Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune manifestations have long been perceived as paradoxical in patients with primary immune deficiencies (PID). However, a defect in the mechanisms of control of self-reactive B and T cells may favour these manifestations. Three PID are defined by the occurrence of autoimmune manifestations: APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), autoimmune lymphoproliferative syndrome (ALPS) and IPEX syndrome (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In these conditions, organ specific autoimmune diseases such as type 1 diabetes mellitus or Hashimoto's thyroiditis are prominently encountered. Several other PID such as common variable immunodeficiency (CVID), Good syndrome and hyper-IgM syndrome are associated with a wide variety of autoimmune manifestations, mainly autoimmune cytopenias. Thus, autoimmune manifestations have been reported in 22% of patients with CVID, increasing to 50% in the subgroup of patients with systemic granulomatosis. Complement deficiencies involving components of the classical pathway are associated with systemic lupus erythematosus (SLE). Homozygous C2 deficiency, which is the most frequent hereditary deficiency in complement classical pathway components, is associated with SLE in 10% of the cases. Complete C1q and C4 deficiencies are less frequent but associated with a higher prevalence of SLE.
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PMID:Autoimmune manifestations in primary immune deficiencies. 1902 7

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder typically presenting with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal failure variably accompanied by other symptoms. APECED is caused by a mutation in the autoimmune regulator gene (AIRE). Today over 60 different mutations are known world-wide, most of them localized in exons 2, 8, and 10. We report here a German girl with rheumatoid factor positive arthritis, chronic mucocutaneous candidiasis, autoimmune hepatitis, chronic diarrhea, vitiligo, hypothyroidism, hypoparathyroidism, and adrenal failure who is homozygous for a novel mutation at the end of exon 3 of the AIRE gene (c.462G>A), within the conserved splice donor sequence. This mutation probably introduces a frameshift after amino acid 154 (p.Pro154fs) by skipping exon 4. In addition, we analyzed five other family members out of three generations for the AIRE gene mutation and for polymorphisms in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene region and lymphoid protein tyrosine phosphatase (PTPN22) gene, which are associated with the occurrence of sporadic autoimmune Addison's disease, type 1 diabetes mellitus, and generalized vitiligo.
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PMID:Novel homozygous AIRE mutation in a German patient with severe APECED. 1920 22

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.
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PMID:Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians. 1980 39

Autoimmune polyglandular syndromes (APS) are rarely diagnosed conditions characterised by the combination of two or more autoimmune endocrinopathies and nonendocrine autoimmunopathies. They comprise a wide spectrum of autoimmune disorders, differing in the immunologic features of their pathogenesis. Based on their clinical manifestation, APS are divided into four different types. Primary hypoparathyroidism is characteristic for APS type 1, the major disease components of which are adrenal insufficiency, hypoparathyroidism, and candidiasis. However, the literature is sparse regarding the presence of hypoparathyroidism in the remaining types of APS. In our article, we present a case of a young female with primary hypoparathyroidism and a family history of autoimmune disorders who after several years developed type 1 diabetes. She also had anti-transglutaminase and anti-parietal cell antibodies. This constellation of two endocrine disorders and non-endocrine abnormalities led to the diagnosis of APS type 4. We show in details diagnostic and treatment strategies undertaken in our patient and their impact on the course of APS.
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PMID:[Atypical clinical presentation of autoimmune polyglandular syndrome type 4]. 2203 74

Autoimmune polyglandular syndromes (APSs) include a cluster of autoimmune and nonautoimmune conditions which have been classified into subtypes. APSs type 1 is characterized by at least two of the following: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and autoimmune Addison's disease (AD). We report the chronological history of a female patient who presented with features most consistent with APS type 1, along with growth hormone deficiency and juvenile rheumatoid arthritis (JRA). In terms of her autoimmune diagnoses, she first presented with JRA at three years of age, then hypocalcemia and hypoparathyroidism at five years of age, type 1 diabetes (DM 1) at age eleven years, adrenal insufficiency at age fourteen years, recurrent mucocutaneous candidiasis as a teenager, growth hormone deficiency at age fourteen years leading to significant short stature, primary amenorrhoea, and hypogonadism, and finally alopecia at age twenty-six years. In addition to this, she has suffered other nonautoimmune medical problems including a Tetralogy of Fallot with a surgical repair at age six years. On review of the medical literature, we found no other previously reported case with this unique combination of medical problems.
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PMID:Growth hormone deficiency, short stature, and juvenile rheumatoid arthritis in a patient with autoimmune polyglandular syndrome type 1: case report and brief review of the literature. 2236 78

Autoimmune polyendocrine syndromes (APS) are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune diseases. APS comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS type 1) and a more common adult type with (APS 2) or without adrenal failure (APS 3). The first clinical manifestations of APS 1 usually occur in childhood whereas APS 2 mostly occurs during the third and fourth decades of life. The third type has been described in adults that, contrary to types 1 and 2, does not involve the adrenal cortex. No clinical differences between types 2 and 3 have been described except the absence of adrenal failure. Type 4 APS is a rare syndrome characterized by the combination of autoimmune conditions not falling into the above categories. It consists of adrenal failure with one or more minor autoimmune disorders barring major components of type 1 and 2 APS. Usually, autoimmune polyendocrine syndrome of adults manifests itself as one of the major autoimmune diseases (such as adrenal failure, Grave's disease, or type 1 diabetes) and minor autoimmune disorders (vitiligo, alopecia) preceding the development of autoimmune deficiency of major endocrine glands. This article describes a patient with type 3 APS, who developed type 1 diabetes. Grave's disease and vitiligo. The development of the syndrome started from vitiligo in the chidhood. Moreover, the patient suffered primary sterility and presented with progressive diabetic nephropathy of autoimmune origin. It is concluded that patients with a single autoimmune component of polyendocrine syndrome should be screened to exclude other autoimmune endocrine disorders.
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PMID:[Diagnostics and treatment of polyglandular syndrome of adults]. 2310 Dec 63

A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol. While antibodies against pancreatic glutamic acid decarboxylase (GAD) were strongly positive (7,690 U/ml), fasting glucose level was 4.9 mmol/L and HbA1c was 6.3% on admission. As GAD antibody showed a high-titer of >10,000 U/ml and fasting plasma glucose level showed a rising trend, we performed 75-g oral glucose tolerance test (OGTT) 6 years after discharge. Whereas OGTT in 2012 showed impaired glucose tolerance, glucose tolerance had reverted to normal in 2014. A patient with a high-titer GAD antibody does not always have progressive glucose intolerance. GAD antibody positivity is common in not only type 1 diabetes, but also APS I and stiff-person syndrome (SPS). There are differences in recognized epitopes among the three disorders. Epitopes for GAD65 antibody associated with type 1 diabetes are located in the middle region and the COOH-terminal of the GAD65 protein, whereas epitopes associated with SPS reside in the NH2-terminal in addition to the middle region and COOH-terminal. The present case suggests that these differences in epitopes may be related to various pathogenic mechanisms including glucose intolerance.
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PMID:A case of autoimmune polyendocrine syndrome type I with strong positive GAD antibody titer, followed up with glucose tolerance measured by oral glucose tolerance test. 2832 49


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