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)

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

Inherited metabolic disorders contribute importantly to adverse cardiovascular outcomes and affect all tissue types. This review summarizes some of the more important aspects. In the venous system, heterozygosities for the factor V Leiden and prothrombin 20210G > A mutations are common and occur in 4% and 1%, respectively, of caucasians. They confer a 2- to 3- fold increase in risk of venous, but not arterial, thrombosis. Marfan syndrome affects the systemic circulation and has a population prevalence of about 1 in 4000. The more than 200 mutations responsible are in the fibrillin-1 gene (15q21.1) and mediate the characteristic skeletal, lens and aortic changes. There are two potentially lethal inherited disorders of cardiac conduction, the long QT and Brugada syndromes. The prevalence for each is about 1 in 10,000. On the other hand, autosomal dominant hypertrophic cardiomyopathies are relatively common, at 1 in 500, but with variable penetrance. Mutations are in the sarcomere proteins and more than 140 are known. Hypertrophic cardiomyopathy may be confused with Fabry disease, for which effective treatment is now available. Mutations in several genes have been shown to produce dilated cardiomyopathy in the young, but there is as yet no specific treatment. In fatty acid oxidation disorders, arrhythmias and cardiomyopathy occur during acute decompensation. An important recently established cause of cardiomyopathy is carnitine transporter defect; it is treated effectively with oral carnitine. The autosomal dominant arrhythmogenic right ventricular dysplasia occurs with a prevalence of about 1 in 15,000 and presents with arrythmias and a dilated right ventricle. The mutations responsible have been mapped to chromosomes 1, 2, 10 and 14. Lysosomal storage disorders, the Ehlers-Danlos syndrome and other connective-tissue disorders affect cardiac valves and vessels. In addition to the relatively common inherited lipoprotein disorders familial hypercholesterolaemia and familial combined hyperlipidaemia, an important dominantly inherited lipid variable contributing to coronary risk is lipoprotein(a). The gene is localized to chromosome 6 and there is full expression in childhood. Elevated lipoprotein(a) levels contribute to the occurrence and severity of early-onset coronary disease and add to the already enhanced risk in patients with familial hypercholesterolaemia.
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PMID:Overview of inherited metabolic disorders causing cardiovascular disease. 1288 64

In men with classical Fabry disease (alpha-galactosidase A [alpha-Gal A] deficiency), kidney failure occurs as early as the second decade of life. In contrast, men with the mild "cardiac variant" have late-onset cardiac involvement and proteinuria but usually do not have renal failure. To investigate the nature of renal involvement in the cardiac variant of Fabry disease, the renal function and morphology were assessed in a 75-year-old affected man. He had mild congestive heart failure, a reduced left ventricular ejection fraction, and hypercholesterolemia but lacked the classical Fabry disease manifestations, including angiokeratoma, acroparesthesias, corneal and lenticular opacities, and hypohidrosis. At age 75 years, he had significant proteinuria, and mildly decreased renal function (serum creatinine, 1.8 mg/dL [159 micromol/L]), presumably secondary to hypertensive arteriosclerosis. He had about 4% residual alpha-Gal A activity in leukocytes, and mutation analysis identified the N215S missense mutation, the common lesion in cardiac variants. Histologic and ultrastructural studies of kidney tissue showed that lysosomal glycosphingolipid deposition was extensive in podocytes, rare in tubular epithelial cells, and absent in mesangial, interstitial, and vascular endothelial and smooth muscle cells. This cardiac variant serves as an "experiment of nature" showing that the residual alpha-Gal A activity precludes glycosphingolipid deposition in the renal endothelial and other cells that lead to early renal failure in classically affected men, whereas marked podocyte accumulation is associated with proteinuria and possibly late-onset renal dysfunction. These findings have important implications for the renal effectiveness of enzyme replacement therapy in classically affected patients and for the aggressive treatment of proteinuria in Fabry disease.
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PMID:Fabry disease: renal involvement limited to podocyte pathology and proteinuria in a septuagenarian cardiac variant. Pathologic and therapeutic implications. 1471 41

Cardiovascular survival in a cohort of 33 male Fabry patients followed for a median of 7.3 years at a single centre was most strongly associated in a Cox proportional hazard regression model with age and elevated arterial stiffness at baseline. Seven patients died of cardiovascular causes. The presence of cardiomyopathy and renal involvement (either clinical nephropathy or CKD stage >1) were also negatively associated with survival when analysed as single factors. In this small study, presence of hypertension and hypercholesterolemia at baseline did not significantly predict cardiovascular death. The significant effect of elevated arterial stiffness, especially in a small cohort, argues for its clinical utility in individual patient risk assessment and for further intervention studies focusing on therapeutic reduction.
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PMID:Increased arterial stiffness is associated with high cardiovascular mortality in male Fabry patients. 2216 76