Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For comparative studies we have used the somatic cell hybridization approach to regionally map genes on the mouse X chromosome. Fibroblasts from a mouse with the balanced reciprocal translocation T(XD;16B5)16H were fused with a Chinese hamster cell line (V79/380-6) deficient in activity of the enzyme hypoxanthine phosphoribosyltransferase (HPRT). Interpecific cell hybrids were initially selected for retention of the mouse translocation chromosome carrying the Hprt gene. Subsequently, hybrid clones were counterselected to force segregation of this chromosome. Selected and counterselected hybrid clones were analyzed for their chromosome content by trypsin/Giemsa banding and for expression of the mouse forms of the X-linked enzymes HPRT and alpha-galactosidase (GALA) by isoelectric focusing. The results indicate that the breakpoint on the mouse X chromosome (in band XD) has separated the genes for HPRT (Hprt) and for GALA (Ags). Hprt is proximal to the breakpoint in region Xcen-XD and Ags is distal in region XD-Xter. The gene order in the mouse (centromere-Hprt-Ags) is therefore inverted when compared to the order of the homologous loci on the long arm of the human X (centromere-GALA-HPRT).
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PMID:Comparative gene mapping: order of loci on the X chromosome is different in mice and humans. 625 72

In Fabry disease, as in other X-linked traits, identification of all heterozygotes is difficult. Reduced plasma alpha-galactosidase activities will correctly identify 60-70% of the carriers. The identification rate improves when an alpha/beta-galactosidase activity enzyme ratio is used. We measured alpha-galactosidase activity in reference to several other enzyme activities, beta-galactosidase, beta-hexosaminidase, and alpha-fucosidase in plasma and leukocytes from 22 suspected and 9 obligate carriers from 4 kindreds of Fabry disease patients. Utilizing such ratios or various combinations of ratios in plasma we have correctly identified the carrier state in 91% of heterozygotes. Leukocyte alpha/beta-galactosidase identified one more female than leukocyte alpha-galactosidase activities alone. We recommend the use of such multiple biochemical tests to identify carriers of Fabry disease.
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PMID:Heterozygote detection in Fabry disease utilizing multiple enzyme activities. 627 91

Apparent deficiency of alpha-galactosidase A was observed in a 51-year-old, clinically healthy male, with no clinical symptoms of Fabry disease, and without excess urinary excretion of ceramide trihexoside. The deficiency, which was similar to that found in Fabry disease patients, could be demonstrated using both synthetic and natural substrates. This pseudodeficiency was transmitted in his family by classical X-linked inheritance. His wife showed enzyme activity in the normal range, two daughters were heterozygotes for this mutation as demonstrated by hair root assay, and three sons showed normal alpha-galactosidase activity. Kinetic studies in cultured skin fibroblasts indicated a five-fold increase in the apparent Km and a greater heat stability of the residual alpha-galactosidase activity when compared to controls. These data indicate that the residual enzyme activity in this mutation behaves similarly to that observed in Fabry disease patients but does not cause any clinical abnormalities.
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PMID:Pseudodeficiency of alpha-galactosidase A. 627 39

The first part of this review deals with the new biochemical and genetical data concerning alpha-galactosidase and alpha-N-acetylgalactosaminidase. Molecular forms of these both enzymes can be classified into two groups following their physical, enzymatic and genetical properties: - the 3 forms of the alpha-galactosidase A group differ by the number of sialyl residues and their isoelectric point. All the forms of this group are heat-labile, hydrolyse only alpha-galactosides and proceed from the same alpha-GalA, X-linked gene. - alpha-galactosidase B is an alpha-N-acetylgalactosaminidase with broad substrate specificity, in vitro, is heat-stable and proceed from the alpha- GalB or alpha- NAGA gene of the chromosome 22. Structural and enzymatic data concerning these enzymes and their functions in the catabolism of glycosphingolipids and glycoproteins are reviewed. The second part deals with the pathophysiology of Fabry disease. The more prominent genetical and biochemical data and their diagnostic uses are reported: isozymic determination, cell cloning, quantitative determination of accumulated glycolipids. At last, were pointed the new developments of the research on Fabry disease: cultured cells as experimental model (fibroblasts, lymphoid cell lines) and therapeutic attempts.
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PMID:[Alpha-galactosidases and alpha-N-acetylgalactosaminidase. Biochemical bases of Fabry's disease]. 632 22

