Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 56-year-old man with diabetes mellitus and alcoholic liver cirrhosis was admitted on an emergency basis to our hospital for further examination of headache, general fatigue and dysarthria. He had been treated with antifungal drugs on the suspicion of pulmonary mycosis. Brain MRI revealed multiple cerebellar abscesses with ring enhancement. Due to depression of mental status despite medical treatment, he underwent suboccipital craniotomy and enucleation of the cerebellar abscess, resulting in marked improvement of consciousness level. As the culture of his abscess content yielded Nocardia farcinica, the definite diagnosis of Nocardial cerebellar abscesses and pulmonary Nocardiosis were made. Pulmonary Nocardiosis improved by oral co-trimoxazole treatment. Moreover, no recurrence of cerebellar abscesses was evident. This case indicates that the possibility of Nocardial infection should be considered in the immuno-compromised hosts.
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PMID:[Pulmonary nocardiosis complicated with multiple cerebellar abscess]. 1919 10

Lacunar infarcts or small subcortical infarcts result from occlusion of a single penetrating artery and account for one quarter of cerebral infarctions. Patients with a lacunar infarct usually present with a classical lacunar syndrome (pure motor hemiparesis, pure sensory syndrome, sensorimotor stroke, ataxic hemiparesis or dysarthria-clumsy hand) and, less frequently, an atypical lacunar syndrome. Hypertension and diabetes mellitus are major risk factors for lacunar stroke. Lacunar infarcts show a paradoxical clinical course with a favorable prognosis in the short term, characterized by a low early mortality and reduced functional disability on hospital discharge, but with an increased risk of death, stroke recurrence and dementia in the mid- and long term. Asymptomatic progression of small-vessel disease is a typical feature of the lacunar infarcts. For this reason, lacunar infarction should be regarded as a potentially severe condition rather than a relatively benign disorder and, therefore, lacunar stroke patients require adequate and rigorous management and follow-up. Antiplatelet drugs, careful blood pressure control, the use of statins and modification of lifestyle risk factors are key elements in secondary prevention after lacunar stroke.
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PMID:Lacunar stroke. 1921 Jan 94

Friedreich ataxia is the most frequent hereditary ataxia, with an estimated prevalence of 3-4 cases per 100,000 individuals. This autosomal-recessive neurodegenerative disease is characterized by progressive gait and limb ataxia, dysarthria, lower-limb areflexia, decreased vibration sense, muscular weakness in the legs, and a positive extensor plantar response. Non-neurological signs include hypertrophic cardiomyopathy and diabetes mellitus. Symptom onset typically occurs around puberty, and life expectancy is 40-50 years. Friedreich ataxia is usually caused by a large GAA-triplet-repeat expansion within the first intron of the frataxin (FXN) gene. FXN mutations cause deficiencies of the iron-sulfur cluster-containing subunits of the mitochondrial electron transport complexes I, II, and III, and of the iron-sulfur protein aconitase. Mitochondrial dysfunction has been addressed in several open-label, non-placebo-controlled trials, which indicated that treatment with idebenone might ameliorate hypertrophic cardiomyopathy; a well-designed phase II trial suggested concentration-dependent functional improvements in non-wheelchair-bound children and adolescents. Other current experimental approaches address iron-mediated toxicity, or aim to increase FXN expression through the use of erythropoietin and histone deacetylase inhibitors. This Review provides guidelines, from a European perspective, for the diagnosis of Friedreich ataxia, differential diagnosis of ataxias and genetic counseling, and treatment of neurological and non-neurological symptoms.
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PMID:Diagnosis and treatment of Friedreich ataxia: a European perspective. 1934 27

