Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutral glycosphingolipids from urinary sediments of six patients with Fabry's disease and 11 members of the family of one propositus were analyzed using high-performance liquid chromatography. Per-o-benzoyl derivatives of GlcCer, LacCer, GbOse3Cer and GbOse4Cer were clearly resolved by a solvent mixture of hexane/dioxane/isopropanol (75:25:1, v/v) on a normal-phase silica column. Using our isocratic solvent system, the analysis was completed within 15 min. The smallest amount of glycolipid that could be detected by HPLC was 50 pmol and a linear response was shown at 230 nm up to 400 pmol. The calculated peak area of GbOse4Cer was higher than those of GlcCer, LacCer and GbOse3Cer. The molar ratios of GbOse3Cer to monohexosyl ceramide (CMH) in the urinary sediments were: Fabry hemizygotes, 36.33 +/- 25.54 (n = 6); heterozygotes, 0.94 +/- 0.50 (n = 4); and controls, 0.11 +/- 0.06 (n = 5). The molar ratio CDH/CMH was also higher in patients (8.42 +/- 6.23) than in controls (0.77 +/- 0.23). The female H was a rare example of a carrier with typical clinical manifestations. From the urinary sediment analysis, females E, G and J were suspected to be Fabry heterozygotes, although no clinical signs were observed at the time of examination.
 ...
PMID:Urinary neutral glycosphingolipid analysis of patients with Fabry's disease; rapid isocratic elution from high-performance liquid chromatography as per-o-benzoyl derivatives. 210 77

The content of glycosphingolipids (GSL) was studied in the urinary sediments (24-hr specimens) from seven normal subjects, a patient with Fabry's disease, and five homozygotes with familial hypercholesterolemia (FH). Normal urinary sediments contained very small amounts of GalCer, GlcCer, GaOse(2)Cer, LacCer, GbOse(3)Cer, and GbOse(4)Cer. In Fabry urinary sediment, the levels (nmole glucose/24 hr) of GaOse(2)Cer and of GbOse(3)Cer were 389 and 550, respectively. In urinary sediments from the FH subjects, the mean contents (nmol glucose/mg protein per 24 hr) of GlcCer, GalCer, and LacCer were 2.7, 1.9, and 15.8 times higher, respectively, than in normals. The mean contents ( micro g/mg protein per 24 hr) of total cholesterol and phospholipid in the urinary sediment of FH (1.1 and 224, respectively) and normals (0.8 and 220) were similar. The mean contents of GlcCer, GalCer, and LacCer, expressed in terms of the cholesterol content of urinary sediment (nmol glucose/ micro g cholesterol per 24 hr), were increased 3.4-, 1.6-, and 5.4-fold, respectively, in the FH homozygotes. Of the five FH homozygotes, only one, who had undergone a portacaval shunt and was also receiving lipid-lowering therapy, had a normal value of LacCer. The other four FH homozygotes had levels of LacCer that were 3- to 55-fold higher (nmol glucose/mg protein per 24 hr) and 5.5- to 7.3-fold higher (nmol glucose/ micro g cholesterol per 24 hr) than the mean of the normals. One homozygote underwent plasma exchange therapy that reduced both the baseline urinary (nmol glucose/24 hr) and plasma (nmol/100 ml) LacCer levels from 86 to 7 and from 1491 to 852, respectively. Eleven days after plasma exchange, the urinary LacCer levels approached pre-exchange levels (59 nmol glucose/24 hr). The data indicate that there is an abnormality of GSL metabolism associated with familial hyper-cholesterolemia and that the urinary excretion of GSL can be modified by plasma exchange therapy.-Chatterjee, S., C. S. Sekerke, and P. O. Kwiterovich, Jr. Increased urinary excretion of glycosphingolipids in familial hypercholesterolemia.
 ...
PMID:Increased urinary excretion of glycosphingolipids in familial hypercholesterolemia. 680 69

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.
 ...
PMID:Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease. 1570 4