Autoimmune polyglandular syndrome type 1 with diabetes insipidus: a case report

Abstract Background Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic inherited disease caused by mutations of the autoimmune regulator gene (AIRE). The three major components of this syndrome are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical insufficiency. Case presentation We report a 20-year-old male who was clinically diagnosed with APS-1 at the age of 15. He was admitted to our department this time for suffering from polyuria and polydipsia for 6 months and was finally diagnosed with diabetes insipidus. Whole-exome sequencing (WES) revealed a novel compound heterozygous mutation of the AIRE gene —the c.239 T > G (p.Val80Gly) variant on one allele and the copy number variant (CNV) of 21q22.3(chr21:45,670,150–45,706,528)*1 on the other. Conclusions This case suggests that diabetes insipidus is a rare component of APS-1 and expands the variety of mutations on AIRE gene.

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A novel compound heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrine syndrome type 1

Annals of Pediatric Endocrinology & Metabolism ◽

10.6065/apem.2019.24.4.248 ◽

2019 ◽

Vol 24 (4) ◽

pp. 248-252

Author(s):

Junghwan Suh ◽

Han Saem Choi ◽

Ahreum Kwon ◽

Hyun Wook Chae ◽

Jin-Sung Lee ◽

...

Keyword(s):

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Syndrome Type ◽

Aire Gene ◽

Autoimmune Polyendocrine Syndrome

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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: an Italian survey on 158 patients

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01585-6 ◽

2021 ◽

Author(s):

S. Garelli ◽

M. Dalla Costa ◽

C. Sabbadin ◽

S. Barollo ◽

B. Rubin ◽

...

Keyword(s):

Gene Mutations ◽

Premature Menopause ◽

Chronic Mucocutaneous Candidiasis ◽

Syndrome Type ◽

Inherited Disease ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Polyendocrine Syndrome ◽

Autoimmune Conditions

Abstract Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

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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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A compound heterozygous mutation in the BSND gene detected in Bartter syndrome type IV

Pediatric Nephrology ◽

10.1007/s00467-005-2091-6 ◽

2005 ◽

Vol 21 (2) ◽

pp. 190-193 ◽

Cited By ~ 11

Author(s):

Sachiko Kitanaka ◽

Utako Sato ◽

Kenichi Maruyama ◽

Takashi Igarashi

Keyword(s):

Bartter Syndrome ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Syndrome Type ◽

Type Iv

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1080 ◽

2009 ◽

Vol 94 (12) ◽

pp. 4749-4756 ◽

Cited By ~ 55

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.

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Compound Heterozygous Mutation of Aquaporin 2 Gene in Woman Patient with Congenital Nephrogenic Diabetes Insipidus

Internal Medicine ◽

10.2169/internalmedicine.48.1642 ◽

2009 ◽

Vol 48 (6) ◽

pp. 437-440 ◽

Cited By ~ 1

Author(s):

Zenta Tsutsumi ◽

Taku Inokuchi ◽

Daisuke Tamada ◽

Yuji Moriwaki ◽

Tsuneyoshi Ka ◽

...

Keyword(s):

Diabetes Insipidus ◽

Nephrogenic Diabetes Insipidus ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Woman Patient ◽

Aquaporin 2 ◽

Congenital Nephrogenic Diabetes Insipidus

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Spinal Muscular Atrophy With Respiratory Distress Type 1—A Child With Atypical Presentation

Child Neurology Open ◽

10.1177/2329048x18769811 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1876981 ◽

Cited By ~ 1

Author(s):

Annie Ting Gee Chiu ◽

Sophelia Hoi Shan Chan ◽

Shun Ping Wu ◽

Shun Hin Ting ◽

Brian Hon Yin Chung ◽

...

Keyword(s):

Respiratory Distress ◽

Spinal Muscular Atrophy ◽

Heart Surgery ◽

Muscular Atrophy ◽

Cerebral Atrophy ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Sensorimotor Polyneuropathy

The authors report a child with spinal muscular atrophy with respiratory distress type 1 (SMARD1). She presented atypically with hypothyroidism and heart failure due to septal defects that required early heart surgery and microcephaly in association with cerebral atrophy and thin corpus collosum. The subsequent asymmetrical onset of diaphragmatic paralysis, persistent hypotonia, and generalized muscle weakness led to the suspicion of spinal muscular atrophy with respiratory distress type 1. Sanger sequencing confirmed a compound heterozygous mutation in the Immunoglobulin Mu Binding Protein 2 (IGHMBP2) gene, with a known mutation c.2362C > T (p.Arg788*) and a novel frameshift mutation c.2048delG (p.Gly683A1afs*50). Serial nerve conduction study and electromyography confirmed progressive sensorimotor polyneuropathy and neuronopathy. In summary, this case report describes a child with spinal muscular atrophy with respiratory distress type 1 also with congenital cardiac disease and endocrine dysfunction, expanding the phenotypic spectrum of this condition. A high index of suspicion is needed in diagnosing this rare condition to guide the management and genetic counseling.

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