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)

Six pregnancies of three carriers for X-linked Fabry's disease, were monitored by chromosome and enzyme analysis. Two affected male fetuses were detected by the demonstration of alpha-galactosidase deficiency in amniotic fluid cells and chorionic villi respectively. The use of chorionic villi enabled a diagnosis within a few hours after sampling in the ninth week of pregnancy whereas the use of amniotic fluid cells in the earlier case required two weeks of culturing after amniocentesis in the 16th week. Four female fetuses were found; heterozygosity was demonstrated in one by analysis of clones in the primary amniotic fluid cell culture.
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PMID:Prenatal diagnosis of Fabry's disease by direct analysis of chorionic villi. 303 32

A procedure is described for the intrauterine detection, at the 17th week of gestation, of a male fetus afflicted with Fabry's disease. The validity of this determination was substantiated by multiple enzyme and lipid analyses of tissue specimens obtained from the afflicted fetus. Fabry's disease may now be included with other X-linked metabolic deficiency diseases that are amenable to precise genetic counseling, through carrier identification, and the monitoring of ensuing pregnancies.
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PMID:Fabry's disease: antenatal detection. 554 32

A pilot trial of enzyme replacement using splenic and plasma forms of alpha-galactosidase A was undertaken in 2 brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Partially purified preparations of alpha-galactosidase A from human spleen and plasma Cohn fraction IV-1 were prepared aseptically for in vivo administration. The disappearance of enzymatic activity from plasma, levels of circulating substrate, and potential immune response were evaluated following IV administration of 6 unentrapped doses (2,000 U/kg) of each enzyme form to the respective recipient during a 117-day period. Repeated injections were well tolerated. The circulating half-life of the splenic form was about 10 min whereas that for the plasma form was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either enzyme following successive administrations. After each dose of the splenic form, the concentration of the accumulated circulating substrate globotriaosylceramide, decreased maximally (approximately 50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma form decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations of globotriaosylceramide gradually returned to preinfusion values by 36-72 hr. Two consecutive doses of the plasma form, administered on days 1 and 3, reduced the circulating substrate concentration to normal levels. Prior to the 6th enzyme administration, circulating substrate was stable-isotope labeled by the infusion of dideutero-glucose, and the effects of each enzyme form on circulating substrate degradation and reaccumulation were determined. The results of this study indicated that labeled (newly synthesized) substrate reaccumulated following injection of the splenic enzyme whereas both unlabeled (previously stored?) and labeled substrate reaccumulated in the circulation after administration of the plasma form. These studies demonstrated the differential disappearance kinetics of the splenic and plasma forms of alpha-galactosidase A, their differential effects on circulating substrate degradation and reaccumulation, as well as the lack of an immune response to repeated administrations of these homologous, unentrapped enzymes.
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PMID:Enzyme therapy XVII: metabolic and immunologic evaluation of alpha- galactosidase A replacement in Fabry disease. 625 19

In Fabry disease, as in other X-linked traits, identification of all heterozygotes is difficult. Reduced plasma alpha-galactosidase activities will correctly identify 60-70% of the carriers. The identification rate improves when an alpha/beta-galactosidase activity enzyme ratio is used. We measured alpha-galactosidase activity in reference to several other enzyme activities, beta-galactosidase, beta-hexosaminidase, and alpha-fucosidase in plasma and leukocytes from 22 suspected and 9 obligate carriers from 4 kindreds of Fabry disease patients. Utilizing such ratios or various combinations of ratios in plasma we have correctly identified the carrier state in 91% of heterozygotes. Leukocyte alpha/beta-galactosidase identified one more female than leukocyte alpha-galactosidase activities alone. We recommend the use of such multiple biochemical tests to identify carriers of Fabry disease.
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PMID:Heterozygote detection in Fabry disease utilizing multiple enzyme activities. 627 91

Apparent deficiency of alpha-galactosidase A was observed in a 51-year-old, clinically healthy male, with no clinical symptoms of Fabry disease, and without excess urinary excretion of ceramide trihexoside. The deficiency, which was similar to that found in Fabry disease patients, could be demonstrated using both synthetic and natural substrates. This pseudodeficiency was transmitted in his family by classical X-linked inheritance. His wife showed enzyme activity in the normal range, two daughters were heterozygotes for this mutation as demonstrated by hair root assay, and three sons showed normal alpha-galactosidase activity. Kinetic studies in cultured skin fibroblasts indicated a five-fold increase in the apparent Km and a greater heat stability of the residual alpha-galactosidase activity when compared to controls. These data indicate that the residual enzyme activity in this mutation behaves similarly to that observed in Fabry disease patients but does not cause any clinical abnormalities.
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PMID:Pseudodeficiency of alpha-galactosidase A. 627 39

Fabry disease is an X-linked sphingolipid disorder that is manifest clinically as a disease of nerves, kidneys, and blood vessels. Precise identification of Fabry heterozygotes is essential for genetic counseling. Heterozygote detection by enzyme assay does not consistently distinguish them from unaffected females. We describe a method for Fabry heterozygote detection, based on quantitation of urinary sediment glycolipids by high-performance liquid chromatography. In specimens from 12 Fabry heterozygotes, the total glycolipid fraction was increased (10 to 100-fold) and trihexosyl ceramide (CTH) was 2- to 70-fold times normal. Digalactosyl ceramide (Digal-Cer), which is normally present in trace amounts in urine, was also increased. The ratio of CTH and Digal-Cer to hydroxy fatty acid glucosyl ceramide was increased and seemed to be characteristic of Fabry disease. This method provides rapid and accurate detection of Fabry heterozygotes.
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PMID:Fabry disease: detection of heterozygotes by examination of glycolipids in urinary sediment. 628 88

