Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.
J Neurochem 2001 Dec
PMID:Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease. 1175 62

Metabolic diseases are a rare cause of strokes. However, prevention and treatment are available for some of them. This work describes some metabolic diseases generating strokes by disturbing directly vascular function (homocysteine disorders, Fabry disease, congenital defects of glycosylation) and those for which clinical presentation is similar to a stroke (urea cycle disorders, branched-chain organic acidurias, mitochondrial diseases).
Rev Med Interne 2001 Dec
PMID:[Hereditary metabolic causes of stroke and pseudo-stroke in adulthood]. 1179 78

Anderson-Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal alpha-galactosidase A. Clinical manifestations of Anderson-Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson-Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson-Fabry disease affects both hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.
J Inherit Metab Dis 2001 Dec
PMID:Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes. 1180 8

We report the experimental observation of the frequency dependence of the photothermal effect. The measurements are performed by modulating the laser power absorbed by the mirrors of two high-finesse Fabry-Perot cavities. The results are very well described by a recently proposed theoretical model [M. Cerdonio, L. Conti, A. Heidmann, and M. Pinard, Phys. Rev. D 63, 082003 (2001)]], confirming the correctness of such calculations. Our observations and quantitative characterization of the dynamic photothermal effect demonstrate its critical importance for interferometric displacement measurements towards the quantum limit, as those necessary for gravitational wave detection.
Phys Rev Lett 2002 Dec 02
PMID:Experimental measurement of the dynamic photothermal effect in Fabry-Perot cavities for gravitational wave detectors. 1248 40

Fabry disease is an X-linked recessive disease with a reduction of lysosomal alpha galactosidase A and consecutive storage of glycolipids e.g., in the brain, kidney, skin, and nerve fibers. Cardinal neurologic findings are hypohidrosis, painful episodes, and peripheral neuropathy. So far, the neurophysiological findings regarding the extent of large and small fiber dysfunction are contradictory. This study evaluated large and small nerve fiber function in a homogeneous group of Fabry patients. In 24 of 30 Fabry patients with creatinine below 194.7 mmol/L the authors assessed median, ulnar, and peroneal motor conduction velocity (MCV) and median, ulnar, and sural sensory conduction velocity (SCV) nerve conduction to study the function of thickly myelinated nerve fibers. In addition, the authors studied sympathetic skin responses (SSR) at both hands and feet in 24 patients. To evaluate A beta nerve fiber function, the authors determined vibratory detection thresholds (VDT) at the first toe in 30 patients. Function of A delta and C fibers was assessed by quantitative sensory testing of cold detection threshold (CDT) and heat-pain detection thresholds (HPDT). Nerve conduction studies showed significantly decreased amplitudes of MCVs and SCVs in Fabry patients as compared to controls. However, individual results of MCV and SCV studies were only mildly impaired. SSRs were present in all tested patients but SSR amplitudes were significantly decreased in Fabry patients in comparison to controls. VDT, CDT, and HPDT were significantly elevated in Fabry patients as compared to controls. However, only six patients had pathologic VDT, 19 had increased CDT, and 25 had elevated HPDT at a high level of stimulation. In Fabry patients, small fiber dysfunction is more prominent than large fiber dysfunction, confirming previous findings of sural nerve biopsies. The results suggest a higher vulnerability of small-diameter nerve fibers than of the thickly myelinated fibers.
J Clin Neurophysiol 2002 Dec
PMID:Small fiber dysfunction predominates in Fabry neuropathy. 1248 89

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.
Z Kardiol 2002 Dec
PMID:Fabry disease in patients with hypertrophic cardiomyopathy (HCM). 1249 Sep 89

