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)

A new technique was utilized for the separation of neutral and acidic glycolipids using an equipment named U-Chamber System. This technique was employed for the chemical diagnosis of inherited inborn errors diseases in which complex glycolipids are involved. Results in the identification of storage products in Tay-Sachs' disease, GM1 gangliosidosis and Fabry's disease are presented.
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PMID:High performance thin layer chromatography of neutral and acidic glycolipids: application to the chemical diagnosis of lipid storage diseases. 41 92

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

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

Enzymatic determinations of the levels of lysosomal enzymes in serum or leukocytes samples have been carried out for the diagnosis of 7 sphingolipidosis. This methodology has allowed us to study 49 homozygotes and 33 close relatives at risk for the carrier state of a particular sphingolipidosis. So far we have diagnosed: 21 Gaucher's disease patients, 17 metachromatic leukodistrophy, 4 Niemann-Pick, 4 GM2 gangliosidosis, 2 Fabry and one GM1 gangliosidosis. Limitations in the performance and interpretation of the levels of the defective enzyme in heterozygotes, homozygotes and those variants not detected with the assays described are discussed.
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PMID:[Hereditary lysosomal diseases in Mexico. III. Laboratory diagnosis of sphingolipidosis]. 190 57

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

A new method is described for the detection of abnormal urinary oligosaccharide and glycopeptide excretion by thin layer chromatography and differential visualization of oligosaccharides and glycopeptides. This method permits rapid screening and identification of disorders characterized by oligosacchariduria and glycopeptiduria including alpha-N-acetylgalactosaminidase deficiency, angiokeratoma corporis diffusum with glycopeptiduria, aspartylglucosaminuria, galactosialidosis, fucosidosis, GM1 gangliosidosis and sialidoses 1 and 2. Of note, the characterization of the glycopeptide excretion profiles in patients with alpha-N-acetylgalactosaminidase deficiency and angiokeratoma corporis diffusum with glycopeptiduria revealed essentially identical patterns, indicating the metabolic relatedness of these two phenotypically distinct conditions. Use of this improved thin layer chromatographic method should enhance routine screening of patients for lysosomal storage diseases as well as permit the identification of new disorders resulting from defective oligosaccharide and/or glycoprotein metabolism.
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PMID:A method for the rapid detection of urinary glycopeptides in alpha-N-acetylgalactosaminidase deficiency and other lysosomal storage diseases. 220 41

A patient with severe deficiency of beta-galactosidase, who developed skin lesions of angiokeratoma corporis diffusum between the 3rd and 10th month of life, is described. The activity of other lysosomal enzymes, including alpha-neuraminidase, was normal. The first signs of the disease were noticed during the first month of life. By 3 months coarseness of the face and psychomotor retardation were present. In addition to angiokeratoma, he had large mongolian spots and several scattered slate-blue spots of pigmentation over his body. With the exception of the skin lesions, the other clinical signs and the course of the psychomotor deterioration were within the clinical picture of GM1 gangliosidosis, Type 1. Angiokeratoma, a manifestation of several lysosomal disorders, may appear in GM1 gangliosidosis during the first year of life.
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PMID:Angiokeratoma corporis diffusum in GM1 gangliosidosis, type 1. 250 16

