverse clinical spectrum which can lead to severe metabolic alterations and eventually life-threatening events. Hypoparathyroidism is one of the major criteria for clinical diagnosis, in addition to chronic mucocutaneous candidiasis and autoimmune adrenal insufficiency. This component is responsible for the forming of brain calcifications which tend to have a characteristic predilection for the basal ganglia. In this article, we report an additional case to the literature and provide a literature review of the expanding radiological spectrum of this syndrome

scholarly journals Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

2021 ◽  
Vol 9 ◽  
Author(s):  
Elise M. N. Ferré ◽  
Monica M. Schmitt ◽  
Michail S. Lionakis
Keyword(s):  
Clinical Manifestations ◽  
Chronic Mucocutaneous Candidiasis ◽  
Loss Of Function ◽  
Primary Adrenal Insufficiency ◽  
Autoimmune Polyglandular Syndrome ◽  
Mucocutaneous Candidiasis ◽  
Targeted Screening ◽  
Autoimmune Polyendocrinopathy ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1), is a rare monogenic autoimmune disease caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene. AIRE deficiency impairs immune tolerance in the thymus and results in the peripheral escape of self-reactive T lymphocytes and the generation of several cytokine- and tissue antigen-targeted autoantibodies. APECED features a classic triad of characteristic clinical manifestations consisting of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenal insufficiency (Addison's disease). In addition, APECED patients develop several non-endocrine autoimmune manifestations with variable frequencies, whose recognition by pediatricians should facilitate an earlier diagnosis and allow for the prompt implementation of targeted screening, preventive, and therapeutic strategies. This review summarizes our current understanding of the genetic, immunological, clinical, diagnostic, and treatment features of APECED.

scholarly journals An AIREless Breath: Pneumonitis Caused by Impaired Central Immune Tolerance

2021 ◽  
Vol 11 ◽  
Author(s):  
Elise M. N. Ferré ◽  
Michail S. Lionakis
Keyword(s):  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Chronic Mucocutaneous Candidiasis ◽  
Monogenic Disorder ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Attack ◽  
Autoimmune Polyendocrinopathy ◽  
Life Threatening ◽  
Rag Deficiency ◽  
Biallelic Mutations

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by biallelic mutations in the AIRE gene, has historically been defined by the development of chronic mucocutaneous candidiasis together with autoimmune endocrinopathies, primarily hypoparathyroidism and adrenal insufficiency. Recent work has drawn attention to the development of life-threatening non-endocrine manifestations such as autoimmune pneumonitis, which has previously been poorly recognized and under-reported. In this review, we present the clinical, radiographic, autoantibody, and pulmonary function abnormalities associated with APECED pneumonitis, we highlight the cellular and molecular basis of the autoimmune attack in the AIRE-deficient lung, and we provide a diagnostic and a therapeutic roadmap for patients with APECED pneumonitis. Beyond APECED, we discuss the relevance and potential broader applicability of these findings to other interstitial lung diseases seen in secondary AIRE deficiency states such as thymoma and RAG deficiency or in common polygenic autoimmune disorders such as idiopathic Sjögren’s syndrome.

scholarly journals Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome: Time to Review Diagnostic Criteria?

2003 ◽  
Vol 88 (7) ◽  
pp. 3146-3148 ◽  
Author(s):  
F. Buzi ◽  
R. Badolato ◽  
C. Mazza ◽  
S. Giliani ◽  
Lucia D. Notarangelo ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Novel Mutation ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Chronic Mucocutaneous Candidiasis ◽  
Biliary Cirrhosis ◽  
Mucocutaneous Candidiasis ◽  
Molecular Features ◽  
Autoimmune Polyendocrinopathy ◽  
Autoimmune Conditions

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive syndrome defined by two of the following conditions: chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison’s disease. Other autoimmune conditions may be associated, such as hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, chronic active hepatitis, pernicious anemia, vitiligo, alopecia, biliary cirrhosis, and ectodermal dysplasia. APECED is caused by mutations in the autoimmune regulator gene, mapping to 21q22.3. We report on three patients whose clinical and molecular features challenge the currently used diagnostic criteria for APECED. AR presented at 15 yr of age with a history of recurrent infections and mucocutaneous candidiasis. He is now 21 yr old, and no other signs or symptoms of APECED have appeared to date. DR presented at 7 yr of age with hypocalcemia and a prolonged Q-T interval on the electrocardiogram. He also had minor facial dysmorphisms and mild mental retardation. Serum calcium levels were low, PTH levels were undetectable, and hypoparathyroidism was therefore diagnosed. All other biochemical, immunological, and endocrinological tests were normal. DR is now 8 yr old with no other signs or symptoms of APECED. ST presented at 14 yr of age for alopecia aerata and pitted nail dystrophy and goiter. Thyroid function was normal in the presence of thyroid-specific antibodies. No other signs or symptoms of APECED have appeared to date. Genetic analysis revealed a typical mutation (R257X) on a single allele in both AP and DR; in ST, heterozygosity for a novel mutation (V484M) involving one of the zinc fingers of the plant homeodomain of the protein was found. The finding of a typical APECED mutation in two patients presenting with one isolated major clinical APECED feature and of a novel mutation in a patient presenting with atypical features of APECED onset suggests that the time might have come for updating the diagnostic criteria of this syndrome.

Sign in / Sign up

Export Citation Format

Share Document