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)

Coeliac disease is an autoimmune disorder, characterised by villous atrophy of the small intestine, which results from a T-cell-mediated response to gluten-derived peptides. The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is involved in the regulation of T-cell activation and the CTLA4 +49 A/G polymorphism in exon 1 has been implicated in several autoimmune disorders, including coeliac disease. However, this polymorphism was recently excluded as being the causal variant in Graves' disease, autoimmune hypothyroidism and type I diabetes mellitus. This causal variant was mapped to the 3' region of CTLA4, with the CT60 polymorphism showing the strongest association. The aim of this study was to determine the role of the CTLA4 gene in coeliac disease in the Dutch population. The +49 A/G and CT60 polymorphisms were genotyped in a case-control cohort of 215 patients and controls. The frequency of the +49 G-allele was increased in cases, although not significantly. However, the frequency of the CT60 G-allele was increased with borderline significance in coeliac disease patients (P = 0.048), although the genotype distributions did not show a significant difference between cases and controls. These results indicate the involvement of the CTLA4 gene in coeliac disease development. The haplotype carrying the CT60 G-allele was shown to be associated with lower mRNA levels of the soluble CTLA-4 isoform, providing a possible mechanism for the T-cell-mediated destruction of the small intestine.
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PMID:CTLA4 +49 A/G and CT60 polymorphisms in Dutch coeliac disease patients. 1519 80

The autoimmune polyglandular syndrome (APS) is characterized by a variable coexistence of several autoimmune diseases, affecting predominantly endocrine glands. In general two types of APS are distinguished. Type 1 APS is an autosomal recessive disorder often leading to insufficiency of the adrenal cortex, the parathyroid glands, and/or the gonads. This type of APS often affects the skin in form of chronic mucocutaneous candidiasis and ectodermal dystrophies (vitiligo, alopecia, keratopathy, dystrophy of dental enamel and nails). The second form of APS is a polygenic disease which usually involves the adrenal gland, the thyroid and the pancreatic beta-cells. In rare cases APS type 2 is associated with myasthenia gravis, autoimmune thrombocytopenic purpura, Sjogren's syndrome or rheumatoid arthritis. Here we describe a case of APS with the unusual combination of type 1 diabetes, secondary adrenocortical insufficiency, growth hormone deficiency, and primary hypothyroidism associated with lethal idiopathic giant cell myocarditis. The combination of APS and idiopathic giant cell myocarditis which is a rare, frequently fatal autoimmune disorder of myocardium affecting most commonly young individuals has not been reported so far.
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PMID:Autoimmune polyglandular syndrome associated with idiopathic giant cell myocarditis. 1592 18

The cytotoxic T lymphocyte antigen 4 (CTLA4) acts as a potent negative regulator of T-cell response, and has been suggested as a pivotal candidate gene for autoimmune disorders such as Graves' disease, type 1 diabetes and autoimmune hypothyroidism, among others. Several single-nucleotide polymorphisms (SNPs) have been proposed as the susceptibility variants, or to be in strong linkage disequilibrium (LD) with the variant. Nevertheless, contradictory results have been found, which may be due to lack of knowledge of the genetic structure of CTLA4 and its geographic variation. We have typed 17 SNPs throughout the CTLA4 gene region in order to analyze the haplotype diversity and LD structure in a worldwide population set (1262 individuals from 44 populations) to understand the variation pattern of the region. Allele and haplotype frequency differentiation between populations is consistent with genomewide averages and points to a lack of strong population-specific selection pressures. LD is high and its pattern is not significantly different within or between continents. However, haplotype composition is significantly different between geographical groups. A continent-specific set of haplotype tagging SNPs has been designed to be used for future association studies. These are portable among populations, although their efficiency might vary depending on the population haplotype spectrum.
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PMID:Haplotype tagging efficiency in worldwide populations in CTLA4 gene. 1603 71

