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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and approximately 5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level.
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PMID:Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion. 865 Dec 80

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.
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PMID:[Congenital diabetes insipidus. Recent advances in molecular genetics]. 868 70

The majority of cases of central diabetes insipidus are still pathogenetically unclear (idiopathic). Atherosclerotic cholesterol emboli might be partly responsible for some of these idiopathic cases. A 54-year-old woman with known aortic valve stenosis and a history of a transitory ischemic attack presented with sudden-onset polyuria and polydipsia of up to eight l/d, which had started acutely with headaches. She had been treated with lithium for 3 years because of cyclothymic depression. Plasma sodium was in the upper normal range (142-148 mmol/l). Hypertonic saline infusion during lithium therapy revealed a normal threshold of thirst and resetting of vasopressin secretion (osmotic threshold > 300 mosmol/l), whereas vasopressin reserve was normal. Lithium withdrawal led to an even greater delay of vasopressin release upon hypertonic saline infusion (> 310 mosmol/l). Pituitary function tests revealed a normal anterior pituitary function. MR imaging of the hypothalamo-hypophyseal region showed a normal hypothalamic region and a highly intensive neurohypophyseal signal in the T1-weighted image. The patient responded well to desmopressin. We suggest that in this rare case clinical symptoms as well as biochemical findings like impairment of AVP release might be related to a minor structural hypothalamic damage by a vascular lesion, caused, for example, by an atheromatous (cholesterol) embolism in the hypothalamic region responsible for integration of osmoreceptor function and AVP-secretion. The patient's atherosclerosis and aortic stenosis might be responsible for this event.
Exp Clin Endocrinol Diabetes 1997
PMID:Atherosclerosis, aortic stenosis and sudden onset central diabetes insipidus. 928 11

Wolfram or DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, which has long been known as an autosomal-recessive disorder, has recently been proposed to be a mitochondrial-mediated disease with either a nuclear or a mitochondrial genetic background. The phenotypic characteristics of the syndrome resemble those found in other mitochondrial (mt)DNA mediated disorders such as Leber's hereditary optic neuropathy (LHON) or maternally inherited diabetes and deafness (MIDD). Therefore, we looked for respective mtDNA alterations in blood samples from 7 patients with DIDMOAD syndrome using SSCP-analysis of PCR-amplified fragments, encompassing all mitochondrial ND and tRNA genes, followed by direct sequencing. Subsequently, we compared mtDNA variants identified in this disease group with those detected in a group of LHON patients (n = 17) and in a group of 69 healthy controls. We found that 4/7 (57%) DIDMOAD patients harbored a specific set of point mutations in tRNA and ND genes including the so-called class II or secondary LHON mutations at nucleotide positions (nps) 4216 and 4917 (haplogroup B). In contrast, LHON-patients were frequently (10/17, 59%) found in association with another cluster of mtDNA variants including the secondary LHON mutations at nps 4216 and 13708 and further mtDNA polymorphisms in ND genes (haplogroup A), overlapping with haplogroup B only by variants at nps 4216 and 11251. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. We propose that haplogroup B represents a susceptibility factor for DIDMOAD which, by interaction with further exogeneous or genetic factors, might increase the risk for disease.
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PMID:Analysis of the mitochondrial DNA from patients with Wolfram (DIDMOAD) syndrome. 930 89

Wolfram syndrome (MIM 222300) is the association of juvenile onset diabetes mellitus and optic atrophy, also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients present with diabetes mellitus followed by optic atrophy in the first decade, cranial diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade. Other abnormalities include primary gonadal atrophy. Death occurs prematurely, often from respiratory failure associated with brainstem atrophy. Most patients eventually develop all complications of this progressive, neurodegenerative disorder. The pathogenesis is unknown, but the prevalence is 1 in 770000 in the UK and inheritance is autosomal recessive. A Wolfram gene has recently been mapped to chromosome 4p16.1, but there is evidence for locus heterogeneity, and it is still possible that a minority of patients may harbour a mitochondrial genome deletion. The best available diagnostic criteria are juvenile onset diabetes mellitus and optic atrophy, but there is a wide differential diagnosis which includes other causes of neurodegeneration.
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PMID:Wolfram (DIDMOAD) syndrome. 935 Aug 17

Tumors in the suprasellar region may cause both visual and endocrinologic symptoms. This association, well known to modern physicians, was established during the 19th century. However, we have identified a 16th-century autopsy report, written by the Dutch professor of anatomy Pieter Pauw (1564-1617), which describes an 18-year-old girl who developed marked polyuria and subsequently became totally blind from a cystic tumor compressing the optic chiasm. Based on prevailing theories on the nature of diabetes, Pauw attributed the disease to the kidneys. Undoubtedly, however, his lucid report is the earliest known account of diabetes insipidus caused by an arachnoid cyst, the Rathke cleft cyst, or craniopharyngioma in the region of the pouch of Rathke. The description also gives insights into the role of anatomic dissections in late 16th-century northern Europe.
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PMID:Diabetes insipidus and blindness caused by a suprasellar tumor: Pieter Pauw's observations from the 16th century. 955 52

