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)

Polyethylene glycol-1000 (PEG-1000) induced fusion of HPRT (E.C. 2.4.2.8) deficient Chinese hamster cells with alpha-galactosidase A (E.C. 2.3.1.22) deficient cells from a patient with Fabry's disease yielded hybrids which contained both human and hamster HPRT, G6PD (E.C. 1.1.1.49), and APRT (E.C. 2.4.2.7) and Chinese hamster alpha-galactosidase B. Thus PEG-1000 mediated somatic cell fusion led to reexpression of Chinese hamster HPRT. It did not restore the expression of human alpha-galactosidase. Since PEG-1000 treatment of HPRT- Chinese hamster cells in the absence of human cells yielded no HPRT+ cells, it is concluded that the element responsible for the restoration of rodent HPRT was contributed by the human cells and not by the agent employed to promote fusion.
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PMID:Reexpression of HPRT activity following cell fusion with polyethylene glycol. 20 82

Biochemical investigations on blood-plasma and serum as well as well as electron microscopic investigations on skin lesions biopsy specimens were carried out in one case of morbus Fabry 35 years of age distinctly showing cardio-renal symptoms. The diagnosis of Fabry disease was made when the patient was hospitalized for treatment of a chronic glomerulonephritis. The patients' serum alpha-galactosidase activity was reported to be 10 to 13% of normal controls, whereas the values of trihexosyl-ceramids for blood-plasma and serum were increased. Electron microscopic studies revealed that the endothelial cells and pericytes of the cutaneous vessels as well as the fibroblasts contain numerous liposome-like cytoplasmic inclusions of different size showing an internal lamellar structure with exact periodizity of 65 A. These inclusion are not surrounded by a membrane structure, however, it is possible that the arise from defect lysosomes which accumulate trihexosyl-ceramids owing to insufficient of alpha-galactosidase activity.
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PMID:[Fabry disease: clinical, biochemical and electron microscopical studies (author's transl)]. 22 Jan 5

1. Normal human leukocytes present three molecular forms of alpha-galactosidase (EC 3.2.1.22) separated using electrofocusing: a new major form IV (pI 4.0) characteristic of leukocytes and two forms that exist in other tissues, form I (pI 4.5) and form II (pI 4.0). 2. Normal human leukocytes present only one molecular form (pI 4.5) of N-acetyl-alpha-galactosaminidase (EC 3.2.1.49) corresponding to alpha-galactosidase form II. 3. In leukocytes from patients with Fabry disease, the electrofocusing shows that the alpha-galactosidase lacking corresponds to forms I and IV, while the residual activity corresponds to form II (or N-acetyl-alpha-galactosaminidase).
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PMID:[Molecular forms of human leukocytic alpha-galactosidase and N-acetyl-alpha-galactosaminidase]. 22 74

The relationship between biochemical parameters and clinical symptoms in angiokeratoma corporis diffusum universale (Anderson-Fabry's disease) has been studied in an extensive English family. The biochemical parameters measured were alpha-galactosidase activity in urine and in single hair roots and the urinary glycosphingolipid excretion per 24 h. The clinical symptoms evaluated included the occurrence of pain, the prevalence of skin lesions, an abnormal ECG, cornea verticillata and other features. Nine male patients and 13 female carriers were studied. No correlation between biochemical parameters and the severity of the clinical symptoms could be found either in the hemizygotes or in the heterozygotes. The urinary alpha-galactosidase activity in all the heterozygotes lay within the normal range. All the obligate heterozygotes (mothers and daughters of hemizygotes) could be detected by analysis of hair roots. Additional heterozygotes were recognized on the basis of clinical symptoms and hair root analysis.
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PMID:Relationship between biochemical and clinical features in an English Anderson-Fabry family. 22 29

A pilot trial of enzyme replacement with splenic and plasma alpha-galactosidase A (alpha-D-galactosidase; alpha-D-galactoside galactohydrolase, EC 3.2.1.22) isozymes was undertaken in two brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Six unentrapped doses (2000 units/kg) of each isozyme were administered intravenously to the respective recipients during a 117-day period. The circulating half-life of the splenic isozyme was about 10 min, whereas that for the plasma isozyme was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either isozyme after successive administrations. After each dose of the splenic isozyme, the concentration of the accumulated circulating substrate, trihexosylceramide (globotriaosylceramide), decreased maximally (approximately 50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma isozyme decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations gradually returned to preinfusion values by 36-72 hr.
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PMID:Enzyme therapy in Fabry disease: differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galactosidase A isozymes. 22 84

In a 16-member black kindred with Fabry's disease, four hemizygous males had plasma alpha-galactosidase levels less than 6% and seven heterozygous females had plasma alpha-galactosidase levels between 10% and 50% of normal. A 16-year-old index male had hypertension with left ventricular hypertrophy, abnormal renal function, tortuous retinal veins, "myelin" inclusions in bone marrow macrophages, and intraepithelial inclusion bodies in the kidney. Scrotal angiectasia developed a year after diagnosis. The three other affected males had left ventricular hypertrophy and retinal vein tortuosity. Of the seven carrier females, five had frequent headaches, four had retinal vessel changes, three had proteinuria with normal renal function, and two had bundle-branch blocks on ECGs. There was no deuteranomalopia in this family, although the inheritance pattern of the Fabry gene is X-linked recessive.
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PMID:Fabry's disease in a black kindred. 22 50

