Disease relevance of Fabry Disease

• 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 [1].
• Angiokeratoma corporis diffusum (Anderson-Fabry disease) in a single large family in Nova Scotia [2].
• RESULTS: A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease [3].
• Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection [3].
• In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease [4].

High impact information on Fabry Disease

• Improvement in cardiac function in the cardiac variant of Fabry's disease with galactose-infusion therapy [5].
• We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease [6].
• We identified a novel mutation of alpha-Gal A gene in a family with Fabry disease, which converted a tyrosine at codon 365 to a stop and resulted in a truncation of the carboxy (C) terminus by 65 amino acid (AA) residues [7].
• Southern hybridization analysis of the alpha-galactosidase gene in affected hemizygous males from 130 unrelated families with Fabry disease revealed six with different gene rearrangements and one with an exonic point mutation resulting in the obliteration of an Msp I restriction site [8].
• No significant elevation of plasma or leukocyte alpha-galactosidase activities above levels in untreated men with Fabry's disease or decrease in the levels of trihexosyl ceramide was observed in either patient [9].

Chemical compound and disease context of Fabry Disease

• Histamine flare in Fabry's disease [10].
• Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium [11].
• Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease [12].
• Examination of renal tubular cells in urine using the fluorescein antibody technic described here affords a noninvasive means of diagnosing and following the effect of therapy in patients with Fabry's disease [13].
• A mammalian-like sugar moiety was created in glycoprotein by Saccharomyces cerevisiae in combination with bacterial alpha-mannosidase to produce a more economic enzyme replacement therapy for patients with Fabry disease [14].

Biological context of Fabry Disease

• Gene diagnosis of the mother and a female cousin was successfully achieved by polymerase chain reaction amplification of genomic DNA; the former as a Fabry disease heterozygote and the latter as a normal homozygote [15].
• These studies reveal a potent vascular prothrombotic phenotype in Gla-deficient mice and suggest that antithrombotic therapies as well as therapies designed to reduce the vascular accumulation of Gb3 may have beneficial effects on thrombotic complications in patients with Fabry disease [16].
• Retroviral coexpression of a multidrug resistance gene (MDR1) and human alpha-galactosidase A for gene therapy of Fabry disease [17].
• Effect of vitamin E and ticlopidine on platelet aggregation in Fabry's disease [18].
• This suggests that many missense mutations in the alpha-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose [19].

Anatomical context of Fabry Disease

• These studies demonstrate the potential of using a huCD25-based preselection strategy to enhance the clinical utility of ex vivo hematopoietic stem/progenitor cell gene therapy of Fabry disease and other disorders [20].
• The effect of galactose on alpha-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts [19].
• Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels [21].
• This could have been secondary to Anderson-Fabry disease aggravated by a minor infection, an idiosyncratic reaction to Dilantin, or the lymph node equivalent of the granulomatous response that later affected the gingiva [22].
• Senescent erythrocytes are considered a major source of the ceramide trihexoside which accumulates in Fabry disease patients [23].

Gene context of Fabry Disease

• In order to investigate the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk [24].
• The frequencies of eNOS 4b/a polymorphisms are also significantly different in Fabry's disease when compared to controls [25].
• Fabry disease: 20 novel GLA mutations in 35 families [26].
• Hypertrophic obstructive cardiomyopathy due to Fabry's disease [27].
• Letter: Occurrence of celiac sprue in a patient with Fabry's disease [28].

Analytical, diagnostic and therapeutic context of Fabry Disease

• We previously have demonstrated long-term alpha-gal A enzyme correction and lipid reduction mediated by therapeutic ex vivo transduction and transplantation of hematopoietic cells in a mouse model of Fabry disease [20].
• Thus, DNA analysis can be used for presymptomatic and prenatal diagnosis in most portions of the Nova Scotia kindred affected with Fabry disease [29].
• Recent clinical trials have demonstrated that enzyme replacement therapy with alpha-galactosidase A (alpha-Gal A) constitutes a major clinical advance in the treatment of patients with Fabry disease [30].
• Successful pregnancy outcome in a patient with Fabry disease receiving enzyme replacement therapy with agalsidase alfa [31].
• Thus, a 47-year-old male with Fabry's disease was examined with Cochet-Bonnet's esthesiometer, photokeratometry, ultrasonography, electropupillography, electroretinography, electro-oculography and fluorescein fundus angiography [32].

References