Novel Autoimmune Polyendocrine Syndrome: Adult Combined GH, Prolactin and TSH Deficiency Associated with Circulating PIT-1 Antibody

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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Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure

Acta Endocrinologica ◽

10.1530/eje-09-0231 ◽

2009 ◽

Vol 161 (1) ◽

pp. 179-187 ◽

Cited By ~ 75

Author(s):

Anne Bachelot ◽

Agnès Rouxel ◽

Nathalie Massin ◽

Jérome Dulon ◽

Carine Courtillot ◽

...

Keyword(s):

Premature Ovarian Failure ◽

Chromosomal Abnormalities ◽

Phenotypic Variability ◽

Genetic Data ◽

Ovarian Failure ◽

Mineral Density ◽

Genetic Studies ◽

Autoimmune Polyendocrine Syndrome ◽

Design And Methods

ObjectivePremature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis.Design and methodsWe performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center.ResultsSeventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1.ConclusionA genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

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