A rapid and simple method is described for the identification of the carrier state in angiokeratoma corporis diffusum. The alpha-galactosidase (alpha-D-galactoside galactohydrolase, E.C.3.2.1.22) activities in individual hair roots are measured and compared with those of N-acetyl-beta-hexosaminidase (E.C.3.2.1.30), another lysosomal enzyme that is not affected. The cellular mosaicism typical of females heterozygous for X-linked disorders is revealed by the presence of normal, affected and partially affected hair roots. Normal individuals show no affected roots, while males hemizygous for the trait have no hair roots with enzyme activities in the normal range.
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PMID:Anderson-Fabry disease: rapid detection of carriers by hair bulb analysis. 22 42

The enzymatic diagnosis of hemizygotes with Fabry disease and heterozygous carriers was accomplished by the fluorometric determination of alpha-galactosidase activities in tears. Two components of total alpha-galactosidase activity were differentiated by their relative thermostabilities and by chromatography on DEAE-cellulose. The major component, alpha-galactosidase A, was thermolabile and represented approximately 90% of total activity; the remaining activity was thermostable, eluted at a slightly higher salt concentration and was designated alpha-galactosidase B. A single, symmetric pH optimum was observed for total alpha-galactosidase activities from heterozygotes and normal individuals, whereas the total activity from hemizgotes, which was about 10% of that in normal controls, had a broad pH profile, identical to those for alpha-galactosidase B activities from all individuals studied. The apparent Km values for total activities were 3.2, 4.0, and greater than 13 mM for normal individuals, heterozygotes, and hemizygotes, respectively. In contrast, apparent Km values for alpha-galactosidase B activities were greater than 13 mM for all individuals, further suggesteng that the residual activity in hemizygotes with Fabry disease represented the alpha-galactosidase B component. of the potential inhibitors studied, alpha-D-melibiose was found to competitively inhibit total alpha-galactosidase activity (Ki approximately 10 mM). These studies demonstrate that tears provide an easily obtainable source of freshly secreted enzyme for the diagnosis of hemizygotes and heterozygotes with Fabry disease and suggest that tears may be useful for the diagnosis of other inborn errors of metabolism.
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PMID:Fabry disease: diagnosis by alpha-galactosidase activities in tears. 24 13

The alpha-galactosidases in normal man-Chinese hamster somatic cell hybrids were investigation with antibodies specific for human alpha-galactosidase A and antibodies specific for Chinese hamster alpha-galactosidase. It was found that an isoenzyme in hybrid cells, which has an electrophoretic mobility between that of human alpha-galactosidase A and Chinese hamster alpha-galactosidase, contains immunologic determinants of both human and Chinese hamster origin, suggesting that it is a heteropolymeric molecule. Moreover, the locus for human alpha-galactosidase, which was found to be X-linked, is the locus coding for alpha-galactosidase A. Hybrids isolated after fusion of Chinese hamster cells with cells of a patient with Fabry's disease did not express human alpha-galactosidase A or the heteropolymeric molecule even in the presence of the active human X chromosome, indicating that the deficiency of alpha-galactosidase A in Fabry's disease is probably due to a mutation in a structural gene resulting in the inability to form immunologically detectable and functionally active molecules of alpha-galactosidase A.
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PMID:Characterization of alpha-galactosidase isoenzymes in normal and Fabry human-Chinese Hamster somatic cell hybrids. 40 32

Heterozygote detection for angiokeratoma corporis diffusum (Anderson-Fabry disease, ACD), an X-linked disorder of glycosphingolipid metabolism was examined using alpha-galactosidase activity, an alpha-galactosidase/beta-galactosidase activity ratios (alpha/beta ratio) in leucocytes, plasma, and hair follicles; For leucocytes, 22 obligate heterozygotes, 25 suspected heterozygotes, and 47 control subjects were studied, while for plasma, the groups were 17 obligate heterozygotes and 35 controls. The alpha/beta ratio in plasma and leucocytes was clearly a better discriminator between obligate heterozygotes and controls than alpha-galactosidase activity alone, but still failed to detect 3 obligates with leucocytes and 2 with plasma. Discrimination was not improved by joint use of plasma and leucocyte alpha/beta ratios, but was improved by measurement of hair-follicle alpha/beta ratios. The interdecile range of log (alpha-galactosidase/beta-galactosidase activity) in 20 hair follicles from each of 4 obligate and 7 suspected heterozygotes was clearly different from 11 control subjects. Accordingly, for rapid screening for carriers of ACD, we recommend use of leucocyte or plasma alpha/beta ratios which should detect greater than 85% of heterozygotes. When results are equivocal, and ancillary information suggests heterozygous status, the more time-consuming measurement of hair-follicle alpha/beta ratios is a useful additional test.
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PMID:Heterozygote detection in angiokeratoma corporis diffusum (Anderson-Fabry disease). Studies on plasma, leucocytes, and hair follicles. 40 11


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