Late diagnosis of chronic hypocalcemia due to autoimmune hypoparathyroidism

2021 ◽  
Vol 14 (6) ◽  
pp. e243299
Author(s):  
Maxime Teisseyre ◽  
Olivier Moranne ◽  
Sophie Renaud
Keyword(s):  
Calcium Supplementation ◽  
Genetic Disorder ◽  
Syndrome Type ◽  
Calcium Sensing Receptor ◽  
Basal Ganglia Calcification ◽  
Muscle Cramps ◽  
Oral Supplementation ◽  
Calcium Sensing ◽  
Autoimmune Polyendocrine Syndrome

Hypoparathyroidism is most often the result of postsurgical damage to the parathyroid glands but may occasionally be autoimmune hypoparathyroidism. In the latter context, activating antibodies directed against the calcium‐sensing receptor (CaSR) have been described. We hereby present the case of a patient suffering from chronic recurrent muscle cramps and paresthesia, presenting for a seizure due to hypocalcaemia. After eliminating the possibility of a genetic disorder, we searched for autoimmune hypoparathyroidism as there was no obvious cause of hypoparathyroidism. The search for anti-CaSR antibodies was positive. There was no argument for autoimmune polyendocrine syndrome type 1 so we concluded that it was isolated autoimmune hypoparathyroidism caused by activating antibodies to the CaSR. The patient was treated with vitamin D and calcium supplementation. The search for complications of hypoparathyroidism and hypercalciuria revealed basal ganglia calcification. The patient’s hypocalcaemia is now being kept under control with oral supplementation.

scholarly journals Activating Autoantibodies against the Calcium-Sensing Receptor Detected in Two Patients with Autoimmune Polyendocrine Syndrome Type 1

2009 ◽  
Vol 94 (12) ◽  
pp. 4749-4756 ◽  
Author(s):  
E. Helen Kemp ◽  
Nikos G. Gavalas ◽  
Kai J. E. Krohn ◽  
Edward M. Brown ◽  
Philip F. Watson ◽  
...  
Keyword(s):  
Inositol Phosphate ◽  
Autosomal Recessive Disorder ◽  
Syndrome Type ◽  
Calcium Sensing Receptor ◽  
Autoimmune Reaction ◽  
Aire Gene ◽  
Calcium Sensing ◽  
Autoimmune Polyendocrine Syndrome ◽  
Activating Autoantibodies

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) in parathyroid cells. Anti-CaSR binding antibodies have previously been detected in patients with APS1. Objective: The aim of this study was to determine whether anti-CaSR antibodies present in APS1 patients could modulate the response of the CaSR to stimulation by Ca2+. Results: The results indicated that two of the 14 APS1 patients included in the study had anti-CaSR antibodies that stimulated the receptor. These antibodies were detected by their ability to increase both Ca2+-dependent extracellular signal-regulated kinase phosphorylation and inositol phosphate accumulation in human embryonic kidney 293 cells expressing the CaSR. Conclusion: An important implication of the present results is that although the majority of APS1 patients do not have CaSR-stimulating antibodies, there may be a small but substantial minority of patients in whom the hypoparathyroid state is the result of functional suppression of the parathyroid glands rather than their irreversible destruction.

scholarly journals The Calcium-Sensing Receptor Is a Target of Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1

2007 ◽  
Vol 92 (6) ◽  
pp. 2107-2114 ◽  
Author(s):  
Nikos G. Gavalas ◽  
E. Helen Kemp ◽  
Kai J. E. Krohn ◽  
Edward M. Brown ◽  
Philip F. Watson ◽  
...  
Keyword(s):  
Patient Group ◽  
Autosomal Recessive Disorder ◽  
Syndrome Type ◽  
Calcium Sensing Receptor ◽  
Autoimmune Reaction ◽  
Calcium Sensing ◽  
Autoimmune Polyendocrine Syndrome ◽  
293 Cells ◽  
Receptor Antibodies

Abstract Context: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) on parathyroid cells. However, the detection of CaSR antibodies in APS1 remains controversial, with some studies disputing the relevance of the receptor as an autoantigen. Objective: The aim of this study was to analyze a defined set of APS1 patient sera for the presence of CaSR antibodies using different assay systems. Results: APS1 patients and individuals with other autoimmune disorders along with healthy subjects were tested for antibody binding to the CaSR. In an immunoprecipitation assay with the CaSR expressed in human embryonic kidney 293 cells, 12 of 14 (85.7%) APS1 and two of 28 (7.1%) Graves’ disease patients were considered positive for CaSR antibodies. The prevalence of receptor antibodies was significantly greater than that in the cohort of healthy individuals only in the APS1 patient group (P < 0.0001). In a flow cytometry assay, seven of 14 (50.0%) APS1 patient sera showed binding to the extracellular domain of the CaSR. The prevalence of receptor antibodies in the APS1 patient group was significantly greater than that in the group of healthy controls (P = 0.023). No CaSR antibodies could be detected in any patients or controls using a radiobinding assay. Conclusion: The CaSR is an autoantigen in APS1, but detection of antibodies against the receptor appears to be influenced by the assay system used.

scholarly journals Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series

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.

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

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.

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

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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