Gene/Protein Disease Symptom Drug Enzyme Compound
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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 rare X-linked lysosomal storage disorder caused by deficient activity of alpha-galactosidase A (alpha-Gal A) resulting in the storage of glycosphingolipids, especially globotriaosylceramide (Gb3), in cells throughout the body, causing life-threatening renal, cardiac, and cerebrovascular complications in hemizygous males and some heterozygous females. Disease manifestations in heterozygotes are being recognized increasingly, but quantitative prospective data on their extent and severity are limited. Prospective clinical and laboratory assessments were performed in a 7-day study of 61 women with signs and symptoms of Fabry disease. Analyses included medical history and physical, neurologic, cardiac, and ophthalmologic assessments; laboratory assessments; renal function tests; magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head; and Fabry-related blood and urine tests, including Gb3 levels in blood and urine, skin biopsies, and DNA genotype analysis of the alpha-Gal A gene to identify causative mutations. Quality of life, pain and concomitant medication were documented using validated questionnaires and diaries. All patients had normal Gb3 levels in plasma; only 1 patient had visible storage material in the superficial dermal vascular endothelial cells. Cardiac, renal, or cerebrovascular abnormalities were documented in 52 of the 57 patients (91%) with confirmed Fabry genotypes. These included electrocardiographic abnormalities in 38 of 52 patients (73%), echocardiographic abnormalities in 8 of 57 (14%), proteinuria (>150 g protein/24-h urine) in 23 of 38 (61%), low estimated glomerular filtration rate (<90 mL/min per 1.73 m) in 24 of 57 (42%), abnormal MRI in 4 of 54 (7%), and abnormal MRA in 10 of 50 patients (20%). Angiokeratomas and corneal epitheliopathy were documented in 63% and 82% of the 57 patients, respectively. Despite the virtual absence of storage material in plasma and skin vascular endothelial cells, this population of women with Fabry disease exhibited a wide spectrum of clinical abnormalities. Useful outcome measures for assessment of specific therapies need to be developed. Studies limited to homogeneously affected subjects may be possible.
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PMID:The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. 1614 26

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male and female patients with the same prevalence, while females with FD seem to be less severely affected. The course of untreated illness is progressive with considerable interindividual variability. Since 2001 two enzyme replacement therapies are approved which can possibly stop the disease progress and alleviate symptoms. The very few reports and clinical observations have shown that a very high proportion of FD patients develop neuropsychiatric symptoms. However, accurate data are lacking. Although the pathophysiologic mechanisms are quite unknown, it is surmised that sphingolipid deposits in the endothelium of small cerebral vessels lead to regional cerebral ischemia accompanied by neuropsychiatric symptoms and deficits. Furthermore, patients with FD are chronically distressed by pain attacks and additional somatic and psychological impairment. Frequently, pain attacks are triggered by psychosocial stress. The high interindividual variability can, thus, also be interpreted on the basis of existing stress and coping models. The present paper will review the presently available psychiatric and neuropsychological findings in FD and will discuss difficulties associated with classification and differential diagnosis of psychiatric disorders occurring in patients with FD.
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PMID:[Psychiatric and neuropsychological signs and symptoms in patients with fabry disease: literature review]. 1628 13

Hemophilia is an X-linked inherited bleeding disorder characterized by a deficiency of clotting factor VIII or IX in the intrinsic pathway of the coagulation cascade. This disease can have a profound, debilitating effect on the musculoskeletal system through recurrent hemarthroses and intermuscular hematomas. Although medical management with replacement factor is often effective, patients with severe hemophilia may develop chronic synovitis and arthropathy best treated with more invasive means. Radioactive synovectomy performed at select hemophilia centers and arthroscopic or open synovectomy are helpful for chronic, active synovitis. Arthroplasty helps improve function and pain relief for most patients, but complication rates, particularly for infection, are higher than those for arthroplasty performed on patients without hemophilia.
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PMID:Orthopedic management of hemophilia. 1630 95

Ehlers-Danlos syndrome is a rare inherited illness, which includes an autosomal dominant and also a recessive X-linked variant. Its main clinical characteristic is a generalised connective tissue involving collagen and elastin, causing fragile and hyperextensible skin, loose jointedness and bruising. Many clinical subtypes are described, each of a different severity degree pattern. The correlation of this syndrome and headache disorders is rare. In this paper we describe the case of a young woman with Type II (less severe) Ehlers-Danlos Syndrome and headache.
J Headache Pain 2005 Dec
PMID:Ehlers-Danlos syndrome: correlation with headache disorders in a young woman. 1638 46

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.
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PMID:The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease. 1660 77

Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation in lysosomes of the undegraded glycosphingolipids leads to a multi-system disease with dermatological, ocular, renal, cardiac, and neurological manifestations. Peripheral nerve involvement, neuropathic pain and chronic acroparesthesiae, are frequent and early-onset signs revealing the disease. They are due to the involvement of small nerve fiber, thus explaining the normality of electroneuromyography. Cochleo-vestibular and autonomic nervous system involvement is frequent. Besides rare aseptic meningitis, central nervous system involvement is essentially represented by cerebrovascular events (stroke, transient ischemic attack). Affecting essentially the posterior circulation, their etiologies have to be clarified: progressive stenosis of small vessels with globotriasocylceramide deposits, arterial remodeling, endothelial dysfunction, pro-thrombotic state, cerebral hypoperfusion consecutive to dysautonaumy, cardiac embolism. MRI shows numerous silent lesions, increasing with age, mainly in small perforant arteries (periventricular white matter, brainstem, cerebellum, basal ganglia). Pulvinar calcifications, due to an increase in cerebral hyperperfusion, could be specific of Fabry disease. Positon tomography analysis shows a reduced cerebral flow velocity and impaired cerebral autoregulation, secondary to the glycosphingolipid storage in vascular endothelial cells. Enzyme replacement therapy has to be carefully monitored.
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PMID:[Neurological aspects of Fabry's disease]. 1671 Jan 23

