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)

We report a new assay for the detection of individuals heterozygous and homozygous for Gaucher's disease which requires relatively small samples of whole blood (0.3 ml), and which determines 4-methylumbelliferyl-beta-D-glucopyranoside:beta-glucosidase activity under conditions optimal for the determination of leukocyte glucocerebroside:beta-glucocereborsidase activity. The procedure involves the preparation of a leukocyte pellet from 50 mul of whole blood by hypotonic lysis of erythrocytes, followed by assay of beta-glucosidase activity at pH 5.5 in the presence of sodium taurocholate (0.6 g/100 ml). The methods described may also prove to be useful for the diagnosis of other diseases of enzyme deficiency which use fluorogenic substrates and leukocytes as a source of enzyme, such as Fabry's disease, Tay-Sachs disease, and generalized gangliosidosis.
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PMID:A microassay for Gaucher's disease. 80 4

Saposins (A, B, C, and D) are small glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Concentrations of these saposins in brain, liver, and spleen from normal humans as well as patients with lysosomal storage disease were determined. A quantitative HPLC method was used for saposin A, C, and D and a stimulation assay was used for saposin B. In normal tissues, saposin D was the most abundant of the four saposins. Massive accumulations of saposins, especially saposin A (about 80-fold increase over normal), were found in brain of patients with Tay-Sachs disease or infantile Sandhoff disease. In spleen of adult patients with Gaucher disease, saposin A and D accumulations (60- and 17-fold, respectively, over normal) were higher than that of saposin C (about 16-fold over normal). Similar massive accumulations of saposins A and D were found in liver of patients with fucosidosis (about 70- and 20-fold, respectively, over normal). Saposin D was the primary saposin stored in the liver of a patient with Niemann-Pick disease (about 30-fold over normal). Moderate increases of saposins B and D were found in a patient with GM1 gangliosidosis. Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease. The implications of the storage of saposins in these diseases are discussed.
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PMID:Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseases. 211 Mar 65

For the purpose of evaluating electron microscopy of tissue culture in making the diagnosis of sphingolipidoses, an ultrastructural study was made on the cultured fibroblasts from 23 patients with the disorders. The characteristic cytoplasmic inclusions were observed in the cultured cells of Fabry disease, Tay-Sachs disease, Sandhoff disease, generalized gangliosidosis, Niemann-Pick disease, metachromatic leukodystrophy, and multiple sulfatase deficiency, and differ in fine structure with these diseases. All these cytoplasmic inclusions were surrounded by a single limiting membrane and enzyme cytochemically showed acid phosphatase activity, indicating their lysosomal origin. Ultrastructurally, the cytoplasmic inclusions showed pleomorphic osmiophilic inclusions in Fabry disease, membranous cytoplasmic bodies (MCB) in Tay-Sachs disease and Sandhoff disease, MCB and vacuolar inclusions containing finely reticulogranular materials in generalized gangliosidosis, myelin-like inclusions in Niemann-Pick disease, concentric lamellar inclusions in metachromatic leukodystrophy, and polymorphic cytoplasmic inclusions in multiple sulfatase deficiency. In the heterozygous carriers of Fabry disease, pleomorphic osmiophilic inclusions were also detected. However, any specific inclusions were not detectable in the cultured fibroblasts of Gaucher disease and Krabbe disease. Availability of electron microscopy in the cultured fibroblasts of sphingolipidoses is discussed.
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PMID:Lipid storage disease: Part III. Ultrastructural evaluation of cultured fibroblasts in sphingolipidoses. 303 47

The lipids accumulated in organs of patients with Gaucher's, Tay-Sachs, and Fabry's disease were identified by means of the combination of thin-layer chromatography and matrix-assisted secondary ion mass spectrometry. The total lipid extract of each lipidosis tissue was chromatographed on a TLC plate and then analyzed directly by mass spectrometry without elution of the sample from the TLC plate. The amount of material needed to obtain an adequate spectrum is in the order of a few micrograms of lipids per band for both positive and negative ion detection. By scanning the plates, mass spectral and chromatographic information can be obtained simultaneously, which was shown to be useful for the qualitative identification of the components on the plates.
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PMID:Direct analysis of glycolipids on thin-layer plates by matrix-assisted secondary ion mass spectrometry: application for glycolipid storage disorders. 314 74

The nature of the metabolic defects in all of the major lipid storage diseases has been established within the past four years. This infromation has come primarily from extensive enzymologic studies in human tissues using labeled complex lipids as substrates. A brief description is presented of the background and experiments which led to the identification of the biochemical lesion in Gaucher's disease, Niemann-Pick disease, Fabry's disease, and Tay-Sachs disease.
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PMID:Biochemical approaches to the nosology of nervous system defects, II. 437 33

The eye provides unique opportunities for the detection, during life, of deposits of storage substances and other characteristic changes resulting from inborn metabolic defects. The cornea shows the macromolecular polysaccharides of Hurler's disease, the cystine crystals in cystinosis, and the copper deposits of Wilson's disease. The sclera shows characteristic pigmentation in alcaptonuria. The iris shows the lack of pigmentation in various types of albinism. The lens is cataractous in galactosemia and dislocated in homocystinuria. The vitreous is opacified in familial amyloidosis. The retina shows different and characteristic deposits with the diseases of Tay-Sachs, Niemann-Pick, metachromatic leukodystrophy, and Farber's lipogranulomatosis. The retinal veins show pronounced tortuosity with Fabry's disease. There is some evidence that optic neuropathy occurs in glucose-6-phosphate dehydrogenase deficiency. Curiously, few abnormalities in the eye have been described in subjects with the glycogen storage diseases.
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PMID:Ocular correlates of inborn metabolic defects. 533 50