We describe a Thai family with three children, two of whom presented with Wolfram syndrome, which is a rare syndrome characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness and urinary tract dilatation. A girl and her younger brother had insulin-dependent diabetes mellitus at 11 years old with early onset of renal impairment, proteinuria and hypertension. Urinary tract dilatation was demonstrated in both patients. Kidney biopsies were compatible with diabetic nephropathy. Both children also had bilateral sensorineural hearing loss. Optic atrophy with severe loss of vision was detected in the girl and bilateral cataract in her brother. Both patients were HLA DR2 positive. At 16 years old, her creatinine clearance was 16 ml/min/1.73 m2. Her brother's creatinine clearance was 25 ml/min/1.73 m2 at 13 years old. We conclude that renal function should be evaluated in patients with Wolfram syndrome and the cause of renal failure in these patients may be rapid and severe diabetic nephropathy.
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PMID:Renal failure in two patients with Wolfram syndrome. 946 37

Wolfram syndrome is the association of diabetes mellitus and optic atrophy, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Incomplete characterisation has caused diagnostic confusion; we therefore undertook a nation-wide cross-sectional case finding study. We identified 45 patients with Wolfram syndrome, median age 29 years. All patients fulfilled the ascertainment criteria (juvenile onset diabetes mellitus and optic atrophy). Optic atrophy presented in 38 patients with reduced visual acuity and colour vision defect (median age 11 years), progressing to visual acuity of 6/60 or less in 35 patients (median time 8 years, range 1-25 years). Visual field examinations recorded before acuity deteriorated showed central scotomas with peripheral constriction. Blind patients had absent pupillary reflexes. Horizontal nystagmus was seen in patients with other signs of cerebellar degeneration. There was no pigmentary retinal dystrophy; only 3 patients had background diabetic retinopathy, despite a median duration of diabetes of 24 years. Electroretinography was normal in 3 patients and showed reduced amplitude in 3 patients; visual evoked responses were abnormal (10/10 patients: reduced amplitude to both flash and pattern stimulation). Magnetic resonance imaging showed generalised brain atrophy with reduced signal from the optic nerves and chiasm. A postmortem brain specimen from one patient revealed atrophy of the optic nerves, chiasm, cerebellum and brainstem. We found no evidence of mitochondrial genome defects or rearrangements. This primary neurogenerative disorder presents with diabetes mellitus and progressive optic atrophy, probably due to pathology in the optic nerve.
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PMID:Optic atrophy in Wolfram (DIDMOAD) syndrome. 953 52

We report a sporadic case of Albright's hereditary osteodystrophy (AHO)-like syndrome with several endocrinopathies. A 37-yr-old woman had an appearance of AHO but did not have renal PTH resistance. Her case was complicated by non-insulin-dependent diabetes mellitus with severe insulin resistance, central diabetes insipidus, and hyposecretion of GH. Most patients with AHO are found in a family of pseudohypoparathyroidism type-Ia and have a heterozygous mutation that inactivates the alpha-subunit of Gs (Gs alpha), the stimulatory regulator of adenylyl cyclase. Some sporadic cases occur in which patients with phenotype similar to AHO have a deletion of chromosome 2q37. However, in this patient, both the Gs alpha gene structure and the biological activity were normal. In addition, chromosome analysis revealed a normal pattern with no visible deletion of chromosome 2q37. Our findings suggest that one or more other factors may be involved in the pathogenesis of AHO-related disease.
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PMID:A case of Albright's hereditary osteodystrophy-like syndrome complicated by several endocrinopathies: normal Gs alpha gene and chromosome 2q37. 958 56

A case is described of acute leukosis presenting with unusual clinical picture. In a female patient aged forty nine presenting with signs of diabetes insipidus, blood count revealed thrombocytosis together with alterations suggesting acute leukosis. Bone marrow blasts showed the typical morphological features of megakaryoblasts. Institution of chemotherapy made for dispelling of diabetes-insipidus manifestations. To the authors' thinking, they observed a rare megakaryoblastic variety of acute leukosis caused by leukotic infiltration of the hypothalamohypophyseal zone in a patient wasted by heavy urination as is common in diabetes insipidus.
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PMID:[A case of acute leukemia with a diabetes insipidus syndrome and thrombocytosis]. 967 Jun 92


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