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)

A male patient with fucosidosis exhibited the following characteristics: 1. Early onset and rapid progression of neurological symptoms. 2.Skin changes compatible with angiokeratoma corporis diffusum. 3. Complete or nearly complete deficiency of alpha-fucosidase. 4. Survival to adult age (20 years). The deficiency of alpha-fucosidase was demonstrated in liver, tears, urine, sediment, and cultured fibroblasts. We conclude that severe deficiency or complete absence of alpha-fucosidase does not by itself preclude survival to adult age.
Eur J Pediatr 1980 Dec
PMID:Fucosidosis: severe phenotype with survival to adult age. 677

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.
Am J Kidney Dis 1995 Dec
PMID:A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody. 750 71

Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A (alpha-Gal A) gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder-variant Fabry phenotypes, and for precise carrier detection in Fabry families, the alpha-Gal A transcripts or genomic sequences from unrelated Fabry hemizygotes were analyzed. In patients with the classical phenotype, 18 new mutations were identified: N34S, C56G, W162R, R227Q, R227X, D264V, D266V, S297F, D313Y, G328A, W340X, E398X, IVS2+2, IVS5 delta-2,3, 773 delta 2, 954 delta 5, 1016 delta 11, and 1123 delta 53. Unrelated asymptomatic or mildly affected patients with symptoms confined to the heart had a missense mutation, N215S, that expressed residual enzymatic activity. Related, moderately affected patients with late-onset cardiac and pulmonary manifestations had a small deletion, 1208 delta 3, that predicted the in-frame deletion of arginine 404 near the terminus of the 429 residue enzyme polypeptide. In addition, five small gene rearrangements involving exonic sequences were identified in unrelated classically affected patients. Two small deletions and one small duplication had short direct repeats at their respective breakpoint junctions and presumably resulted from slipped mispairing. A deletion occurred at a potential polymerase alpha arrest site, while the breakpoints of another deletion occurred at an inverted tetranucleotide repeat. Screening of unrelated Fabry patients with allele-specific oligonucleotides for seven mutations revealed that these were private, with the notable exception of N215S, R227Q, and R227X, which were each found in several unrelated families from different ethnic backgrounds. The CpG dinucleotide at codon 227 was the most common site of mutation, having been altered in 5% of the 148 unrelated Fabry alleles. These studies revealed that most alpha-Gal A lesions were private, that codon 227 was a mutational hot spot, and that certain mutations predicted a milder disease phenotype.
Am J Hum Genet 1993 Dec
PMID:Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. 750 5

The expression product of a mutant alpha-galactosidase gene, Q279E (279Gln-->Glu), found in an atypical variant (cardiac form) of Fabry disease, was purified and characterized. It had kinetic properties similar to those of normal alpha-galactosidase, but was markedly thermolabile at neutral pH. Galactose and melibiose at high concentrations stabilized the mutant enzyme in vitro. Its catalytic activity was 15% of that for the normal enzyme, when it was expressed in COS-1 cells at 37 degrees C. The activity increased at 30 degrees C or in the presence of galactose at 37 degrees C. An increase was also observed in lymphoblasts from a patient with this mutation in the presence of galactose or melibiose. We conclude that this mutant protein is posttranslationally inactivated under the neutral conditions in the cells. The possibility of a new therapeutic approach is suggested.
Biochem Biophys Res Commun 1993 Dec 30
PMID:Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease. 790 61

An immunofluorometric method was developed for the semiquantitative determination of trihexosylceramide in cultured fibroblasts from Fabry disease patients, using a laser scanning confocal imaging system. The accumulated glycolipid was detected as granular inclusions in the cells. Heterozygote identification was achieved both by counting of immunoreactive cells and by measuring the relative fluorescence intensity with a digital imaging system.
Clin Genet 1993 Dec
PMID:Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy. 813 1

alpha-Galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22; alpha GalA) is a lysosomal enzyme that hydrolyses the alpha-D-galactosyl residues from glycosphingolipids. Fabry disease, an inhibited X-linked recessive human metabolic disorder, results from a mutation in the alpha GalA gene at Xq22. As a prerequisite for generating a mouse model of Fabry disease by gene targeting, we have isolated and characterized the mouse alpha GalA gene and cDNA. A cloned mouse alpha GalA cDNA encoded a putative precursor protein of 419 amino acids (aa), including a 31-aa signal peptide (SP). The deduced aa sequence showed high homology (79%) with the human alpha GalA protein. Nucleotide sequence analysis of genomic clones revealed that the overall structure and organization of the gene was very similar to that of human alpha GalA. All exon-intron splice junctions conformed to the GT/AG consensus sequence. Comparison of genomic and cDNA sequences revealed the occurrence of two putative polyadenylation signals whose alternative use results in the two mouse alpha GalA transcripts of 1.4 and 3.6 kb. The 5'-flanking region of mouse alpha GalA had no typical TATA box. Several putative promoter-associated elements including Sp1, AP1 and a potential cAMP-responsive element (CRE) were identified. Northern blot analysis revealed the widespread tissue distribution of mouse alpha GalA transcripts. Lower expression levels, however, were observed in some tissues, implying tissue-specific differences in alpha GalA promoter function.
Gene 1995 Dec 12
PMID:Structural organization and expression of the mouse gene encoding alpha-galactosidase A. 854 75

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.
Nihon Rinsho 1995 Dec
PMID:[Fabry disease (alpha-galactosidase deficiency)]. 857 42

Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49). Two German children were first reported in 1987 and other two Dutch children were recently reported in 1993. These children were very similar clinically and characterized by maked neuroaxonal dystrophy of an infantile onset. This disease (type 1) was named Schindler disease. On the other hand, an adult patient with profuse angiokeratoma corporis diffusum but minimum involvement in nervous system was reported in 1987 from Japan. This disease (type 2) was named Kanzaki disease (Mckusick catalog No. 104170). Molecular analyses of these diseases revealed one each point mutation in the encoding gene. Clinical, ultrastructural and molecular studies of these disease were described.
Nihon Rinsho 1995 Dec
PMID:[Schindler disease/Kanzaki disease]. 857 46

There are 6 well known lysosomal storage diseases which produce angiokeratoma corporis diffusum clinically. The clinical, histological, ultrastructural and biochemical characteristics are discussed. The best known angiokeratoma will be observed in patients with Fabry disease. Angiokeratoma in Fabry disease, however, may be much fewer than thought previously. Fucosidosis and galactosialidosis are next well known diseases to produce angiokeratoma. Approximately 50% of patients with these diseases have angiokeratoma. Recently reported Kanzaki disease, beta-mannosidosis and aspartylglucosaminuria will show angiokeratoma more or less extensively. Ultrastructurally Fabry disease only produce electron dense deposits in lysosomes and others electron lucent. These are summarized in Table 1 in the text.
Nihon Rinsho 1995 Dec
PMID:[Lysosomal storage diseases with angiokeratoma corporis diffusum]. 857 59

The history and bases of enzyme replacement therapy are briefly reviewed. The enzyme replacement therapy for Gaucher disease type 1, which has been developed for clinical use and is about to be introduced in our country, was described somewhat in detail under the items of the modification of human placental glucocerebrosidase into the macrophage-terminated enzyme, its clinical usage, effects and their evaluations, adverse effects, and new attempts of its application for Gaucher disease types II and III, now being under clinical trials. Also touched are developments of other enzymes for such lysosomal diseases as Fabry disease, Pompe disease, Hurler syndrome, Hunter disease, and Sly disease.
Nihon Rinsho 1995 Dec
PMID:[Enzyme replacement therapy of patients with lysosomal storage disease]. 857 62


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