Progressive external ophthalmoplegia (PEO) can be caused by a disorder characterized by multiple mitochondrial DNA (mtDNA) deletions due to mutations in the TWINKLE gene, encoding a mtDNA helicase. We describe a 71-year-old woman who had developed PEO at age 55 years. She had cataracts, diabetes, paresthesias, cognitive defects, memory problems, hearing loss, and sensory ataxia. She had muscle weakness with ragged red fibers on biopsy. MRI showed static white matter changes. A c.908G>A substitution (p.R303Q) in the TWINKLE gene was identified. Multiple mtDNA deletions were detected in muscle but not blood by a PCR-based method, but not by Southern blot analysis. MtDNA copy number was maintained in blood and muscle. A systematic literature search was used to identify the genotypic and phenotypic spectrum of dominant TWINKLE-related disease. Patients were adults with PEO and symptoms including myopathy, neuropathy, dysarthria or dysphagia, sensory ataxia, and parkinsonism. Diabetes, cataract, memory loss, hearing loss, and cardiac problems were infrequent. All reported mutations clustered between amino acids 303 and 508 with no mutations at the N-terminal half of the gene. The TWINKLE gene should be analyzed in adults with PEO even in the absence of mtDNA deletions in muscle on Southern blot analysis, and of a family history for PEO. The pathogenic mutations identified 5' beyond the linker region suggest a functional role for this part of the protein despite the absence of a primase function in humans. In our patient, the pathogenesis involved multiple mtDNA deletions without reduction in mtDNA copy number.
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PMID:Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease. 1935 76

Progressive signs of ataxia in a eight years old girl prompted neurological investigation. The girl had unstable gait with incoordination of limb movements, impairment of position and vibratory senses, dysarthria, pes cavus, positive Babinski sign and scoliosis. At the age of fourteen the girl was referred in a comatose condition, in a severe diabetic ketoacidosis. Ataxia and hypoactive knee and ankle jerks prompted the analysis of the frataxin gene (FXN; 606829). The most common molecular abnormality: GAA trinucleotide repeat expansion in intron 1 was found with + 300 GAA repeats (1490bp) (normal individuals have 5 to 30 GAA repeat expansions, whereas affected individuals have from 70 to more than 1,000 GAA triplets). Electrocardiogram showed diffuse T wave inversion with sinus bradycardia, while ultrasound revealed concentric, symmetric hypertrophy of left ventricle leading to the diagnosis of hyperthrophic cardiomyopathy. At the age of 14 years, the patient was bound to the wheel-chair, unable to walk. Her brother started to show ataxia at the age of 8 years, and subsequent analysis showed hyperthrophic cardiomyopathy, too. His mutational analysis revealed the same frataxin abnormality, with + 300 GAA repeats. So far, no signs of diabetes occurred. The parents are heterozygous with FXN of 9 -10 GAA (490 bp). Both children received a beta blocker, while the girl's diabetes mellitus was treated by insulin preparations. This is a report of two siblings with Fridreich ataxia and hyperthrophic cardiomyopathy. In addition, the girl developed type 1 diabetes mellitus.
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PMID:Friedreich ataxia (FA) associated with diabetes mellitus type 1 and hyperthrophic cardiomyopathy. 1948 41

It has become increasingly apparent, especially with the advent of MRI brain scanning, that a large number of patients develop signal intensity changes in the subcortical white matter and periventricular region as they age. This appears to be accelerated by risk factors for small vessel cerebrovascular disease such as hypertension, smoking, diabetes mellitus and hyperlipidemia. The major question becomes when such changes become clinically significant. It is obvious that subcortical lacunar-type infarction can be identified by the clinical presentation. For example, typical examples of so-called "lacunar syndrome" include pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, clumsy hand-dysarthria, and hemiataxia-hemiparesis. The issue becomes a measure of impact on functional ability. This is influenced by several factors. Baseline IQ and educational level, as well as expectations of age, certainly play a role. A person who develops cognitive impairment and long tract signs in their 50s or 60s is certainly going to be recognized as more impaired than an 80 year old individual who is retired and primarily is engaged in recreational activity. It would be expected that a person born with limited intellectual capacity and/or limited educational opportunity would be less likely to be identified as impaired than a person who has achieved substantial economic achievement through their innate talents. The concept of tissue loss or lesion load becomes important when determining how pronounced the ischemic cerebrovascular changes translate into functional impairment. Correlative pathology may include cortical atrophy and ventricular dilatation. Loss of either cortical or subcortical tissue function is expected to be related to functional compromise. In addition, there are potential features such as the coexistence of small vessel cerebrovascular disease and Alzheimer's disease. Small vessel cerebrovascular disease might also play a contributing factor in patients susceptible to Dementia with Lewy Bodies or patients susceptible to fronto-temporal dementia or any other dementing process. Thus, the concept of tissue loss or lesion burden of disease becomes increasingly important as we recognize the potential for multifactorial issues, including genetic factors, to contribute to the phenotypic expression. The relationships between cognitive impairment, dementia and subcortical vascular lesions are poorly understood. There have been several papers on the different aspects of cerebral insults and their impact on cognition, the various kinds of dementia and different methods of analyzing the impact of the various insults to the brain. This chapter is an attempt to review all pertinent information currently available on the poorly understood condition of "subcortical ischemic cerebrovascular dementia."
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PMID:Subcortical ischemic cerebrovascular dementia. 1950 11

