1/42. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy.Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder for which the gene (AIRE) has recently been identified on chromosome 21q22.3. We present the mutational analyses of a French-Canadian family with APECED, in which there are two affected siblings, as well as the response to cyclosporine A(CyA) therapy in the index patient, the eldest sibling. Haplotype analysis suggested compound heterozygozity at the AIRE locus. Direct sequencing of exon 8 revealed a previously described mutation, a 13-bp deletion (1085-1097) of maternal origin, found in the index patient, her affected sister, and her unaffected sister. A novel missense mutation characterized by a T-->G transversion at nucleotide position 398, resulting in a leu-->arg amino acid substitution (L93R), was found in exon 2. The mutation was present in the father, the brother, the index patient, and the affected sister. The presence of the mutation in the propositus was verified by cloning of PCR products from genomic dna. The mutation destroys a PstI restriction enzyme site, as confirmed in the aforementioned patients. Screening of 50 French-Canadian controls with PstI digestion did not show destruction of the restriction-enzyme site. The index patient's phenotype was severe, manifested by classic features of the illness (adrenal insufficiency, hypoparathyroidism, candidiasis, and keratoconjunctivitis with alopecia universalis), as well as by severe exocrine pancreatic insufficiency, diabetes mellitus, hepatic inflammation, growth hormone (GH) deficiency due to lymphocytic hypophysitis, and primary ovarian failure. Oral CyA (5 mg/kg/day) was initiated at 13 yr of age. After 8 months of therapy, stimulated pancreatic lipase increased 24-fold with normalization of stool fat (from 31.5 g/day to 2.5 g/day, normal(N) < 5). There was complete resolution of her photophobia, and considerable hair regrowth was diffusely apparent. Minimal side effects were noted. Our experience supports the use of oral CyA for the treatment of severe APECED-associated exocrine pancreatic failure and keratoconjunctivitis.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
2/42. Case study: missed diagnosis and mistreatment of unrecognized comorbid graves disease.Comorbid medical conditions are known to complicate the course and treatment of psychiatric disorders. This case study provides the first published report of graves disease exacerbating the symptoms of Tourette's disorder and attention-deficit hyperactivity disorder (ADHD). The lack of diagnosis of the graves disease compromised the efficacy of the treatment of Tourette's disorder and ADHD. This case study supports the need to the consider increased risk of a second immunoendocrinological disorder in the presence of diabetes mellitus type I, one of the several disorders that comprise the syndrome of polyglandular autoimmune endocrinopathy type II.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
3/42. Primary biliary cirrhosis and type II autoimmune polyglandular syndrome.A 45-year-old female was diagnosed with Hashimoto's thyroiditis in 1976 and Addison's disease in 1979. At that time, her antimitochondrial antibody (AMA) level was elevated at 1:32. She subsequently developed premature ovarian failure and type I diabetes mellitus. In 1996, she became jaundiced with a cholestatic enzyme pattern. AMA was positive at a titre of 1:256. A liver biopsy confirmed the diagnosis of primary biliary cirrhosis (PBC). She underwent a liver transplantation in January 1998. This is the first report of PBC in association with type II autoimmune polyglandular syndrome. The association of PBC with other organ-specific autoimmune diseases supports an immune-mediated pathogenesis and may have implications in further studies of PBC.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
4/42. 32-year old patient presenting with autoimmune polyglandular syndrome.A 32-year-old student reported fatigue and malaise since two months in the absence of specific symptoms. Clinical examination and extensive laboratory testing revealed no abnormalities at his first presentation. Some weeks thereafter, on re-admission, hyperpigmentation suggestive of Addison's disease was observed and pathognomonic autoantibodies directed against the thyroid gland and the adrenal cortex were detected. Further evaluation led to the diagnosis autoimmune polyglandular deficiency syndrome, also named "Schmidt syndrome", comprising adrenocortical insufficiency (Addison's disease) and lymphocytic thyroiditis (Hashimoto thyroiditis). The diagnosis of polyglandular insufficiency is often delayed due to non-specific symptoms at early disease stages and progression may be rapid, culminating in Addisonian crisis under physical stress or infection, requiring immediate high-dose hormone replacement therapy. Hence, careful re-examination is mandatory to ensure adequate treatment before life-threatening complications occur. Nowadays this type of disease is classified as autoimmune polyglandular syndrome type II (APS type II) with an increased risk of developing insulin-dependent diabetes mellitus (IDDM), vitiligo, alopecia, pernicious anaemia, coeliac disease, myasthenia gravis and primary hypogonadism. The cause of the disease remains obscure but in addition to an autosomal dominant trait with variable penetrance some hints at viral infection triggering the disease process exist.- - - - - - - - - - ranking = 1.1637048783931keywords = diabetes mellitus, insulin-dependent, diabetes, mellitus (Clic here for more details about this article) |