Multiple sclerosis (MS) occurs with immune-mediated mechanisms, but its pathogenesis is not accurately known. The coexistence of MS with other autoimmune diseases has been reported. The hypothesis that MS coexists with other autoimmune diseases has been supported by the reported association of MS with type I diabetes mellitus and inflammatory disorders. Even though there have been only rare reports of associations between Hashimoto thyroiditis and MS, this association is important for its clinical and therapeutic aspects. Proximal muscle weakness, myalgia, and fatigue are symptoms that are common in both MS and hypothyroidism. When MS patients demonstrate these symptoms, thyroid function tests should be performed. The thyroid hormone levels of MS patients being treated with interferon-beta and Campath-1H also should be monitored. The authors report the clinical data of 2 definite MS patients who also fulfilled criteria for Hashimoto thyroiditis.
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PMID:Multiple sclerosis and Hashimoto thyroiditis: two cases. 1614 37

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare inborn error of immune regulation characterized by the early onset of one or more autoimmune diseases in boys. IPEX is caused by mutations in FOXP3, and is thus the homologue of the scurfy mutant mouse. The gene product, Scurfin, is required for the development of CD4+CD25+ T regulatory cells. In the absence of T regulatory cells, activated CD4+ T cells instigate multi-organ damage resulting in type 1 diabetes, enteropathy, eczema, hypothyroidism, and other autoimmune disorders. While effective therapies are currently limited, studies in the scurfy mouse are revealing aspects of pathophysiology and genetics that will lead to novel approaches for treating IPEX and other autoimmune disorders. Females carrying Foxp3 mutations are unaffected. In new experiments we show that female scurfy mice that are also heterozygous in trans for the X-linked recessive common gamma chain knockout contract autoimmune disease, proving that murine Foxp3 is subject to X-inactivation and providing an example of gene-gene interaction causing autoimmune disease in females. One explanation for the lesser disease severity in these females is proposed.
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PMID:IPEX and FOXP3: clinical and research perspectives. 1624 87

A 55-year-old man who was diagnosed as having type 1 diabetes mellitus (DM) at the age of 50 years was started on insulin therapy. At 54 years old of age, he suddenly developed complex partial seizures, which frequently occurred despite intensive anti-epileptic drug therapy. Neurological examination on admission revealed hyporeflexia in bilateral upper and lower extremities without any muscle rigidity, painful spasm or cerebellar ataxia. Laboratory examination showed poor glycemic control with increased glycated hemoglobin levels. Positive anti-thyroglobulin antibodies and anti-thyroid peroxidase (TPO) antibodies and slight elevation of TSH levels are consistent with subclinical hypothyroidism due to Hashimoto's thyroiditis. A high titer of anti-glutamic acid decarboxylase (GAD) antibodies was detected in the patient's serum and cerebrospinal fluid (CSF). Electroencephalography showed temporal spikes, consistent with complex partial seizure. This is a very rare case presenting with concomitant type 1 diabetes and drug-resistant epilepsy associated with high titers of circulating and CSF anti-GAD antibodies.
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PMID:Type 1 diabetes mellitus and drug-resistant epilepsy: presence of high titer of anti-glutamic acid decarboxylase autoantibodies in serum and cerebrospinal fluid. 1635 56

Hashimoto's Thyroiditis (HT) is the most common cause of thyroid diseases in children and adolescents and it is also the most common cause of acquired hypothyroidism with or without goiter. The linkage between HT and some HLA genes has been reported and a genetic predisposition to thyroid autoimmunity is suggested by observations in twins. There is no direct evidence that infections cause HT in humans, while iodine and iodine containing drugs can precipitate HT in susceptible populations. There is an infiltration of lymphocytes and plasma cells between the follicles followed by their atrophy. The clinical course is variable and spontaneous remission may occur in adolescence. Goiter, menstrual disorders, short stature, constipation, nervousness and exophthalmos have been reported as the most recurrent clinical features of HT. Nevertheless we studied 33 patients with HT, 22 girls and 11 boys aged 4.9-19 years and most of them were euthyroid clinically. Hashimoto thyroiditis is often associated with type 1 diabetes and other autoimmune disorders such as coeliac disease, type 2 and type 3 polyglandular autoimmune disorders. Girls with Turner syndrome may develop HT. Patients with HT have positive antibodies to thyroglobulin and/or to thyroperoxidase in blood. Thyroid function could be normal or abnormal (overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism). Abnormal ultrasound patterns may be present in patients with HT disease as diffuse hypoechogenicity and pseudonodules. L-thyroxine therapy is indicated in HT with hypothyroidism, but periodic re-evaluations are required because HT could be a self-limited disorder in some cases.
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PMID:Hashimoto's Thyroiditis. 1644 60

