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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several hereditary disorders induce angiopathy in the intracranial cerebrovasculature and thus cause ischemic strokes. MELAS is a maternally inherited mitochondrial disorder that produces stroke-like events. Sickle cell disease, which is the result of a single base pair substitution, is a major cause of strokes in children. Homocystinuria, an autosomal recessive syndrome, produces premature atherosclerosis. Hereditary cerebroretinal vasculopathy is an autosomal dominant disorder that causes retinal and brain infarctions. Fabry disease is an x-linked disorder that can cause stroke in adults. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is an autosomal dominant syndrome that is associated with ischemic stroke and migraine-like headaches. The clinical presentation, stroke pathophysiology, and gene defects associated with these heritable disorders are reviewed.
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PMID:Mendelian and mitochondrial disorders associated with stroke. 1790 83

Since the foundations laid by Sacco and Mohr in 1989, from the Stroke data bank, cryptogenic infarctions have had a predominant place among the causes of ischemic strokes. In that study, they accounted for approximately 40% of the stroke causes. Cryptogenic infarctions are infarctions without a defined cause, despite a complete work-up; they differ from infarctions of undetermined causes, which may involve overlapping causes or an incomplete investigation. The size of this group will probably shrink as knowledge advances. Patent foramen ovale (PFO), with or without a septal aneurysm, is more frequent in patients with a cryptogenic infarction. Transesophageal echocardiography is the reference examination for screening for these abnormalities. A meta-analysis of several case-control studies showed a significant association between PFO and stroke in subjects younger than 55 years. For now, these septal abnormalities constitute a risk factor but not a cause. Complex aortic atheroma affecting area upstream of the left subclavian artery may be a source of cerebral embolisms in some conditions. The prevalence of this disease increases with age. It is identified most frequently in patients older than 60 years with a cryptogenic infarction. The thickness of the atheromatous plaque determines whether it is a risk factor or a cause. Recent stroke classifications do not consider carotid atheromatous lesions less than 50% to be a source of ischemic stroke. Nonetheless some studies identify moderate stenosis of the carotid artery more frequently in infarctions of unknown causes than in other categories. The increased risk of cerebral infarction when parents and homozygous twins have a history of stroke suggests that there may be genetic causes that have not yet been detected. An unknown genetic cause would thus be included in the infarctions of unknown causes. A recent study tested for Fabry disease in young patients with a cryptogenic infarction: 4.9% of the men and 2.4% of the women had a functional mutation of the alpha-galactosidase gene. These findings must be confirmed. Some studies suggest an association between cryptogenic infarction and hereditary thrombophilias. Nonetheless the risk attributable to these thrombophilic disorders is slight and the discovery may be only a coincidence. The work described above shows the importance of stratification in the identification of stroke causes: age older or younger than 55/60 years, type of interatrial abnormality (PFO and aneurysms of the interatrial septum), type of atheroma of the aortic arch (more or less than 4mm). They also show the difficulty involved in attributing cause to an identified abnormality: is carotid stenosis of less than 50% a marker of atherosclerosis or also a cause of stroke? To continue improving our understanding of the mechanisms of strokes, new investigational techniques are under evaluation. They include magnetic resonance imaging (MRI), computed tomographic angiography (CT), positron emission tomography (PET) of carotid plaque and of the aortic arch, transcranial Doppler, cardiac recording by telemetry, and even new biological assays.
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PMID:[Cryptogenic cerebral infarction: from classification to concept]. 1939 32

