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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the etiology of Hirschsprung's disease and neuronal intestinal dysplasia remains obscure, both have histological abnormalities involving ganglion cells and neuronal elements. Searching for a common pathway that may inhibit normal maturation of neurogenic precursors, we examined the possible role of an immune mechanism in the maldevelopment of the enteric neural network. Six patients with Hirschsprung's disease were studied by comparing biopsy specimens from diseased colon with ones taken from proximal ganglionic colon in the same patients. These were similarly compared with colonic biopsy specimens from patients studied with chronic constipation or bowel removed at the time of operation for other disorders. Biopsies were taken from four other patients with neuronal intestinal dysplasia. Each was examined by hematoxylin & eosin staining, acetylcholinesterase histochemistry, and immunohistochemistry of major histocompatibility complex (MHC) class I and class II antigens. All rectal samples from Hirschsprung's disease patients exhibited elevated acetylcholinesterase histochemistry and absent ganglia to confirm the diagnosis. These findings were correlated with marked elevation of class II MHC in the aganglionic area, whereas the proximal normal ganglionic segments showed no elevation. Rectal biopsy specimens from patients with chronic constipation exhibited no such elevation. A similar elevation of class II MHC was detected in the mucosa and submucosa of all four patients with the rare neuronal intestinal dysplasia disorder whose diagnosis was confirmed by giant ganglia in Auerbach's plexuses, aberrant Meissner's ganglia in the lamina propria mucosa, and giant neurofibrils in the mucosa and submucosa. The correlation of elevated class II MHC in these two neuronal dysfunction disorders may indicate an underlying autoimmune mechanism as is seen in thyroiditis and insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ectopic class II major histocompatibility antigens in Hirschsprung's disease and neuronal intestinal dysplasia. 150 Oct 11

A. PATIENT SURVIVAL 1. The best cadaver graft patient survival 3-years posttransplant was observed in those whose primary disease was either nephrotic syndrome (98%), renal hypoplasia (98%), renal dysplasia (98%), IgA nephropathy (96%), or medullary cystic disease (97%). The worst survival was in those with Goodpasture's syndrome (88%), hypertensive nephrosclerosis (87%), MPGN (87%), IDDM (86%), and NIDDM (85%). 2. Patient survival correlated inversely with nonimmunologic graft loss. Nonimmunologic graft loss was high in patients with hypertensive nephrosclerosis (21%), polycystic kidney disease (23%), IDDM (27%), and NIDDM (27%). 3. Females with CGN and IDDM had better patient survival than males with the same diseases. The 2-, 3-, and 5-year survivals for females with IDDM were 91%, 89%, and 87% whereas for males, they were 87%, 84%, and 81%, respectively (p = 0.01). For CGN the 2-, 3-, and 5-year survivals were 95%, 94%, and 93% for females and 93%, 91%, and 90% for males (p less than 0.01). Females with Alport's syndrome had lower patient survival rates at 1 year (86%) than males (95%, p = 0.03). B. GRAFT SURVIVAL 1. The best 3-year graft survival was in recipients whose primary pathology was IgA nephropathy with 83% for cadaver grafts and 95% for LRD grafts. This was not secondary to center effects. The worst graft survival at 3 years for cadaver kidney recipients was in those whose primary illness was NIDDM (61%), hypertensive nephrosclerosis (58%), MPGN (59%), and Goodpasture's syndrome (59%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of kidney transplantation in different diseases. 210 68

Two sibs with early onset diabetes and epiphysed dysplasia (Wolcott-Rallison syndrome) are described. The epiphyseal changes were radiologically apparent at 6 months of age in one of them, and both developed insulin dependent diabetes in the first few weeks of life. The clinical and radiological features of this syndrome are reviewed.
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PMID:Wolcott-Rallison syndrome. 755 Nov 59

Several malformations and malformation complexes have been alleged to be associated with maternal type 1 diabetes mellitus: in particular, sacral dysplasia, caudal regression/sirenomelia, femoral dysplasia, and holoprosencephaly. For some of the malformations the claim rests on case material, and for others on theoretical considerations. The history and evolution of these ideas are presented.
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PMID:Case reports of malformations associated with maternal diabetes: history and critique. 833 Apr 51

Wolcott-Rallison syndrome (WRS) is an autosomal recessive disorder characterized by neonatal or early infancy type 1 diabetes, epiphyseal dysplasia, and growth retardation. Mutations in the EIF2AK3 gene, encoding the eukaryotic initiation factor 2alpha-kinase 3 (EIF2AK3), have been found in WRS patients. Here we describe a girl who came to our attention at 2 months of age with severe hypertonic dehydration and diabetic ketoacidosis. A diagnosis of type 1 diabetes was made and insulin treatment initiated. Growth retardation and microcephaly were also present. Anti-islet cell autoantibodies were negative, and mitochondrial diabetes was excluded. Imaging revealed a hypoplastic pancreas and typical signs of spondylo-epiphyseal dysplasia. The diagnosis of WRS was therefore made at age 5 years. Sequencing analysis of her EIF2AK3 gene revealed the presence of a homozygous T to C exchange in exon 13 leading to the missense serine 877 proline mutation. The mutated kinase, although it partly retains the ability of autophosphorylation, is unable to phosphorylate its natural substrate, eukaryotic initiation factor 2alpha (eIF2alpha). This is the first case in which the pathophysiological role of EIF2AK3 deficiency in WRS is confirmed at the molecular level. Our data demonstrate that EIF2AK3 kinase activity is essential for pancreas islet function and bone development in humans, and we suggest EIF2AK3 as a possible target for therapeutic intervention in diabetes.
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PMID:Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. 1208 64