Two hundred and seventy-three patients with thalassaemia major (TM) were followed in the Ferrara Thalassaemia Centre over a thirty-year period. Forty-two patients had insulin dependent diabetes mellitus (IDDM). The first case was diagnosed in 1973. The incidence of IDDM peaked in 1986 (3.9%), and it was 0.7% at the time of the study (March 1998). The prevalence of IDDM increased progressively over time, reaching 14.2% in 1998. Mean age at diagnosis of IDDM was 18.2 -/+ 3.6 years and this also rose significantly during the study period (p<0.01). Hypogonadism was present in 91% of patients with IDDM, hypothyroidism in 68%, hypoparathyroidism in 21%, and cardiopathy in 69%, all significantly more prevalent than in patients without IDDM. These complications appeared with the same frequency before and after the diagnosis of IDDM. Survival of patients with and without IDDM was similar and no difference in the primary cause of death was found between the two groups. Main risk factors associated with IDDM were poor compliance with desferioxamine (DFO) treatment (p<0.05%), advanced age at the start of intensive chelation therapy (p<0.001), liver cirrhosis or severe fibrosis (p<0.0001, odds ratio 9.5, CI 95% 2.8-32.6). Prevalence of impaired glucose tolerance (IGT) was highest in 1981, 1984, and 1985 when the incidence of IDDM was increasing; in 1995 the prevalence of IGT in patients aged 16-20 years was lower in comparison with that observed in 1975 (17% vs. 59%, p<0.01). Risk factors associated with IGT were: male sex (p<0.05), poor compliance with DFO therapy (p<0.05) and liver iron concentration 4 times above the normal value. In conclusion, our longitudinal study confirms that the incidence of IDDM and prevalence of IGT have been decreasing over the course of the last decade, appearing at a more advanced age, although some differences have not reached statistical significance. Iron overload and liver disease were the main associated risk factors, while positive family history for diabetes did not influence glucose metabolism in our patients.
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PMID:Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. 1646 13

We present a case of a 69 year old female with autoimmune polyglandular syndrome type 2 or Schmidt's syndrome. The syndrome consists of primary autoimmune adrenocortical insufficiency (Addison's disease), autoimmune hypothyroidism, and type 1 diabetes. In the presented case Addison's disease was diagnosed on the basis of clinical symptoms, low serum cortisol level: at 8 am 129,1 nmol/l (reference range 220,70-689,70), and high ACTH level: 1540,8 pg/ml (reference range 0-50). Hypothyroidism was diagnosed with serum TSH of 4,46 microU/ml (rr 0,20-3,50), aTPO antibodies titer was 117 U/ml (rr 0-60). The patient also presented insulin dependent diabetes treated with insulin and osteoporosis with a compressive vertebral fracture and a hip fracture in the past (hip T-score = -2,62). After substitutional pharmacotherapy was implemented, the patient was discharged in good health. Possible correlation between bone metabolism disorders and autoimmune polyglandular syndrome needs further investigation.
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PMID:[Autoimmune polyglandular syndrome type 2 and osteoporosis in a 69 years old patient]. 1673 4

Turner syndrome (TS) is a common genetic disorder, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. A number of recent studies have allowed new insights to be gained with respect to epidemiology, genetics, cardiology, endocrinology and metabolism. Elucidation of the effects of short stature homeobox protein deficiency has explained some of the phenotypic characteristics in TS, principally short stature. Treatment with growth hormone during childhood and adolescence allows a considerable gain in adult height, although the consequences of this treatment in the very long term are not clear. Puberty must be induced in most cases, and female sex hormone replacement therapy (HRT) is given during adult years. The optimal dose of HRT has not been established and, likewise, the benefits and drawbacks of HRT have not been thoroughly evaluated. The risks of type 2 diabetes, type 1 diabetes, hypothyroidism, osteoporosis, congenital heart disease, hypertension, ischemic heart disease, aortic dilatation and dissection, inflammatory bowel disease and celiac disease are clearly elevated, and proper care during adulthood is important. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of diseases and conditions that are reviewed in the present paper. Individuals with TS need life-long medical attention.
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PMID:Clinical practice in Turner syndrome. 1692 65


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