Anderson-Fabry disease is a rare inherited X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A. The deficiency of alpha-galactosidase activity leads to progressive, abnormal accumulation of neutral glycosphingolipids in the lysosome. With increasing age globotriaosylceramide (Gb3) progressively accumulates in different cells, tissues and organs throughout the body. The overall prevalence of Anderson-Fabry disease is 1:117.00 or 1: 40.000 in (male) population. Typically, the clinical onset of Anderson-Fabry disease occurs during childhood or adolescence, with early symptoms of neuropathic pain (recurrent episodes of severe pain in the extremities), angiokeratomas (characteristic cutaneous lesions), oedematous upper eyelids, peripheral vasospasm and ophthalmological abnormalities. The disease progresses through adulthood and by the age of 30-40 years several major organ systems may be affected; cardiac disease, renal insufficiency, cerebrovascular attacks and neurologic findings are common. Death usually occur secondary to renal, cardiac or cerebrovascular complications during the fourth or fifth decade of life. Enzyme replacement therapy is a major advance in the treatment of rare diseases. In 2001 two formulations have been approved by the European Medical Evaluation Agency, agalsidase alpha and agalsidase beta. Agalsidase alpha is produced on the human fibroblast cell line, and agalsidase beta from the Chinese hamster ovary cell line.
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PMID:[Anderson-Fabry disease]. 1680 73

Fabry disease is an X-linked lysosomal storage disorder characterized by multi-organ dysfunction, including hearing loss - mainly sensorineural. The recent introduction of enzyme replacement therapy (ERT) has resulted in improvements in renal and cardiac function, pain and quality of life. One study has also suggested small improvements in high-frequency hearing. In this paper, we study the effect of ERT on hearing in patients in the Europe-wide database - the Fabry Outcome Survey (FOS). Twenty-six patients in FOS had pure-tone audiometry performed up to 6 months before starting ERT with agalsidase alpha and after a median of 12 months of treatment. We assessed changes in hearing thresholds, expressed as deviations from the 50th centile of the normal population (International Organization for Standardization ISO 7029) to correct for age-related non-specific hearing deterioration. Hearing did not change significantly in ears with normal hearing (less than 10 dB deviation from the 50th centile of ISO 7029) or those with severe hearing loss (more than 40 dB deviation from the 50th centile of ISO 7029) at baseline. In ears with a mild or moderate hearing loss at baseline, hearing thresholds, expressed as deviations from the normal 50th centile, improved significantly by 4-7 dB at most frequencies (P < 0.05). Agalsidase alpha stabilizes, and possibly improves, hearing in Fabry patients who have not already progressed to severe hearing loss. Further follow-up of these patients will determine the longer-term effects of ERT.
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PMID:Agalsidase alpha and hearing in Fabry disease: data from the Fabry Outcome Survey. 1691 50

Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and hypohidrosis by the second decade of life reflecting disease progression in the peripheral and autonomic nervous systems. An insidious cascade of disease processes ultimately results in severe renal, cardiac, and central nervous system complications in adulthood. The late complications are the main cause of late morbidity, as well as premature mortality. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. The recent introduction of enzyme replacement therapy to address the underlying pathophysiology of Fabry disease has focused attention on the need for comprehensive, multidisciplinary evaluation and management of the multi-organ system involvement. In anticipation of evidence-based recommendations, an international panel of physicians with expertise in Fabry disease has proposed guidelines for the recognition, evaluation, and surveillance of disease-associated morbidities, as well as therapeutic strategies, including enzyme replacement and other adjunctive therapies, to optimize patient outcomes.
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PMID:Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. 1698 Aug 9

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon intravascular hemolytic anemia that results from the clonal expansion of hematopoietic stem cells harboring somatic mutations in an X-linked gene, termed PIG-A. PIG-A mutations block glycosylphosphatidylinositol (GPI) anchor biosynthesis, resulting in a deficiency or absence of all GPI-anchored proteins on the cell surface. CD55 and CD59 are GPI-anchored complement regulatory proteins. Their absence on PNH red cells is responsible for the complement-mediated intravascular hemolysis. Intravascular hemolysis leads to release of free hemoglobin, which contributes to many of the clinical manifestations of PNH including fatigue, pain, esophageal spasm, erectile dysfunction and possibly thrombosis. Interestingly, rare PIG-A mutations can be found in virtually all healthy control subjects, leading to speculation that PIG-A mutations in hematopoietic stem cells are common benign events. However, negative selection of PIG-A mutant colony-forming cells with proaerolysin, a toxin that targets GPI-anchored proteins, reveals that most of these mutations are not derived from stem cells. Recently, a humanized monoclonal antibody directed against the terminal complement protein C5 has been shown to reduce hemolysis and greatly improve symptoms and quality of life for PNH patients.
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PMID:New insights into paroxysmal nocturnal hemoglobinuria. 1712 35


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