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)

1. Presentation of the commomly used procedures for the extraction and separation of total lipids, glycolipids and phosholipids from fresh and formalin-fixed organs tissues (brain, liver, spleen, kidney) as well as from serum, CSF and urine. II. Description of the qualitative and quantitative analysis of individual lipid fractions (glycolipids, gangliosides, phospholipids, neutral lipids) by thin-layer chromatograhy and photodensitometry. III. Results of investigations performed on biopsy material, autopsy material, serum and urine in the following diseases: 1. Infantile, juvenile and adult Gaucher's disease: accumulation of glucocerebroside in liver and spleen. 2. Infantile and adult Niemann-Pick disease: accumulation of sphingomyelin in liver, spleen, kidney and lung. 3. Fabry's disease: increased urinary excretion of trihexosyl-ceramide and dihexosyl-ceramide. 4. Infantile and adult metachromatic leukodystrophy: accumulation of sulfatides in the central and peripheral nervous system and kidney, increased urinary excretion of sulfatides. 5. Austin's variant of metachromatic leukodystrophy: besides an increase of sulfatides in the white matter of brain accumulation of glycolipids in the cerebral cortex. 6. Tay-Sachs disease (GM2-gangliosidosis): cerebral accumulation of GM2-ganglioside and trihexosylceramide (enzyme variant B), additional visceral accumulation (liver, spleen, kidney) of tetrahexosyl-ceramide = globoside (enzyme variant 0). 7. Infantile generalized GM1-gangliosidosis: cerebral (and visceral) accumulation of GM1-ganglioside and tetrahexosyl-ceramide. 8. Late infantile GM1-gangliosidosis: Cerebral accumulation of GM1-ganlioside and tetrahexosylceramide. 9. GM3-gangliosidosis (lactosyl-ceramidosis): neuronal accumulation of lactosyl-ceramide, GM2-ganglioside and GM3-ganglioside. 10. Refsum's disease: demonstration of phytanic acid esters of cholesterol in serum.
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PMID:[Differential diagnosis of congenital lipidoses by lipid analyses of body fluids, biopsy and autopsy tissue]. 5 74

The ranges of variability of eight lysosomal acid hydrolases were examined in 47 cultured human skin fibroblast lines through 5 successive subcultures. No overall trend in activity values was found for any of the enzymes tested between the first and final subcultures. Similarly, no significant differences could be found between the overall ranges of fibroblast enzyme activity between 20 clinically normal children and 27 individuals being investigated for non-specific metabolic diseases. It is concluded that for diagnostic reference purposes, wide ranges of normal enzyme values must be established. Such ranges can be validly drawn from a continuation of both clinical groups irrespective of the passage number (up to 5) of the cells at the time of isolation. It is noted that in certain cell lines derived from Fabry and Gaucher patients the 'residual' activity of the expectedly deficient enzyme could not easily be distinguished from the lowest values observed in normals, whereas, as expected, the activity of cells derived from patients with GM1 and GM2 gangliosidoses was markedly reduced.
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PMID:Variability of fibroblast lysosomal acid hydrolases with reference to the detection of enzyme deficiencies. 41 Mar 98

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

This paper reports the ultrastructural findings for the epidermis of biopsied skin specimens in numerous lysosomal diseases, which can be grouped as follows: a) presence of vacuolar lysosomal residual bodies in mucopolysaccharidoses I, II and III, Salla disease, GM1-gangliosidoses and infantile type II glycogenosis; b) avacuolar lysosomal residual bodies in Niemann-Pick disease type C, mucolipidosis IV, Farber disease, Fabry disease, and late infantile and juvenile neuronal ceroid-lipofuscinoses; c) absence of lysosomal residual bodies in GM2-gangliosidoses, metachromatic leukodystrophy, Gaucher disease and sialidosis type III. Whenever possible, a biopsy of the skin for morphological diagnosis of lysosomal disorders ought not to be confined to the epidermis.
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PMID:Intraepidermal morphologic manifestations in lysosomal diseases. 255 41