TCF2, the gene encoding for hepatocyte nuclear factor 1beta, is involved in early renal development. Mutations in TCF2 lead to heterogeneous renal phenotypes. Antenatal ultrasonography may show unilateral/bilateral hyperechogenic or enlarged cystic kidneys. In children or adults, cystic renal hypoplasia/dysplasia is a common feature, occasionally associated with maturity-onset diabetes of the young type 5 and genital tract abnormalities. We report an unusual presentation characterized by massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in monozygotic twins. Bilateral enlarged cystic kidneys were discovered in week 13 of a gemellic pregnancy. Postnatally, kidney size increased in both children, reaching 16 cm at 20 years. Nephromegaly was associated with bilateral cysts and a slowly decreasing glomerular filtration rate (40 mL/min/1.73 m(2) at 20 years). There was neither pancreatic nor genital malformation. Non-type 1 diabetes mellitus was diagnosed incidentally in both twins at 20 years. Knowledge of early-onset diabetes (at age 19 years) in their father prompted us to search for the TCF2 mutation. Genetic analysis showed complete TCF2 heterozygous whole-gene deletion in both twins. Genetic testing could not be performed in the father. Bilateral massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in young adults may be related to TCF2 mutation. Although uncommon, this new phenotype enlarges the clinical spectrum of kidney involvement associated with TCF2 mutation. In this case, maturity-onset diabetes of the young-type diabetes paved the way to accurate diagnosis.
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PMID:Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1beta (hepatocyte nuclear factor-1beta) heterozygous whole-gene deletion. 1803 3

The study included 68 patients aged 18-32 years with newly diagnosed type 1 diabetes (DM) and/or undifferentiated connective tissue dysplasia (CTD). Ten healthy subjects without clinical symptoms of CTD served as controls. Induced platelet aggregation, Willebrand factor activity, plasma thromboxane B2, 6-keto-prostaglandin F1a, and endotheline-1 were measured. The results suggest relatively normal functional reserves of endothelium and platelet activity in patients with newly diagnosed DM and compensated carbohydrate metabolism. Elevated vasopressor activity and platelet aggregation in patients with DM and CTD compared with patients without CTD may be one of the mechanisms of angiopathy.
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PMID:[Endothelium condition and platelet aggregation in patients with newly diagnosed type 1 diabetes mellitus and undifferentiated connective tissue dysplasia]. 1956 29

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype.
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PMID:Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. 2020 48

Shwachman-Diamond syndrome is a rare clinical condition consisting of exocrine pancreatic dysfunction, various degree of pancytopenia, and metaphyseal dysplasia. The majority of Shwachman-Diamond syndrome cases result from mutations in the Shwachman-Bodian-Diamond Syndrome gene. To date, type 1 diabetes mellitus has only been reported in 4 independent cases presenting with Shwachman-Diamond syndrome, 3 of them with molecular confirmation of the diagnosis. We describe 2 unrelated patients with clinical and molecular features typical of Shwachman-Diamond syndrome and type 1 diabetes mellitus. In addition, we report the occurrence rate of type 1 diabetes mellitus in the Italian registry for Shwachman-Diamond syndrome, which is low (3.23%) but increased at least 30-fold over the type 1 diabetes mellitus occurrence rate in the general population. No evidence of a direct correlation between Shwachman-Diamond syndrome and type 1 diabetes mellitus have been reported, therefore the presence of both diseases in the same patient might be a chance association, however we suggest that the defects in immune regulation of Shwachman-Diamond syndrome might play a role in the development of type 1 diabetes mellitus.
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PMID:Shwachman-Diamond syndrome and type 1 diabetes mellitus: more than a chance association? 2155 66

McCune-Albright syndrome (MAS) consists of the triad of polyostotic fibrous dysplasia, cutaneous pigmentation, and multiple endocrine abnormalities. Type 1 diabetes mellitus is not included in MAS. We report the case of an 18-year-old girl who presented with McCune-Albright syndrome. The diagnosis was made by the presence of precocious puberty at the age of 6 years, cutaneous pigmentation, polyostotic fibrous dysplasia, and phosphate diabetes. Type 1 diabetes mellitus developed at the age of 16 years. We discuss this case, the relationship between type 1 diabetes mellitus and MAS, with a literature review.
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PMID:[McCune-Albright syndrome associated with diabetes mellitus]. 2228 33


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