scholarly journals Hypoadrenalism as the Single Presentation of Autoimmune Polyglandular Syndrome Type-1

2021 ◽  
Author(s):  
Nadim H Nasser ◽  
Nadra G  Samra ◽  
Deeb D Naccache
Keyword(s):  
Similar Case ◽  
Case Reports ◽  
Addison’S Disease ◽  
Hereditary Disease ◽  
Addison's Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Autoimmune Polyglandular Syndrome ◽  
Single Presentation ◽  
Autoimmune Polyglandular Syndrome Type

Abstract Type-1 autoimmune polyglandular syndrome (APS1) is a rare hereditary disease affecting nearly 600 patients worldwide. The first of its cardinal manifestations, chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HPT), or Addison’s disease (AD), presents in childhood. Additional non-classical landmarks of APS1 continue to develop as late as the fifth decade of life. Two-thirds of patients develop the full triad before 25 years of age. Only 20% of patients develop the entire triad simultaneously. Addison's disease is rarely reported as the first manifestation.According to APS1 classifications, restricted criteria for a single cardinal component, although elements of suspicion are not sufficient to diagnose APS1.This case report is peculiar as hypoadrenalism was the first and only manifestation of APS1 for nearly three decades since its diagnosis. Theoretically, exceptions from the protocol of APS1 diagnostic criteria would be recognized as acceptable for diagnosis in the future, when similar case reports of only one component of APS1 appear.

scholarly journals Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberto Perniola ◽  
Alessandra Fierabracci ◽  
Alberto Falorni
Keyword(s):  
Specific Antigen ◽  
Addison’S Disease ◽  
The Self ◽  
Current Evidence ◽  
Addison's Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Autoimmune Polyglandular Syndrome Type

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.

scholarly journals Hypoparathyroidism as the single major component for decades of autoimmune polyglandular syndrome type 1

2020 ◽  
Vol 2020 ◽  
Author(s):  
Joana Lima Ferreira ◽  
Francisco Simões de Carvalho ◽  
Ana Paula Marques ◽  
Rosa Maria Príncipe
Keyword(s):  
Addison’S Disease ◽  
Clinical History ◽  
Addison's Disease ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Autoimmune Polyglandular Syndrome Type ◽  
High Index Of Suspicion

Summary Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison’s disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison’s disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex. Learning points: Autoimmune polyglandular syndrome type 1 (APS-1) is a deeply heterogeneous genetic entity with a broad spectrum of clinical manifestations and a significant intra-family phenotypic variability. Early diagnosis of APS-1 is challenging but clinically relevant, as endocrine and non-endocrine manifestations may occur during its natural history. APS-1 should be considered in cases of acquired hypoparathyroidism, and even more so with manifestations with early onset, family history and consanguinity. APS-1 diagnosis needs a high index of suspicion. Key information such as all the comorbidities and family aspects would never be valued in the absence of a complete clinical history taking. Especially in hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex and is not a matter of simply approaching individually each condition. Regular long-term monitoring of APS-1 is essential. Intercalary contact by phone calls benefits the control of the disease and the management of complications.

scholarly journals Report of two siblings with APECED in Serbia: is there a founder effect of c.769C>T AIRE genotype?

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Alessandra Fierabracci ◽  
Mariafrancesca Lanzillotta ◽  
Ivana Vorgučin ◽  
Alessia Palma ◽  
Dragan Katanić ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Founder Effect ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Genetic Characteristics ◽  
Autoimmune Polyglandular Syndrome ◽  
Autoimmune Conditions ◽  
Autoimmune Polyglandular Syndrome Type ◽  
Classical Triad

