Autoimmune polyglandular syndrome type 1 and eye damage

Autoimmune polyendocrine syndrome type 1 (APS type 1) is a disease characterized by a variety of clinical manifestations resulting from the involvement of multiple endocrine and non-endocrine organs in the pathological process. APS type 1 is a rare genetically determined disease with autosomal recessive inheritance. Mutations in the autoimmune regulator gene (AIRE) lead to a disruption of the mechanism of normal antigen expression and the formation of abnormal clones of immune cells, and can cause autoimmune damage to organs. Within APS type 1, the most common disorders are primary adrenal insufficiency, hypoparathyroidism, and chronic candidiasis. Some understudied clinical manifestations of APS type 1 are autoimmune pathological processes in the eye: keratoconjunctivitis, dry eye syndrome, iridocyclitis, retinopathy, retinal detachment, and optic atrophy. This review presents the accumulated experimental and clinical data on the development of eye damage of autoimmune nature in APS type 1, as well as the laboratory and instrumental methods used for diagnosing the disease. Changes in the visual organs in combination with clinical manifestations of hypoparathyroidism, adrenal insufficiency and candidiasis should lead the clinical doctor to suspect the presence of APS type 1 and to examine the patient comprehensively. Timely genetic counselling will allow early identifi cation of the disease, timely prescription of appropriate treatment and prevention of severe complications.

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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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Autoimmune hepatitis as the first manifestation of autoimmune polyendocrine syndrome type 1 in a 5-year-old girl

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-4-101-108 ◽

2021 ◽

Vol 66 (4) ◽

pp. 101-108

Author(s):

E. A. Yablokova ◽

A. M. Rimskaya ◽

Yu. P. Grintsevich ◽

A. V. Vitebskaya ◽

E. V. Borisova ◽

...

Keyword(s):

Autoimmune Hepatitis ◽

Autoimmune Disorder ◽

Unknown Etiology ◽

Compound Heterozygous ◽

Chronic Mucocutaneous Candidiasis ◽

Syndrome Type ◽

Mucocutaneous Candidiasis ◽

Autoimmune Polyendocrine Syndrome ◽

Endocrine Organs

Autoimmune hepatitis is a chronic inflammatory liver disease of unknown etiology; the prevalence of juvenile autoimmune hepatitis is unknown. Autoimmune hepatitis occurs in 10–20% of patients with type 1 autoimmune polyendocrine syndrome, a rare (orphan) disease, which is characterized by a clinical triad in 70–100% of cases: chronic mucocutaneous candidiasis, hypopara thy roidismand adrenal insufficiency, as well as more 25 possible autoimmune endocrine and non-endocrine manifestations.Thisstudy describes a case of a 5-year-old girl with autoimmune hepatitis as the first clinical manifestation of the disease. The symptoms of chronic mucocutaneous candidiasis enabled us to suggest and genetically confirm the diagnosis of autoimmune poly endocrine syndrome type 1 before the lesions of endocrine organs. The girl had nonsense mutations R257 * and p.Q94* of the AIRE gene in a compound heterozygous state. Later, there appeared another autoimmune disorder – common vitiligo.Timelydiagnosisoftype1autoimmunepolyendocrinesyndromeinachildwiththefirstnon-endocrine autoimmune manifestation, initiation of therapy and further medical management made it possible to preventseve recomplications and improve the patient’s quality of life.

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

Endocrine Connections ◽

10.1530/ec-17-0022 ◽

2017 ◽

Vol 6 (5) ◽

pp. 289-296 ◽

Cited By ~ 8

Author(s):

Ghazala Zaidi ◽

Vijayalakshmi Bhatia ◽

Saroj K Sahoo ◽

Aditya Narayan Sarangi ◽

Niharika Bharti ◽

...

Keyword(s):

Clinical Features ◽

Genetic Heterogeneity ◽

Clinical Manifestations ◽

Gene Mutations ◽

Young Age ◽

Clinical Aspects ◽

Syndrome Type ◽

Autoimmune Polyendocrine Syndrome ◽

Organ Specific

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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Autoimmune polyendocrine syndrome type 1: case report and review of literature

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302012000100009 ◽

2012 ◽

Vol 56 (1) ◽

pp. 54-66 ◽

Cited By ~ 19

Author(s):

Fernanda Guimarães Weiler ◽

Magnus R. Dias-da-Silva ◽

Marise Lazaretti-Castro

Keyword(s):

Autosomal Recessive ◽

Clinical Course ◽

Clinical Manifestations ◽

Autosomal Recessive Disorder ◽

Syndrome Type ◽

Adrenal Failure ◽

Review Of Literature ◽

Autoimmune Polyendocrine Syndrome

Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.

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

BMJ Case Reports ◽

10.1136/bcr-2021-241680 ◽

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 .

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