A 69,XXX female liveborn triploid survived 45 days. The phenotype was consistent with the average clinical picture of liveborn triploids. Autopsy revealed slight atrophy of cerebral cortex and corpus callosum and severe adrenal hypoplasia. Chromosome polymorphisms indicated that the origin of this triploid was dispermy. Replication studies of the X chromosome performed on lymphocytes and fibroblasts showed that the majority of cells had two late replicating X chromosomes. X chromosome inactivation in spontaneous abortuses and liveborn triploids is discussed. Nine enzymes encoded by autosomal genes were tested, five had normal, three increased, and one reduced levels of activity. The reduced activity of alpha-galactosidase, an X-linked enzyme, is in agreement with cytogenetic findings and demonstrated a gene dosage effect.
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PMID:A liveborn 69,XXX triploid. Origin, X chromosome activity and gene dosage. 633 97

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase. Patients with classic Fabry disease of early onset show diverse clinical manifestations caused by generalized vasculopathy. Recent clinical and enzymatic examinations have revealed another form of this disease; progressive cardiomyopathy of late onset without other systemic signs or symptoms. Efforts were directed to identify the specific mutations in the alpha-galactosidase gene and to clarify the phenotype/genotype correlations. A variety of mutations, including deletions, nonsense mutations, splicing mutations and amino acid substitutions caused the classic form of Fabry manifestations, which resulted in the complete deficiency of alpha-galactosidase activity. Single base substitutions were detected in the upstream region of alpha-galactosidase gene exon 6, which resulted in residual enzyme activity. The degree of the expressed residual enzyme activity might determine the clinical phenotypes. Heterozygotes were successfully identified by gene analysis and immunofluorescence imaging diagnosis using confocal laser scanning microscopy.
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PMID:[Molecular genetics of inherited metabolic diseases--its application to the investigation of pathogenesis and the diagnosis of Fabry disease]. 791 43

Fabry's disease is a rare, inherited, X-linked metabolic storage disease with ceramide hexoside due to alpha-galactosidase A deficiency. Patients with typical Fabry's disease usually present with several clinical manifestations of corneal dystrophy, neurologic abnormalities, cardiovascular disease, heavy proteinuria, and characteristic cutaneous angiokeratoma. However, atypical Fabry's disease with oligosymptomatic phenotype presents with symptoms restricted solely to cardiocytes or kidney and might be diagnosed by chance during a routine endomyocardial or renal biopsy examination. In this article, we report a case of Fabry's disease incidentally diagnosed in a 34-year-old man who presented with intermittent trace or 1(+) proteinuria only. This patient had no history of renal disease in any other family member. A renal biopsy to evaluate trace proteinuria revealed histologic and ultrastructural findings compatible with Fabry's disease. Subsequent to the renal biopsy, a skin biopsy on a few initially unrecognized, scattered, dark-pinkish scrotal papules showed typical angiokeratoma. A biochemical enzymatic assay of alpha-galactosidase in urine and plasma revealed a markedly decreased enzyme level in the hemizygous range.
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PMID:Atypical Fabry's disease. An oligosymptomatic variant. 855 52

Fabry disease is an X-linked glycosphingolipid storage disorder resulting from a deficiency of lysosomal alpha-galactosidase (alpha-Gal; EC 3.2.1.22). Classical form patients, with clinical manifestations of generalized angiopathy of early onset, usually show no detectable alpha-Gal activity. There are also atypical form patients with residual alpha-Gal activity and late onset cardiomyopathy without other systemic manifestations. We identified a number of alpha-Gal gene mutations including partial deletions and point mutations. They were heterogeneous and more than half of them were missense mutations. Various missense mutants were expressed in COS-1 cells. Two groups have been identified; one expressing a mutant enzyme without catalytic activity, and the other expressing a catalytically active but unstable mutant enzyme. The latter was restored in patient cells by the addition of substrate analogues. The molecular genetic and biochemical analysis for Fabry disease will provide us with significant informations on the pathogenesis and the possibility of the therapeutic approach for this disease.
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PMID:[Fabry disease (alpha-galactosidase deficiency)]. 857 42

Fabry's disease, X-linked alpha-galactosidase deficiency, features a variety of autonomic abnormalities including anhidrosis. In this study, we measured the skin sympathetic nerve activity (SSNA), skin potential and sweat rate in a symptomatic female carrier to investigate the underlying pathophysiology of anhidrosis. The basal activity and responsiveness of SSNA were both fairly well preserved, although slightly reduced compared with the control levels. However, sweating was completely absent, despite the normal skin potential change in response to SSNA bursts. These results suggest that anhidrosis in Fabry's disease is a result of sweat gland dysfunction as well as abnormal SSNA.
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PMID:Possible mechanism of anhidrosis in a symptomatic female carrier of Fabry's disease: an assessment by skin sympathetic nerve activity and sympathetic skin response. 872 95

Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation Of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (>10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity).
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PMID:Correction in trans for Fabry disease: expression, secretion and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector. 875 77


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