Abstract Background Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) or autoimmune polyglandular syndrome Type 1 is a rare autosomal recessive syndrome. The disorder is caused by mutations in the AIRE (AutoImmune Regulator) gene. According to the classic criteria, clinical diagnosis requires the presence of at least two of three main components: chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Furthermore, patients are often affected by other endocrine or non-endocrine associated autoimmune conditions. The enrichment of the non-classical triad seems to occur differently in different cohorts. Screenings of the population revealed that homozygous AIRE mutations c.769C > T, c.415C > T and c.254A > G have a founder effect in Finnish, Sardinian and Iranian Jew populations respectively. Case presentation We report here the clinical and genetic characteristics of two new Serbian APECED siblings, one male and one female, actual age of 27 and 24 respectively, born from non-consanguineous parents. Addison’s disease was diagnosed in the male at the age of 3.5 and hypoparathyroidism at the age of 4. The female developed hypoparathyroidism at 4 years of age. She presented diffuse alopecia, madarosis, onychomycosis, teeth enamel dysplasia. She further developed Addison’s disease at the age of 11 and Hashimoto’s thyroiditis at the age of 13.5. She had menarche at the age of 14 but developed autoimmune oophoritis and premature ovarian failure at the age of 16. A treatment with hydrocortisone, fludrocortisone and alfacalcidiol was established for both siblings; L-T4 (levo-thyroxine) for thyroid dysfunction and levonorgestrel and etinilestradiol for POF were also administered to the female. Genetic screening revealed a homozygous c.769C > T (R257X (p.Arg257X)) AIRE mutation. We additionally reviewed the literature on 11 previously published Serbian patients and evaluated the frequency of their main diseases in comparison to Finnish, Sardinian, Turkish, Indian and North/South American cohorts. Conclusion A founder effect was discovered for the R257X genotype detected in the DNA of 10 homozygous and 2 heterozygous patients. Of note, all Serbian APECED patients were affected by adrenal insufficiency and 10 out of 13 patients presented CMC.

Atypical presentation of autoimmune polyglandular syndrome type 1 in the fifth decade

2021 ◽  
Vol 14 (4) ◽  
pp. e241680
Author(s):  
Aditya Sanjeevi ◽  
Adlyne Reena Asirvatham ◽  
Karthik Balachandran ◽  
Shriraam Mahadevan
Keyword(s):  
Adrenal Insufficiency ◽  
Vitamin D Supplementation ◽  
Chronic Mucocutaneous Candidiasis ◽  
Syndrome Type ◽  
Primary Amenorrhoea ◽  
Autoimmune Polyglandular Syndrome ◽  
Nail Changes ◽  
History Of ◽  
Autoimmune Polyglandular Syndrome Type

A 45-year-old woman presented to us with a short-term history of nausea, vomiting and giddiness. On arrival at our hospital, examination revealed postural hypotension. Fluid resuscitation with intravenous normal saline was commenced. She also had chronic mucocutaneous candidiasis and nail changes suggestive of ectodermal dystrophy. Detailed history taking revealed that she had never attained menarche. Serum biochemistries showed hyponatraemia, hyperkalaemia, and hypocalcaemia (sodium, 127 mEq/L; potassium, 6 mEq/L; and albumin-corrected calcium, 6 mg/dL). Adrenocorticotropic hormone-stimulated cortisol (16.7 mcg/dL) was suboptimal favouring adrenal insufficiency. She was started on hydrocortisone and fludrocortisone supplementation. Additionally, the parathyroid hormone was inappropriately low (3.8 pg/mL) confirming hypoparathyroidism. Oral calcium and active vitamin D supplementation were added. With the above clinical and biochemical picture, namely, clustering of primary amenorrhoea, adrenal insufficiency and hypoparathyroidism, the diagnosis pointed towards autoimmune polyglandular syndrome. Genetic workup revealed a deletion in exon 8 of the autoimmune regulator gene confirming the diagnosis of autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy/autoimmune polyglandular syndrome type 1 .

scholarly journals Autoimmune Polyglandular Syndrome Type 1

2012 ◽  
Vol 2 ◽  
pp. 62 ◽  
Author(s):  
Vedeswari C. Ponranjini ◽  
S Jayachandran ◽  
L Kayal ◽  
K Bakyalakshmi
Keyword(s):  
Oral Candidiasis ◽  
The Body ◽  
Chronic Mucocutaneous Candidiasis ◽  
Enamel Hypoplasia ◽  
Autoimmune Polyglandular Syndrome ◽  
Aire Gene ◽  
History Of ◽  
Autoimmune Polyglandular Syndrome Type ◽  
Individual Disease

Autoimmune Polyglandular Syndrome (APS) Type 1 is a rare hereditary disorder that damages organs in the body. This disease entity is the result of a mutation in the AIRE gene. It is characterized by three classic clinical features - hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. For a patient to be diagnosed as having APS Type 1 syndrome at least two of these features needs to be present. The third entity may develop as the disease progresses. We report a case of a 35-year-old female patient with a history of seizure from the age of 11 years, who was managed with anticonvulsant drugs. With worsening of the seizure episodes, patient was diagnosed to have hypoparathyroidism together with the manifestations of oral candidiasis, nails dystrophy, enamel hypoplasia, and hypogonadism. A diagnosis of APS-1 was considered. The facility for genetic analysis of the AIRE gene mutation was not accessible, as the test costs were prohibitive and not affordable for the patient. Patient management was directed to treating individual disease components. However, cerebral and dental changes were irreversible.

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.

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