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)

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

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.
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PMID:A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody. 750 71

Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A. This deficiency leads to the progressive accumulation, in lysosomes of visceral tissues and in body fluids of hemizygotes, of the glycosphingolipids globotriaosylceramide (CTH, Gb(3) or GL-3) and galabiosylceramide (CDH) and to a lesser extent the blood group AB and B related glycolipids. Elevated levels of the glycosphingolipids are found in the urine of hemizygous males with the classic phenotype, but it is not known whether all symptomatic or asymptomatic heterozygotes have elevated levels. We have therefore measured CTH and CDH quantitatively in a multiplex assay using tandem mass spectrometry in urine from a large cohort (44) of genetically proven or obligate heterozygotes including four with the N215S mutation, from classic hemizygotes (28), from cardiac variant hemizygotes with the N215S mutation (6) and from normal controls. The levels of CTH and CDH were related to both creatinine and sphingomyelin. Urinary CTH was elevated in all 28 classic hemizygotes but only in 4/6 of the cardiac variants. The level was within or just above the normal reference range in the four individuals heterozygous for the N215S mutation but was elevated in 38/40 of the other heterozygotes. Similar results were obtained for CDH, except that only 34/40 heterozygotes had an elevated level. The level of CDH was not elevated in the four heterozygotes and 4/6 of the hemizygotes for the N215S mutation. Combining the levels of CTH and CDH did not improve the discrimination of heterozygotes from controls. The ratio of CDH to CTH was higher in heterozygotes than in hemizygotes. Measurement of urinary CTH gave the best discrimination of heterozygotes from controls.
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PMID:Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease. 1570 4