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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fabry disease is a genetic lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system and with neuropathy as a prominent manifestation. Neurological symptoms include pain and autonomic dysfunction. This study examined peripheral autonomic nerve function in 19 female patients with Fabry disease and 19 sex and age-matched controls by measuring (1) sweat production following acetylcholine challenge; (2) the sympathetically mediated vasoconstrictor responses to inspiratory gasp, stress, and the cold pressor test; and (3) cutaneous blood flow following capsaicin. The vasoconstrictor response to inspiratory gasp was increased in Fabry patients compared to controls (p = 0.03), while the response to cold and mental stress did not change. Female patients with Fabry disease had a reduced sweat response to iontophoresis of acetylcholine (p = 0.04) and a smaller capsaicin-induced flare compared to controls. These findings suggest that female patients both have an impaired C-fiber function and local abnormalities in blood vessels and sweat glands.
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PMID:Autonomic skin responses in females with Fabry disease. 1990 79

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.
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PMID:Social-adaptive and psychological functioning of patients affected by Fabry disease. 2008 63

Fabry disease is an X-linked recessive glycolipid storage disease. It is caused by deficiency of the lysosomal enzyme alpha-galactosidase A and leads to the accumulation of the enzyme substrate, globotriasylceramide (Gb3) in many tissues including endothelial cells, pericytes and smooth muscle cells of blood vessels, renal epithelial cells, cardiac myocytes and numerous neuronal cells. In this report, we present 20-year-old male patient with ischemic stroke in pons. The case had previously been misdiagnosed as polimyositis and vasculitis. Angiokeratomas, neuropathic pain and ischemic stroke in young age suggested a Fabry disease. The diagnosis was confirmed biochemically and genetically. All young adults with stroke, especially if they have additional symptoms like angiokeratomas, proteinuria, neuropathic pain in toes and fingers should be tested for Fabry disease.
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PMID:Neurological manifestation of Fabry disease--a case report. 2012 Apr 9

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.
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PMID:Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations. 2034 50

Fabry disease (FD) is an X-linked lysosomal disorder caused by the deficient activity of the enzyme alpha-galactosidase A, which leads to multisystemic storage of globotriaosylceramide in visceral tissues and vascular endothelium. FD manifests primarily in affected hemizygous men, with a wide range of clinical signs in heterozygous women. Acroparesthesias, angiokeratomas, pain crisis, and cornea verticillata are early manifestations of FD. With age, severe complications involving the kidneys, heart, and brain cause considerable morbidity and premature death. Although the clinical onset of FD occurs in childhood, diagnosis is often delayed or missed. In men, the diagnosis must be confirmed biochemically by demonstration of decreased levels of alpha-galactosidase A activity. In women, the disease is diagnosed by identification of a mutation in the alpha-galactosidase A gene. Until a few years ago, the existing treatment for FD was based on clinical manifestations, but the advent of enzyme replacement therapy should stimulate the identification of the signs and symptoms suggestive of this disorder to allow earlier diagnosis and treatment.
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PMID:Fabry disease. 2167 97

Fabry disease (FD) is an X-linked inherited disease due to alpha-galactosidase A (alpha-Gal A) deficiency and characterized by lysosomal storage of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Storage of these substrates results in multisystem manifestations, including renal failure, cardiomyopathy, premature myocardial infarctions, stroke, chronic neuronopathic pain, gastrointestinal disturbances, and skin angiokeratoma. Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (rh-alpha-Gal A) is now available for the treatment of FD and in most patients results in clinical improvement or stabilization. However, ERT efficacy may vary in different tissues and its long-term effects remain to be defined. As a strategy to improve the efficacy of ERT, we tested the combination of rh-alpha-Gal A with the chaperone molecule 1-deoxynojirimycin (DGJ) in cultured FD fibroblasts with negligible residual enzyme activity. Compared to the effects of rh-alpha-Gal A alone, co-administration of DGJ and rh-alpha-Gal A resulted in better correction (4.8 to 16.9-fold) of intracellular alpha-Gal A activity, and increased amounts of the enzyme within the lysosomal compartment. The clearance of lyso-Gb3, one of the substrates stored in FD and a potent inhibitor of alpha-Gal A, was also significantly improved with the co-administration of DGJ and rh-alpha-Gal A. This study provides additional evidence for a synergistic effect between ERT and pharmacological chaperone therapy and supports the idea that the efficacy of combination protocols may be superior to ERT alone.
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PMID:Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and the human recombinant alpha-galactosidase A in cultured fibroblasts from patients with Fabry disease. 2397 50

Fabry disease is an X-linked inherited condition with the absence or reduction of alpha-galactosidase A- activity in lysosomes leading to accumulation of globotriaosylceramide and related neutral glycosphingolipids. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, gastrointestinal symptoms, cerebral infarction and skin and pulmonary symptoms. First symptoms of Fabry disease usually appear in childhood. The symptoms in females may be as severe as in males. Early diagnosis of Fabry disease is important because enzyme replacement therapy can stabilize the condition and prevent progression of the disease.
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PMID:[Fabry disease]. 2261 23

Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal enzyme alpha-galactosidase A, causing insufficient breakdown of glycolipids, which are stored in the eyes, kidneys, autonomic nervous system, skin, vessels and cardiovascular system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Females may be severely affected as males and both may die prematurely due to stroke, heart disease and renal failure. Enzyme replacement therapy can stabilize or reduce the progression of the disease. There is a need to improve the knowledge of Fabry disease, as an early therapy may prevent complications of the disease. This brief overview aims to raise awareness of the signs and symptoms of Fabry disease and to summarize the effects of treatments.
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PMID:Fabry disease: raising awareness of the disease among physicians. 2307 62

Fabry disease (FD) is an X-linked inborn error of metabolism caused by alpha-galactosidase A deficiency. The Fabry Registry is an ongoing observational database that compiles clinical data on patients with FD. We analyzed the Fabry Registry data of patients enrolled in Brazil to characterize the demographic and baseline clinical characteristics of this patient population. As of October 2010, 126 Brazilian patients were enrolled in the Registry (61 males, 65 females). The median age at onset of symptoms in males was 9.8 years, compared to 11.4 years in females. Males were diagnosed at a median age of 31.9 years and females at 27.1 years. The median time between the onset of first symptoms and diagnosis was 20.3 years in males and 14.3 years in females. Neurologic pain was the presenting symptom most frequently reported by both genders. Renal events were the most common clinical events reported in males, while cardiac events were the most common events in females. The results of these analyses indicate that Brazilian patients were frequently not diagnosed with FD until many years after the onset of symptoms. Many Brazilian Fabry Registry patients report experiencing neurological pain, and many Brazilian women with FD exhibit substantial signs and symptoms. The prevalence of neurological pain as a presenting symptom among Brazilian Registry patients is consistent with previous reports from the overall Registry population. FD is treatable, and earlier diagnosis will allow for prompt initiation of appropriate treatment that may avert irreversible damage that could occur during the time from symptom onset to diagnosis.
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PMID:Demographic characterization of Brazilian patients enrolled in the Fabry Registry. 2340 99

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the alpha-galactosidase A (alpha-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.
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PMID:Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease. 2455 76


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