5/42. Coexistence of common variable immunodeficiency and autoimmune polyglandular syndrome type 2.A six year-old boy with common variable immunodeficiency developed insulin dependent diabetes mellitus, autoimmune thyroiditis, and total alopecia leading to the diagnosis of autoimmune polyglandular syndrome type 2. Previously unreported co-occurence of these two entities may be explained by strong autoimmunity and HLA association of both conditions.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
6/42. Polyserositis as a rare component of polyglandular autoimmune syndrome type II.Polyglandular autoimmune (PGA) syndromes (types I and II) may affect various endocrine and non-endocrine organs in the body. In the commoner PGA type II, primary adrenal insufficiency, autoimmune thyroid disease and type I diabetes mellitus are the most frequent manifestations. serositis with pericardial or pleural involvement is not a well known component of the disease. Here, we report a 21-year-old man who first presented with a pleuropericardial effusion and Graves' disease, and who then developed type I diabetes mellitus.- - - - - - - - - - ranking = 2keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
7/42. Schmidt's syndrome in a Saudi family.We present 3 patients from a Saudi family who are presented with polyglandular autoimmune syndrome type 2. They have Addison's disease with either autoimmune thyroid disease or insulin dependent diabetic mellitus. Although this syndrome is rare, the incidence among saudi arabia or the Arab population is not known.- - - - - - - - - - ranking = 0.15644886253973keywords = mellitus (Clic here for more details about this article) |
8/42. Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations.We herein report on two Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1). The brother, who expressed a characteristic phenotype of APS-1, had developed severe mucocutaneous candidiasis in early infancy and thereafter developed hypoparathyroidism and Addison's disease, along with a severe deterioration of his immunologic function. In contrast, the 44-year-old sister, who showed a noncharacteristic phenotype of APS-1, developed insulin-dependent diabetes with high anti-glutamic acid decarboxylase antibody, mild nail candidiasis, and autoimmune hepatitis with intact immunoreactivity. She had three susceptible human leukocyte antigen (HLA) loci for type 1 autoimmune diabetes. The expression of T cell receptor (TCR)V beta 5.1 increased in both patients, while the brother showed a widely suppressed expression of many TCRV beta families. Both individuals possessed compound heterozygous novel autoimmune regulator (AIRE) gene mutations (L29P and IVS9-1G > C). The same AIRE gene mutations can thus be associated with characteristic and noncharacteristic phenotypes of APS-1, and HLA may possibly influence the phenotype of APS-1.- - - - - - - - - - ranking = 0.48984128779326keywords = insulin-dependent, diabetes (Clic here for more details about this article) |
9/42. T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity.Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-gamma after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases.- - - - - - - - - - ranking = 0.16306820470006keywords = diabetes (Clic here for more details about this article) |
10/42. A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in japan.Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessive disorder that results in several autoimmune diseases due to mutations in the AIRE (autoimmune regulator) gene. A 39-year-old female patient developed chronic mucocutaneous candidiasis at 3 yrs, idiopathic hypoparathyroidism at 11 yrs, chronic hepatitis at 23 yrs, Addison's disease and diabetes mellitus type I at 27 yrs. In addition, the patient developed progressive muscular atrophy of unknown etiology at the beginning of the third decade, and is bedridden at the present time. Her grandparents, parents, brother and daughter did not develop any features of APECED, but her father died of hepatoma. Direct sequencing of the AIRE gene revealed a novel missense mutation at exon 1 (R15C), which was identified to be of maternal origin. The other mutation was not found despite repeated sequencing of the whole coding regions. The R15C mutation was not detected in patients with idiopathic hypoparathyroidism (N= 10), idiopathic Addison's disease (N = 3), and normal subjects (N = 55). Although we could not analyze the father's gene, these results suggest that the patient is probably a compound heterozygote of the AIRE gene, in which the other abnormal allele could not be identified by the present analytical method. These data are compatible with the recent review that only one defective allele was detectable in some patients with clinically evident APECED. We found only six Japanese patients compatible with diagnosis of APECED, indicating that this autoimmune disease is extremely rare in our country.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
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