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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sphingolipidoses are caused by recessively inherited deficiencies of lysosomal hydrolases. The clinical backgrounds of and current biochemical and genetic approaches to the different forms and variants of gangliosidoses, trihexosylceramidosis (Fabry's disease), galactosylceramidosis (Krabbe's disease), sulfatidoses (metachromatic leukodystrophies), glucosylceramidosis (Gaucher's disease), sphingomyelinoses (Niemann-Pick disease) and ceramidosis (Farber's disease) are presented.
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PMID:Basic findings and current developments in sphingolipidoses. 10 96

An outline of the pathways of catabolism of four sphingolipids to ceramide, along with structural details of a few constituents, serves as a framework for better understanding of the sphingolipidoses. The four sphingolipids are sulfatide, sphingomyelin, globoside, and ganglioside GM1. Diseases which can be incorporated into the scheme include Niemann-Pick disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, ceramide lactoside lipidosis, Tay-Sachs disease, generalized gangliosidosis, Fabry disease, and Sandhoff disease. Fucosidosis probably also belongs with this group. GM3 (hematoside) sphingolipodystrophy involves blocks in synthetic rather than catabolic pathways.
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PMID:The sphiningolipidoses: an overview. 40 52

Fifteen patients with lysosomal storage diseases were studied. Diagnoses of their illnesses included infantile Gaucher disease; Krabbe disease; Niemann-Pick disease, type A; glycogen storage disease, type 3; Fabry disease, Jansky-Bielschowsky and Spielmeyer-Vogt types of amaurotic idiocy, GM1 gangliosidosis, type 1; Hurler disease; and Sanfilippo disease, types A and B. We carried out ultrastructural examinations of skin biopsy specimens that were taken to establish a cultured fibroblast line on each patient. We found diagnostic storage inclusions in all patients except those with infantile Gaucher disease, Krabbe disease, and Spielmeyer-Vogt disease, This technique can be carried out on a specimen obtained by a primary physician on an out-patient basis, thus avoiding major surgery.
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PMID:Lysosomal storage disorders. Diagnosis by ultrastructural examination of skin biopsy specimens. 80 24

We used a high-performance liquid chromatography method to measure CSF gangliosides, neutral glycolipids, and sulfatides in patients with lysosomal storage disorders. These measurements could be done on less than 1 milliliter of CSF. In patients with GM1 gangliosidosis, GM1 ganglioside was increased, and in GM2 gangliosidosis patients, GM2 ganglioside was increased in CSF. Sulfatides were variably increased in CSF early in the course of the disease and appeared to be a means of monitoring patients, following bone marrow transplantation. Fabry's disease patients showed an increase in globotriaosylceramide, but Krabbe's disease patients did not demonstrate an increase in galactosylceramide. This study suggests that CSF glycosphingolipid measurements may prove helpful in the diagnosis and monitoring of lysosomal storage diseases.
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PMID:Possible use of CSF glycosphingolipids for the diagnosis and therapeutic monitoring of lysosomal storage diseases. 146 81

Measurements were made of the pH of cytoplasm and lysosomes of cultured skin fibroblasts from healthy donors and from patients with lysosomal storage diseases (mannosidosis, Fabry's disease, and Krabbe's disease), and the effects of sucrose loading on normal fibroblasts were studied. The cytoplasmic pH of the pathological cells did not differ from control values, but the intralysosomal pH was significantly higher in sucrose-loaded normal fibroblasts and in cells from a patient with mannosidosis and from another with Fabry's disease. The change in pH observed accorded with an increase in size of the organelles, owing to accumulation of nonhydrolyzable compounds. In fibroblasts from a patient with Krabbe's disease, which do not store nonhydrolyzable compounds, there was no increase either in intralysosomal pH or in lysosome size. It is suggested that the decrease in the pH difference between the cytoplasm and lysosomes in the pathological cells leads to inhibition of catabolic processes in lysosomes and to some changes in the intracellular transport of these vesicles.
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PMID:Estimation and comparison of lysosomal and cytoplasmic pH of human fibroblasts from healthy donors and patients with lysosomal storage diseases. 179 44

Ultrastructural pathology on sweat gland epithelium was studied in various neurodegenerative disorders; neuronal ceroid-lipofuscinosis (NCL), Lafora disease, mucopolysaccharidosis, GM1 gangliosidosis, Nieman-Pick disease, Fabry disease, Krabbe disease and metachromatic leukodystrophy (MLD). Every disease had its own characteristic inclusions in sweat gland epithelium. Curvilinear profiles and fingerprint patterns were seen in NCL, but there were no morphological differences among late infantile, early juvenile and juvenile types. On the other hand, the granular matrix was characteristic of the infantile type. The presence of specific inclusions in a 23-year-old female carrier with Fabry disease indicated that a skin biopsy was one of the useful methods to detect a female carrier. In MLD and Krabbe disease, there were disease specific inclusions in sweat gland epithelium. These results indicate that the sweat glands should be investigated when a skin biopsy is performed for the diagnosis of neurodegenerative diseases.
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PMID:[Sweat gland pathology in neurodegenerative disorders]. 184 93

Presented are the results of measurements of pH in cytoplasm and lysosomes of skin fibroblasts of healthy donors and patients with lysosomal storage diseases, mannosidosis, Fabry, Krabbe disease. The pH value was estimated in the stationary phase of growth using neutral red (lysosomes) and fluorescein diacetate (cytoplasm). It was shown that the cytoplasmic pH value in pathological cells didn't virtually differ from the control values. The intralysosomal pH value in fibroblasts of patients with mannosidosis and Fabry disease was essentially increased, which correlated with the size increase of these organelles upon the accumulation of unsplit compounds. This led to the decrease in pH gradient between the cytoplasm and lysosomes in the pathological cells, an increase in intralysosomal pH along with hereditary deficiency of enzymes could bring about the retardation of catabolic processes in lysosomes.
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PMID:[Intravital determination of pH gradient between the cytoplasm and lysosomes in human fibroblasts in the normal state and in hereditary storage diseases]. 195 1

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

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


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