Identification of autoimmune polyendocrine syndrome type 1 in patients with isolated hypoparathyroidism

Sahoo, Saroj Kumar; Zaidi, Ghazala; Srivastava, Rajeshwar Nath; Sarangi, Aditya Narayan; Bharti, Niharika; Eriksson, Daniel; Bensing, Sophie; Kämpe, Olle; Aggarwal, Amita; Aggarwal, Rakesh; Bhatia, Eesh

doi:10.1111/cen.13111

Cited by 14 publications

(4 citation statements)

References 36 publications

(175 reference statements)

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“…Second, patients with isolated hypoparathyroidism have been discovered with pathogenic biallelic AIRE mutations, raising the possibility of the existence of several unrecognized APECED patients with biallelic AIRE mutations who may develop isolated organ‐specific autoimmune manifestations that are typical of APECED syndrome but have not developed a classic diagnostic dyad to raise awareness for AIRE genetic testing. Third, in the North American APECED population, we have witnessed a significant proportion (~15%) that does not have biallelic AIRE mutations or deletions and yet, the clinical presentation of the patients is indistinguishable from patients with biallelic AIRE mutations .…”

Section: Aire Mutations In Apeced Patientsmentioning

confidence: 99%

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

Constantine

Lionakis

2018

Immunological Reviews

128

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Summary: The discovery of the Autoimmune Regulator (AIRE) protein and the delineation of its critical contributions in the establishment of central immune tolerance has significantly expanded our understanding of the immunological mechanisms that protect from the development of autoimmune disease. The parallel identification and characterization of patient cohorts with the monogenic disorder Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), which is typically caused by biallelic AIRE mutations, has underscored the critical contribution of AIRE in fungal immune surveillance at mucosal surfaces and in prevention of multiorgan autoimmunity in humans. In this review, we synthesize the current clinical, genetic, molecular and immunological knowledge derived from basic studies in Aire-deficient animals and from APECED patient cohorts. We also outline major advances and research endeavors that show promise for informing improved diagnostic and therapeutic approaches for patients with APECED.

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Section: Aire Mutations In Apeced Patientsmentioning

confidence: 99%

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

Constantine

Lionakis

2018

Immunological Reviews

128

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“…In addition to AIRE mutations, socio-economic and environmental factors may affect the clinical spectrum and prognosis of the disorder. There is currently little information on APS1 in Indian patients (18, 19, 20, 21). In an earlier study of nine Indian patients, we described five different AIRE mutations, of which two were novel (20).…”

Section: Introductionmentioning

confidence: 99%

Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

Zaidi

Bhatia

Sahoo

et al. 2017

Endocrine Connections

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ObjectiveAutoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.DesignTwenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.MethodsClinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.ResultsPatients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.ConclusionsIndian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

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“…Another report from the United States included data on postsurgical hypoparathyroidism, whereas we restricted our data to SIHP only . SIHP is commonly seen in the paediatric age group in association with the autoimmune disorders . The mean age of participants and patients with a diagnosis of parathyroid disorders was not different in our data ( P =.1063).…”

Section: Discussionmentioning

confidence: 71%

Incidence of parathyroid disorders in Indian adult male population: A 25‐year follow‐up study

Kumar

Patnaik

2017

Clinical Endocrinology

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Identification of autoimmune polyendocrine syndrome type 1 in patients with isolated hypoparathyroidism

Abstract: Eight percentage of patients with isolated HP had elevated IFN-α antibody levels and AIRE mutation-positive APS1. All APS1 patients had atypical clinical features. Testing for IFN-α antibody should be considered in patients with idiopathic HP.

Cited by 14 publications

References 36 publications

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

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

Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

Incidence of parathyroid disorders in Indian adult male population: A 25‐year follow‐up study

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