The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers

Objective Autoimmune 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. Design Twenty-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. Methods Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Results Patients 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. Conclusions Indian 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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Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01933-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ya-Bing Wang ◽

Ou Wang ◽

Min Nie ◽

Yan Jiang ◽

Mei Li ◽

...

Keyword(s):

Case Series ◽

Pure Red Cell Aplasia ◽

Hereditary Disease ◽

Chinese Patients ◽

Chronic Mucocutaneous Candidiasis ◽

Syndrome Type ◽

Myeloproliferative Disease ◽

College Hospital ◽

Autoimmune Polyendocrine Syndrome

Abstract Background Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital. Results In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison’s disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1. Conclusion We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.

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Acquired pure red cell aplasia and T cell large granular lymphocytic leukaemia in patients with autoimmune polyglandular syndrome type 1

BMC Medical Genomics ◽

10.1186/s12920-020-00866-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jing Ruan ◽

Xuan Wang ◽

Xianyong Jiang ◽

Miao Chen

Keyword(s):

Lymphocytic Leukaemia ◽

Pure Red Cell Aplasia ◽

Chronic Diarrhoea ◽

Syndrome Type ◽

Red Cell ◽

Recurrent Pneumonia ◽

Red Cell Aplasia ◽

Autoimmune Polyendocrine Syndrome ◽

Immunological Mechanisms

Abstract Background Pure red cell aplasia (PRCA) and large granular lymphocytic leukaemia (LGLL) are very rare complications of autoimmune polyendocrine syndrome type 1 (APS1). Here, we report a case of APS1 with PRCA and LGLL. Previous cases were reviewed, and possible mechanisms are discussed. Case presentation A 31-year-old female presented with anaemia and was diagnosed with PRCA in our centre. She also had hypoparathyroidism for 24 years, premature ovarian failure for 10 years, osteoporosis for 5 years, recurrent pneumonia with bronchiectasis for 4 years and chronic diarrhoea for 1 year. Boosted whole-exome analysis showed AIRE heterozygous mutations, confirming the diagnosis as APS1. LGLL was diagnosed during follow-up. The PRCA responded well to glucocorticoid. treatment Conclusion AIRE is causally related to the development of LGLL and consequent PRCA, which may be due to some immunological mechanisms.

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Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections

Clinical Immunology ◽

10.1016/j.clim.2021.108851 ◽

2021 ◽

Vol 231 ◽

pp. 108851

Author(s):

Iivo Hetemäki ◽

Saila Laakso ◽

Hannamari Välimaa ◽

Iivari Kleino ◽

Eliisa Kekäläinen ◽

...

Keyword(s):

Syndrome Type ◽

Autoimmune Polyendocrine Syndrome ◽

Increased Susceptibility

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Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1

The Journal of the Royal College of Physicians of Edinburgh ◽

10.4997/jrcpe.2015.210 ◽

2015 ◽

Vol 45 (2) ◽

pp. 136-140 ◽

Cited By ~ 1

Author(s):

R Sinha ◽

AR Chapman ◽

GT Reid ◽

PC Hayes

Keyword(s):

Fulminant Hepatic Failure ◽

Hepatic Failure ◽

Syndrome Type ◽

Autoimmune Polyendocrine Syndrome

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A case of late manifestation of primary adrenal insufficiency in the autoimmune polyglandular syndrome type 1

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2019-47-017 ◽

2019 ◽

Vol 47 (2) ◽

pp. 175-179

Author(s):

V. V. Troshina ◽

T. A. Grebennikova ◽

Zh. E. Belaya

Keyword(s):

Adrenal Insufficiency ◽

Clinical Case ◽

Clinical Symptoms ◽

Syndrome Type ◽

Primary Adrenal Insufficiency ◽

Autoimmune Polyglandular Syndrome ◽

Autoimmune Polyendocrine Syndrome ◽

Autoimmune Polyglandular Syndrome Type ◽

Timely Treatment

The article describes a clinical case of primary adrenal insufficiency which manifested at an atypically advanced age. Primary adrenal insufficiency combined with other clinical symptoms suggested the autoimmune polyendocrine syndrome type 1. Subsequently, the diagnosis was confirmed by the results of genetic testing. The particulars of the clinical case include the age of patient at manifestation of the disease (49 years). The lack of treatment resulted in dramatic clinical decompensation. This clinical case is intended to draw clinicians' attention to the necessity of detection of primary adrenal insufficiency and appropriate and timely treatment. Taking into account eventual diagnostic problems, it is necessary to raise awareness about this disease among practicing doctors of various specialties.

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