A mammalian-like sugar moiety was created in glycoprotein by Saccharomyces cerevisiae in combination with bacterial alpha-mannosidase to produce a more economic enzyme replacement therapy for patients with Fabry disease. We introduced the human alpha-galactosidase A (alpha-GalA) gene into an S. cerevisiae mutant that was deficient in the outer chains of N-linked mannan. The recombinant alpha-GalA contained both neutral (Man(8)GlcNAc(2)) and acidic ([Man-P](1-2)Man(8)GlcNAc(2)) sugar chains. Because an efficient incorporation of alpha-GalA into lysosomes of human cells requires mannose-6-phosphate (Man-6-P) residues that should be recognized by the specific receptor, we trimmed down the sugar chains of the alpha-GalA by a newly isolated bacterial alpha-mannosidase. Treatment of the alpha-GalA with the alpha-mannosidase resulted in the exposure of a Man-6-P residue on a nonreduced end of oligosaccharide chains after the removal of phosphodiester-linked nonreduced-end mannose. The treated alpha-GalA was efficiently incorporated into fibroblasts derived from patients with Fabry disease. The uptake was three to four times higher than that of the nontreated alpha-GalA and was inhibited by the addition of 5 mM Man-6-P. Incorporated alpha-GalA was targeted to the lysosome, and hydrolyzed ceramide trihexoside accumulated in the Fabry fibroblasts after 5 days. This method provides an effective and economic therapy for many lysosomal disorders, including Fabry disease.
Glycobiology 2002 Dec
PMID:Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease. 1249 4

The monitoring of interferometer fiber optic sensors using a laser that is scanned over a wide frequency range is investigated. The interrogation technique is based on the principle that if the light-source frequency varies linearly with time, the optical signal reflected or transmitted is intensity modulated at a frequency that is proportional to the optical path difference (OPD) in the interferometer. Fourier components in the detected optical output signal then correspond to the OPDs of any interferometers that have contributed to this modulation. The temporal position of a peak in the power spectrum of this signal is proportional to the OPD of the interferometer that is responsible for that peak. A fine tuning of the OPD value is determined from the phase of the corresponding Fourier component. Experimentally, an Er:fiber laser scanned over a 48-nm range centered at 1540 nm was used to monitor intrinsic fiber Fabry-Perot interferometers (FFPIs). Variations in the laser scan rate were compensated with the optical signal modulated by a reference FFPI held at a constant temperature. The OPD measurement resolution was 3.6 nm, and the dynamic range was 1.3 x 10(7). The temperature was measured from 20 degrees C to 610 degrees C with a 0.02 degrees C resolution, and multiplexing of three of the sensors arranged in series was demonstrated.
Appl Opt 2002 Dec 20
PMID:Monitoring and multiplexing technique for interferometric fiber optic sensors with a linearly chirped Er:fiber laser. 1251 Sep 27

Photonic band gap (PBG) materials are attractive for cavity QED experiments because they provide extremely small mode volumes and are monolithic, integratable structures. As such, PBG cavities are a promising alternative to Fabry-Perot resonators. However, the cavity requirements imposed by QED experiments, such as the need for high Q (low cavity damping) and small mode volumes, present significant design challenges for photonic band gap materials. Here, we pose the PBG design problem as a mathematical inversion and provide an analytical solution for a two-dimensional (2D) crystal. We then address a planar (2D crystal with finite thickness) structure using numerical techniques.
Phys Rev E Stat Nonlin Soft Matter Phys 2002 Dec
PMID:Inverse-problem approach to designing photonic crystals for cavity QED experiments. 1251 28

A male patient presented with oligosymptomatic Fabry disease (end stage renal failure and non-obstructive cardiomyopathy) at around 30 years of age. His leukocyte alpha-galactosidase activity (alpha-gal) was 2.6% of controls. A 50-year-old sister had similar cardiac symptoms and her asymptomatic heterozygous daughter (33 years) had normal enzyme activity. All three patients carried a novel, 6bp insertion on exon 7 of the AGAL gene. The majority of male Fabry patients carrying mutations in exon 7 have residual alpha-gal below 1% and suffer from neuropathic pain. Comparable oligosymptomatic phenotypes in Caucasian patients carry a common mutation on exon 6 (R301Q) and have a significantly later onset. The course of the disease is likely to be altered by recombinant enzyme therapy in the future. Therefore, a thorough documentation of phenotypes, residual activities and underlying genotypes is of current interest.
J Inherit Metab Dis 2002 Dec
PMID:A novel 6 bp insertion in exon 7 associated with an unusual phenotype in a family with Fabry disease. 1270 99


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