During the last 5 years 2057 children under the age of 5 with various neurologic symptoms with the suspected diagnosis of lysosomal storage diseases were referred to our hospital from different universities and state hospitals. We were able to separate sphingolipidoses by lysosomal enzyme screening. A total of 300 patients (15%) with sphingolipidoses were diagnosed; there were deficiencies of arylsulfatase A [metachromatic leukodystrophy (MLD)] in 93 (31%), hexosaminidase [Sandhoff disease (SHD)] in 62 (20.7%), hexosaminidase A [Tay-Sachs disease (TSD)] in 15 (5%), beta-galactosidase (GM1 gangliosidosis) in 35 (11.7%), alpha-galactosidase (Fabry disease) in one (0.3%) cerebroside beta-galactosidase (Krabbe disease) in 65 (21.7%) and glucosylceramidase (Gaucher disease) in 29 (9.6%). SHD (20.7%), MLD (31%) and Krabbe disease (21.7%) were common. Prenatal enzymatic diagnosis was made in 70 at risk pregnancies, 64 for TSD and SHD, three for MLD and three for GM1 gangliosidosis by using chorionic villus biopsy in 54, cord blood samples in 12 and cultured amniotic fluid cells in four. Seventeen fetuses were found to be affected. We have calculated the relative frequency and minimum incidence of sphingolipidoses in Turkey. The combined incidence of sphingolipidoses is 4.615 per 100,000 live births. The calculated incidences are 1.43, 0.95, 1, 0.23, 0.54, 0.45, 0.015 per 100,000 live births for MLD, SHD, Krabbe, Gaucher, TSD, GM1 gangliosidosis and Fabry diseases, respectively. The real incidence, which covers all subtypes of this group of diseases, should be greater than this number. The results suggested that, as a group, sphingolipidoses are relatively common and represent an important health problem in Turkey and some rare autosomal recessive diseases of Turkey are due to 'founder effect' created by consanguineous marriages.
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PMID:Sphingolipidoses in Turkey. 1527 96

Cellular glycosphingolipid (GSL) storage is known to promote cholesterol accumulation. Although physical interactions between GSLs and cholesterol are thought to cause intracellular cholesterol "trapping," it is not known whether cholesterol homeostatic mechanisms are also impaired under these conditions. ApoA-I-mediated cholesterol efflux via ABCA1 (ATP-binding cassette transporter A1) is a key regulator of cellular cholesterol balance. Here, we show that apoA-I-mediated cholesterol efflux was inhibited (by up to 53% over 8 h) when fibroblasts were treated with lactosylceramide or the glucocerebrosidase inhibitor conduritol B epoxide. Furthermore, apoA-I-mediated cholesterol efflux from fibroblasts derived from patients with genetic GSL storage diseases (Fabry disease, Sandhoff disease, and GM1 gangliosidosis) was impaired compared with control cells. Conversely, apoA-I-mediated cholesterol efflux from fibroblasts and cholesterol-loaded macrophage foam cells was dose-dependently stimulated (by up to 6-fold over 8 h) by the GSL synthesis inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). Unexpectedly, a structurally unrelated GSL synthesis inhibitor, N-butyldeoxynojirimycin, was unable to stimulate apoA-I-mediated cholesterol efflux despite achieving similar GSL depletion. PDMP was found to up-regulate ABCA1 mRNA and protein expression, thereby identifying a contributing mechanism for the observed acceleration of cholesterol efflux to apoA-I. This study reveals a novel defect in cellular cholesterol homeostasis induced by GSL storage and identifies PDMP as a new agent for enhancing cholesterol efflux via the ABCA1/apoA-I pathway.
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PMID:Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator. 1589 Jun 46

Immunohistochemical studies of the presence of lactosylceramide (LacCer) in lysosomal storage disorders (LSDs) were done using anti-LacCer monoclonal antibody of the CDw 17 type (clone MG-2). No sign of an association between LacCer and the lysosomal system in normal cells was observed, except for histiocytes active in phagocytosis. A comparative study of a group of LSDs showed a general tendency for LacCer to increase in storage cells in Niemann-Pick disease type C (NPC), and types A and B, GM1 gangliosidosis, acid lipase deficiency, glycogen storage disease type II and mucopolysaccharidoses. LacCer accumulated in storage cells despite normal activity of relevant lysosomal degrading enzymes. The accumulation of LacCer displayed variability within storage cell populations, and was mostly expressed in neurons in NPC. An absence of the increase in LacCer in storage cells above control levels was seen in neuronal ceroid lipofuscinoses (neurons and cardiocytes) and in Fabry disease. Gaucher and Krabbe cells showed significantly lower levels, or even the absence, of LacCer compared with control macrophages. Results of immunohistochemistry were corroborated by semiquantitative lipid thin-layer chromatography (TLC). It is suggested that different associations of LacCer with the lysosomal storage process may reflect differences in glycosphingolipid turnover induced by the storage-compromised lysosomal/endosomal system.
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PMID:Lactosylceramide in lysosomal storage disorders: a comparative immunohistochemical and biochemical study. 1591 12


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