Enzymatic, histochemical, and ultrastructural studies were performed on cultured skin fibroblasts from patients with Fabry's disease, Tay-Sach's disease, and Sandhoff's disease and from their families (carriers). alpha-Galactosidase activity was deficient in the proband with Fabry's disease (lower in the homozygotes than in the heterozygote). Levels of hexosaminidase A in the patient with Tay-Sachs disease and hexosaminidase A and B in the patient with Sandhoff's disease were deficient and were lower in her mother than in the control subject. Lysosome-like structures were observed in cultured fibroblasts from the patients with each disease, as well as in the heterozygote with Fabry's disease and the carrier with Tay-Sach's disease. The amount of the accumulating arrays in the lysosome-like structures was related to low level of enzymatic activity.
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PMID:Cultured skin fibroblasts in lipidoses. Enzymatic, histochemical, and ultrastructural relationship in Fabry's Tay-Sachs, and Sandhoff's diseases. 624 46

Concentrations of GL-la (glucocerebroside) (8.36 nmol/ml), GL-2a (lactosylceramide) (4.03 nmol/ml), GL-3a (globotriosylceramide) (2.25 nmol/ml) and GL-4a (globotetraosylceramide) (2.87 nmol/ml) have been determined in normal plasma and compared to concentrations in the plasma from patients with Gaucher, Krabbe, Fabry, Sandhoff and Tay-Sachs diseases as well as with hypercholesterolemia. HPLC analysis of perbenzoylated glycolipid derivatives (isolated and purified by modification of an existing procedure) was performed on samples equivalent to 50 to 100 microliter of plasma. The sensitivity could be readily increased ten-fold. We have employed a novel internal standard-monogalactosyl diglyceride, a plant glycolipid, commercially available in pure form. Analysis was performed on a 5 micron ultrasphere silica column, using a gradient of isopropanol in hexane rather than the more usual dioxane in hexane. Our gradient exhibited an essentially flat baseline precluding the necessity of a reference cell. Recoveries of glycolipids added to plasma (95%), experimental yields (60%) and standard curves are presented and discussed. A method is also presented for the separation of GL-la and monogalactosyl diglyceride derivatives for rapid (8 minute) isocratic analysis of multiple samples from Gaucher patients. The benefits of such a simple, reproducible HPLC technique are discussed.
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PMID:HPLC analysis of neutral glycolipids: an aid in the diagnosis of lysosomal storage disease. 661 61

Lysosomal acid hydrolase activities have been measured in extracts of peripheral blood leucocytes of approximately 1600 patients referred from throughout Australia, each of whom was suspected of having a neurolipidosis. Assays for 12 different lysosomal enzymes were performed on each patient as a routine; ten assay systems were based on commercially available substrates, and four used radiolabelled glycosphingolipids prepared in our own laboratory. Of the 85 patients with positive results, 81 were diagnosed as being homozygous-deficient for a particular lysosomal enzyme. These patients comprised nine with GM1-gangliosidosis, 12 with GM2-gangliosidosis (11 of Tay-Sachs' disease and one of Sandhoff's disease), 18 with trihexosylceramide lipidosis (Fabry's disease), eight with beta-galactosylceramide lipidosis (Krabbe's disease), 14 with beta-glucosylceramide lipidosis (Gaucher's disease), two with sphingomyelin lipidosis (Niemann-Pick disease), 13 with metachromatic leucodystrophy and five with alpha-mannosidosis. In addition, four patients were diagnosed as being affected with mucolipidosis Type II (I-cell disease), based on elevated plasma lysosomal enzyme activities, making a total of 85 homozygous-affected patients. Clinically the patients showed wide phenotypic variability within each of the enzyme-deficient states, which did not appear to correlate with the level of "residual" enzyme activity in their leucocyte extracts.
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PMID:Enzymological diagnosis of a group of lysosomal storage diseases. Review of 5-year experience of 1600 patient-sample referrals. 678 Jul 72

The combined use of immunofluorescence method with oligosaccharide-specific monoclonal antibodies against glycolipids and a confocal laser scanning microscopic system was successful to detect the storage of glycolipids in cultured cells derived from patients with lysosomal diseases. The accumulated glycolipids were observed stereoscopically as granular inclusions in the cells. An immunofluorometric semiquantative determination was achieved of globotriaosylceramide in cultured fibroblasts from Fabry disease patients or GM2-ganglioside in cultured amniocytes from Tay-Sachs disease. Heterozygote identification of the former disease or prenatal diagnosis of the latter one were confirmed by counting immunoreactive cells or by digital imaging analysis. The present immunofluorescence method is applicable to the diagnosis of the other lipidosis with accumulation of the specific glycolipids.
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PMID:[Glycolipid analysis by confocal laser scanning microscopic system]. 857 65


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