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

Lysosomal storage disorders (LSDs), over 40 different diseases, are now considered treatable disorders. Only a few short years ago, Lysosomal storage disorders were seen as interesting neurodegenerative disorders without any potential for treatment. Effective treatment strategies such as bone marrow transplantation (BMT), enzyme replacement therapy (ERT), and glycolipid synthesis inhibition have been developed in the last 20 years and continue to be researched and evaluated. Bone marrow transplantation began approximately 15 years ago and has shown benefit for some of the lysosomal storage disorders. In order to be effective, the transplant must be performed early in the course of the disease, before the development of irreversible neurologic damage. Diseases such as Hurler appear to respond to BMT, however, improvement in bone disease is much less vigorous than responses in other organs. Krabbe disease responds if the transplant is performed before irreversible signs of neurologic damage appear. Metachromatic leukodystrophy may respond if the transplant can be performed early enough although peripheral nerve findings appear to progress. Other diseases, eg, GM1- and GM2-gangliosidoses do not appear to be altered by BMT. Despite its high cost, ERT has been very effective treatment for type I (non-neuronopathic) Gaucher disease. Enzyme replacement therapy for other LSDs, including ERT for Fabry and Pompe diseases, which are planned to be imminently introduced, and other enzymes such as for Morquio and Hunter diseases that are in the study phases, may be marketed in the very near future. Glycolipid inhibitors, such as N-butyldeoxynijirimycin (OGS-918), have been effective in reducing the liver and spleen volume in type I Gaucher disease. These oral inhibitors may prove to be important adjuncts to ERT and provide the advantage of being able to cross the blood/brain barrier, which limits enzyme access to brain. Currently, clinical studies are being conducted on patients with type III Gaucher disease and Fabry disease using OGS-918. Other, potentially more specific, glycolipid inhibitors are being developed.
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PMID:Lysosomal Storage Diseases. 1128 40

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders individually considered as rare, and few data on its prevalence has been reported in the literature. The overall birth prevalence of the 29 different LSDs studied in the Portuguese population was calculated to be 25/100000 live births, twice the prevalence previously described in Australia and in The Netherlands. The comparison of the prevalence profile of the LSDs presenting a prevalence higher than 0.5/100000 in the Portuguese, Dutch and Australian populations showed, in the Portuguese, the existence of a higher prevalence of GM2 gangliosidoses (B variant), mucolipidoses (II and III), Niemman-Pick type C and metachromatic leukodystrophy (MLD), and a lower prevalence of Pompe and Fabry. The highest prevalence value for a single LSD is the one of GM2 gangliosidoses (B variant), corresponding to 3/100000, a value which is significantly higher than the prevalence of the most frequent LSD in Dutch, Pompe disease (2/100000) and Australians, Gaucher's disease (GD) (1.8/100000). It is worth noting that the highest prevalence of GM2 gangliosidoses found in the Portuguese is mainly due to the existence of a unique subtype, the rare juvenile B1 variant.
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PMID:Prevalence of lysosomal storage diseases in Portugal. 1468 53

Lysosomal diseases represent a large group of genetic storage disorders characterized by a defect in the catabolism of complex molecules within the lysosome. Effective treatments are now possible for some of them given progresses in bone-marrow transplantation, enzyme replacement therapy and substrate reduction therapy. Neurologists and psychiatrists are concerned by these diseases because they can present in adolescence or adulthood with progressive neuropsychiatric signs. Here we focus on late-onset clinical forms which can be met in an adult neurology or psychiatric department. Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography.
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PMID:[Neurological presentations of lysosomal diseases in adult patients]. 1803 28

The sphingolipidoses are a group of inherited lysosomal storage diseases in which sphingolipids accumulate due to the defective activity of one or other enzymes involved in their degradation. For most of the sphingolipidoses, little is known about the molecular mechanisms that lead to disease, which has negatively impacted attempts to develop therapies for these devastating human diseases. Use of both genetically-modified animals, ranging from mice to larger mammals, and of novel cell culture systems, is of utmost importance in delineating the molecular mechanisms that cause pathophysiology, and in providing tools that enable testing the efficacy of new therapies. In this review, we discuss eight sphingolipidoses, namely Gaucher disease, Fabry disease, metachromatic leukodystrophy, Krabbe disease, Niemann-Pick diseases A and B, Farber disease, GM1 gangliosidoses, and GM2 gangliosidoses, and describe the tools that are currently available for their study. This article is part of a Special Issue entitled Tools to study lipid functions.
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PMID:From sheep to mice to cells: tools for the study of the sphingolipidoses. 2460 65


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