Fabry disease is an X-linked lysosomal storage disorder due to deficiency of the enzyme alpha-galactosidase A. The principal clinical manifestations of Fabry disease consist of cardiovascular complications including cerebrovascular, renal and cardiac disease but the pathophysiology of this specific vasculopathy is unclear. With the development of targeted treatment for Fabry disease, i.e. enzyme replacement therapy, it has become apparent that the removal of stored glycosphingolipid from the endothelial cells does not prevent progression of vascular disease in many patients. The aim of this study is to review the current available literature on vascular function tests, imaging and pathology studies and propose a hypothesis on the evolution of arterial complications in Fabry disease. Clearly, although premature atherosclerosis is suggested to occur, most studies describe absence of characteristic plaque formation. Smooth muscle cell hypertrophy, is probably the earliest feature of a complex vasculopathy, as in females and atypical cardiac variants, who have residual enzyme activity, no endothelial storage of significance is found. Subsequently, processes occur as observed in neo intima formation however with formation of more fibrotic structures. In the presence of a hyperdynamic circulation in combination with a less compliant vascular wall, it is hypothesized that upregulation of local renin angiotensine systems may occur. Angiotensin II is known to increase adhesion molecules, cytokines and chemokines and exerts a pro-inflammatory effect on leucocytes, endothelial cells and vascular smooth muscle cells. This enhances release of pro-thrombotic factors and opposes actions mediated through angiotensin 2 (AT2) receptor, including the release of nitric oxide (NO). A combination of reduced vascular compliance and activation of pro-thrombotic factors can lead to vascular complications in Fabry disease.
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PMID:Vasculopathy in patients with Fabry disease: current controversies and research directions. 1990 Aug 28

White matter lesions (WMLs), commonly seen as hyperintensities on T2-weighted MRI scans of healthy elderly individuals, are considered to be related to small vessel disease in the brain, and are often associated with subtle cognitive and functional impairments. WMLs also show a strong correlation with a wide range of neurodegenerative and neuropsychiatric disorders. Although a number of vascular risk factors for WMLs have been identified, genetic factors are also important with twin and family studies reporting high heritability. Mutations in several genes have been described that lead to monogenic disorders manifesting WMLs, such as Fabry disease and CADASIL. Because most individuals with WMLs do not have Mendelian disorders, most of the focus has been on single nucleotide polymorphisms as genetic risk markers for WMLs, either directly or through their interactions with other genes or medical risk factors. Candidate genes examined to date include those involved in cholesterol regulation and atherosclerosis, hypertension, neuronal repair, homocysteine levels, and oxidative stress pathways. In addition, although there have been a few genome-wide linkage studies, only one genome-wide association study has been performed. The majority of the genetic findings need independent replication, and studies need to be extended to other candidate genes. Collaborative efforts to examine genome-wide associations in large samples of both sexes of a broad age range using longitudinal studies are necessary. The identification of individuals genetically at risk of developing white matter lesions will have important implications for recognizing the etiology of WMLs and thereby developing clinical intervention strategies for their prevention.
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PMID:The genetics of white matter lesions. 2195 72

In 1882, Philippe Gaucher described a 32-year-old woman with massive splenomegaly and unusually large cells in the spleen, which he called a "primary epithelioma of the spleen." The systemic nature and inheritance of the disease and its variants involving the viscera and CNS were described over the next century. The delineation of the causal enzymatic defects, genetics, molecular pathology, and genomics have provided pathogenic insights into the phenotypic spectrum and the bases for development of specific therapies for what is now known as Gaucher disease. As a prototype, the clinically and economically successful intracellular enzyme therapy provided the impetus for the expansion of similar research and therapeutic developments for other lysosomal storage diseases (LSDs) and orphan diseases, including Fabry, Pompe, and Niemann-Pick diseases, as well as several mucopolysaccharidoses. Continuing studies of such LSDs, which occur as a group in more than 7000 live births, have revealed the complex molecular interdigitation with the autophagy and apoptotic pathways and proteostasis and the impact of disruptions of the lysosomal/autophagy and proteostasis systems on more common diseases has been recognized. Examples include age-related neurodegenerative diseases (eg, Parkinson disease and Gaucher disease), idiopathic hypertrophic myocardiopathies, stroke and renal failure (eg, Fabry disease), and Nonalcoholic Fatty Liver Disease/Nonalcoholic SteatoHepatitis (NAFLD/NASH) and atherosclerosis (eg, lysosomal acid lipase deficiencies). Although perceived as rare, the availability of treatment and the impact of the LSDs on more common diseases require their integration into routine clinical practice.
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PMID:Gaucher disease and other storage disorders. 2323 55


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