Progressive signs of ataxia in a eight year old girl with hypo-active knee and ankle jerks, prompted the analysis of the frataxin gene (FXN; 606829). The most common molecular abnormality--GAA trinucleotide repeat expansion in intron 1--was found with +300 GAA repeats (1490 bp) (normal individuals have 5 to 30 GAA repeats expansions, whereas affected individuals have from 70 to more than 1000 GAA triplets). Additionally she had unstable gait with incoordination of limb movements, impairment of position and vibratory senses, dysarthria, pes cavus, positive Babinski sign and scoliosis. At the age of fourteen the girl was referred in a comatose condition, in severe diabetic ketoacidosis. Insulin dependent diabetes mellitus was since treated with insulin preparations. Electrocardiogram showed diffuse T wave inversion with sinus bradycardia, while ultrasound revealed concentric, symmetric hypertrophy of the left ventricle leading to the diagnosis of hypertrophic cardiomyopathy. At the age of 14, she is bound to the wheelchair, unable to walk. Her brother started to show ataxia at the age of 8 years and subsequent analysis also showed hypertrophic cardiomyopathy. His mutational analysis revealed the same frataxin abnormality with +300 GAA repeats. So far, no signs of diabetes occurred. The parental DNA was not available for analysis.
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PMID:Friedreich's ataxia (FA) associated with diabetes mellitus type 1 and hypertrophic cardiomyopathy: analysis of a FA family. 1953 71

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family.
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PMID:48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis. 2082 36

A 34-year-old Thai woman developed acute left hemiparesis with dysarthria from subcortical infarction of the right MCA territory eighteen months after being diagnosed with Noonan syndrome, diabetes mellitus, dyslipidaemia, and hypertension. Further investigations suggested atherosclerosis as a cause. Modifying her risk factors was difficult, partly because of limited adherence. Three years later, she had another attack of ischaemic stroke in the same area. Unlike the three previously reported cases, the causation of strokes in this patient appeared to be a more 'complex' interaction between genetic defect and environment including possible subtle arterial abnormalities, metabolic risk factors, and mental insufficiency.
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PMID:Noonan syndrome, metabolic syndrome and stroke-in-the-young: coincidence, causal or contribution? 2087 82

Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin. Additional features include hypertrophic cardiomyopathy and diabetes. Large GAA repeat expansions in the first intron of the FXN gene are the most common mutation underlying FRDA. Patients show severely reduced levels of a FXN-encoded mitochondrial protein called frataxin. Frataxin deficiency is associated with abnormalities of iron metabolism: decreased iron-sulfur cluster (ISC) biogenesis, accumulation of iron in mitochondria and depletion in the cytosol, enhanced cellular iron uptake. Some models have also shown reduced heme synthesis. Evidence for oxidative stress has been reported. Respiratory chain dysfunction aggravates oxidative stress by increasing leakage of electrons and the formation of superoxide. In vitro studies have demonstrated that Frataxin deficient cells not only generate more free radicals, but also show a reduced capacity to mobilize antioxidant defenses. The search for experimental drugs increasing the amount of frataxin is a very active and timely area of investigation. In cellular and in animal model systems, the replacement of frataxin function seems to alleviate the symptoms or even completely reverse the phenotype. Therefore, drugs increasing the amount of frataxin are attractive candidates for novel therapies. This review will discuss recent findings on FRDA pathogenesis, frataxin function, new treatments, as well as recent animal and cellular models. Controversial aspects are also discussed.
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PMID:Friedreich's ataxia: past, present and future. 2155 Jun 66


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