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's disease is a glycosphingolipid storage disease associated with premature generalized arteriosclerosis. Plasma low density lipoprotein (d 1.019--1.055 g/ml; LDL) was isolated from 4 healthy male volunteers (LDL-N) and from 4 patients with Fabry's disease (LDL-F), in whom plasma globotriaosylceramide (GbOse3) levels were 2--4 times above normal. LDL-N was labeled with 131I and LDL-F with 125I by the iodine monochloride method; both were then injected together intravenously into 4 mongreal dogs. The rates at which they were metabolized were determined by measuring plasma radioiodine levels daily for 7--8 days. No significant difference (Fisher's F-test) was observed between LDL-N and LDL-F in terms of the size of the intravascular compartments (LDL-N, 86.3 +/- 4.2%;; LDL-F, 94.2 +/- 7.7%), biological half-lives (LDL-N, 24.1 +/- 4.2 h; LDL-F, 23.5 +/- 3.7 h), or fractional catabolic rates (LDL-N, 0.849 +/- 0.066; LDL-F, 0.796 +/- 0.070). The results indicate that significant abnormalities of the neutral glycosphingolipid composition of LDL, such as occur in Fabry's disease, do not affect the metabolism of the lipoprotein apoprotein in dogs. The arteriosclerosis in patients with the disease is probably due to damage to vessel walls occurring as a result of defective GbOse3 metabolism and accumulation of glycosphingolipid in the tissue, rather than to abnormal LDL metabolism.
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PMID:Stability of plasma low density lipoprotein with abnormal glycolipid composition from patients with Fabry's disease. 676 8

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

The identification of stroke cases caused by monogenic disorders is important both for therapeutic decisions and genetic counselling, although they represent less than 1% of all stroke patients. The purpose of this review is to summarize genetic, pathological, and clinical features of single-gene disorders related to ischemic stroke. The following monogenic disorders are considered: cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal-recessive arteriosclerosis with subcortical infarcts and leukoencephalopathy, hereditary endotheliopathy with retinopathy, nephropathy, and stroke, Fabry disease, pseudoxanthoma elasticum, Neurofibromatosis type 1, familial MoyaMoya disease, Ehlers-Danlos syndrome type IV, Marfan syndrome. For each monogenic disorder, mode of inheritance, pathophysiological aspects, clinical phenotype, and diagnostic tools are carefully described. Furthermore, the classification of monogenetic disorders is presented according to stroke mechanisms, which include small vessel diseases, large artery diseases, and arterial dissections. This review could be useful to identify specific diagnostic pathways for patients with a suspicion of monogenic disease.
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PMID:Monogenic vessel diseases related to ischemic stroke: a clinical approach. 1757 57