The first part of this review deals with the new biochemical and genetical data concerning alpha-galactosidase and alpha-N-acetylgalactosaminidase. Molecular forms of these both enzymes can be classified into two groups following their physical, enzymatic and genetical properties: - the 3 forms of the alpha-galactosidase A group differ by the number of sialyl residues and their isoelectric point. All the forms of this group are heat-labile, hydrolyse only alpha-galactosides and proceed from the same alpha-GalA, X-linked gene. - alpha-galactosidase B is an alpha-N-acetylgalactosaminidase with broad substrate specificity, in vitro, is heat-stable and proceed from the alpha- GalB or alpha- NAGA gene of the chromosome 22. Structural and enzymatic data concerning these enzymes and their functions in the catabolism of glycosphingolipids and glycoproteins are reviewed. The second part deals with the pathophysiology of Fabry disease. The more prominent genetical and biochemical data and their diagnostic uses are reported: isozymic determination, cell cloning, quantitative determination of accumulated glycolipids. At last, were pointed the new developments of the research on Fabry disease: cultured cells as experimental model (fibroblasts, lymphoid cell lines) and therapeutic attempts.
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PMID:[Alpha-galactosidases and alpha-N-acetylgalactosaminidase. Biochemical bases of Fabry's disease]. 632 22

Cell sorting is a way to isolate viable subpopulations of cells present in a mixture. The drawback of the isolation method is the shortage of material for subsequent biochemical determinations. We have employed a combination of (ultra-) microchemistry and cell sorting to overcome this problem. The methods enable determinations of protein and several enzyme activities on triton extracts of 5,000-10,000 sorted cells. In addition, using ultramicromethods we could determine enzyme activity in single sorted cells. This combination of methods is used for clinical genetic studies on heterozygote detection in Fabry's disease, an X-linked genetic disease. Moreover, microchemistry is used to study enzyme activities in sorted autofluorescent "aged" fibroblasts.
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PMID:Cell sorting and microchemistry of cultured human fibroblasts: applications in genetics and aging research. 642 24

In X-linked inheritance, the difference between the terms dominant and recessive is blurred by the Lyon effect. In some X-linked recessive genodermatoses, the Lyon effect makes the detection of heterozygote females possible, either by clinical cromanifestations or by enzymatic demonstration of two functionally different populations of cells. The gene locus of X-linked recessive ichthyosis, however, escapes X-inactivation, but heterozygotes can be detected by enzyme analysis in this condition, too. X-linked dominant gene defects with manifestation in both sexes include keratosis follicularis spinulosa decalvans, and probably also the Bazex syndrome. The group of X-linked dominant gene defects with lethality in the male comprises incontinentia pigmenti, focal dermal hypoplasia, the oral-facial-digital syndrome and the CHILD syndrome. Prenatal diagnosis of severe X-linked conditions can be performed when the underlying defect of cell function is known (Fabry disease, Menkes syndrome). In other severe X-linked disorders, the possibility of prenatal determination of the sex may be considered (Wiskott-Aldrich syndrome, X-linked dominant chondrodysplasia punctata, oral-facial-digital syndrome).
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PMID:[X-chromosome-linked hereditary dermatoses]. 680 14

Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A (alpha-Gal A) gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder-variant Fabry phenotypes, and for precise carrier detection in Fabry families, the alpha-Gal A transcripts or genomic sequences from unrelated Fabry hemizygotes were analyzed. In patients with the classical phenotype, 18 new mutations were identified: N34S, C56G, W162R, R227Q, R227X, D264V, D266V, S297F, D313Y, G328A, W340X, E398X, IVS2+2, IVS5 delta-2,3, 773 delta 2, 954 delta 5, 1016 delta 11, and 1123 delta 53. Unrelated asymptomatic or mildly affected patients with symptoms confined to the heart had a missense mutation, N215S, that expressed residual enzymatic activity. Related, moderately affected patients with late-onset cardiac and pulmonary manifestations had a small deletion, 1208 delta 3, that predicted the in-frame deletion of arginine 404 near the terminus of the 429 residue enzyme polypeptide. In addition, five small gene rearrangements involving exonic sequences were identified in unrelated classically affected patients. Two small deletions and one small duplication had short direct repeats at their respective breakpoint junctions and presumably resulted from slipped mispairing. A deletion occurred at a potential polymerase alpha arrest site, while the breakpoints of another deletion occurred at an inverted tetranucleotide repeat. Screening of unrelated Fabry patients with allele-specific oligonucleotides for seven mutations revealed that these were private, with the notable exception of N215S, R227Q, and R227X, which were each found in several unrelated families from different ethnic backgrounds. The CpG dinucleotide at codon 227 was the most common site of mutation, having been altered in 5% of the 148 unrelated Fabry alleles. These studies revealed that most alpha-Gal A lesions were private, that codon 227 was a mutational hot spot, and that certain mutations predicted a milder disease phenotype.
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PMID:Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. 750 5


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