Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three men with Fabry's disease (angiokeratoma corporis diffusum universal ) are described. In the first patient, atrial fibrillation appeared, and a permanent cardiac pacemaker (VVI) was implanted. Sick sinus syndrome with complete atrioventricular block was occurred on the second patient. Transvenous pacemaker (DDD) implantation was performed for him. The last patient was younger brother of the second patient. He demonstrated complete atrio-ventricular block, so cardiac pace maker (VAT) was implanted. They showed a low value of granulocyte's alpha-galactosidase activity. During 1 to 4 year follow up period, they showed no trouble about pacemaking. Fabry's disease is an disorder of glycosphingolipid metabolism. This disorder is characterized by the accumulation of trihexosyl ceramide in many sites. Cardiac involvement and abnormal electrocardiographic manifestations are common in this disorder. Permanent cardiac pacemaker is necessary for severe bradycardia caused by this disorder.
 ...
PMID:[Transvenous permanent pacemaker implantation for Fabry's disease. 3 cases report]. 250 43

Fabry disease, an X-linked recessive disorder of glycosphingolipid catabolism, results from the deficient activity of the lysosomal hydrolase, alpha-galactosidase. 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. Five partial gene deletions were detected ranging in size from 0.4 to greater than 5.5 kb. Four of these deletions had breakpoints in intron 2, a region in the gene containing multiple Alu repeat sequences. A sixth genomic rearrangement was identified in which a region of about 8 kb, containing exons 2 through 6, was duplicated by a homologous, but unequal crossover event. The Msp I site obliteration, which mapped to exon 7, was detected in an affected hemizygote who had residual enzyme activity. Genomic amplification by the polymerase chain reaction and sequencing revealed that the obliteration resulted from a C to T transition at nucleotide 1066 in the coding sequence. This point mutation, the first identified in Fabry disease, resulted in an arginine356 to tryptophan356 substitution which altered the enzyme's kinetic and stability properties. The detection of these abnormalities provided for the precise identification of Fabry heterozygotes, thereby permitting molecular pedigree analysis in these families which revealed paternity exclusions and the first documented new mutations in this disease.
 ...
PMID:Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene. 253 98

We report a rare heterozygous status for Fabry's gene with severe kidney involvement and normal alpha-galactosidase A activity, together with the intrafamilial variations in the clinical expression of the disease. The random X inactivation hypothesis seems to explain such a variable expression of the alpha-galactosidase gene in our cases.
 ...
PMID:[Fabry's disease: kidney insufficiency in heterozygous patient]. 256 53

Human alpha-galactosidase A (alpha-D-galactoside galactohydrolase; EC 3.2.1.22) is a lysosomal hydrolase encoded by a gene localized to the chromosomal region Xq22. The deficient activity of this enzyme results in Fabry disease, an X chromosome-linked recessive disorder that leads to premature death in affected males. For studies of the structure and function of alpha-galactosidase A and for characterization of the genetic lesions in families with Fabry disease, the full-length cDNA was isolated, sequenced, and used to screen human genomic libraries. The 1393-base-pair full-length cDNA had a 60-nucleotide 5' untranslated region and encoded a precursor peptide of 429 amino acids including a signal peptide of 31 residues. Three overlapping lambda clones spanning 32 kilobases were identified that contained the entire approximately equal to 12-kilobase chromosomal gene as well as approximately equal to 9 and approximately equal to 11 kilobases of 5' and 3' flanking sequence, respectively. The gene had seven exons. The genomic exonic and full-length cDNA sequences were identical. All intron-exon splice junctions conformed to the GT/AT consensus sequence. The 5' flanking region of this lysosomal housekeeping gene contained Sp1 and CCAAT box promoter elements as well as sequences corresponding to the activator protein 1 (AP1), octanucleotide ("OCTA"), and "core" enhancer elements. There was an upstream "HTF" island (Hpa II tiny fragments) followed by four direct repeats of the "chorion box" enhancer. The unique lack of a 3' untranslated sequence in the alpha-galactosidase A cDNA was confirmed by sequencing additional cDNA clones and the genomic 3' region.
 ...
PMID:Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region. 283 63

Fabry's disease is characterized by an inherited X-linked disorder of glycosphingolipid catabolism, and heterozygous women affected with this disease who show overt symptoms including cardiac manifestations have rarely been reported. To elucidate the features of myocardial involvement in female patients, noninvasive techniques including exercise stress thallium-201 myocardial scintigraphy were performed. Three female patients, Cases 1-3, 26, 29 and 50 years of age, were documented low leucocytic alpha-galactosidase activities of less than 48% of normal (67.92-16.2 nmol/mg protein/h). They were examined using ECG, two-dimensional echocardiography (2-D Echo), Holter ECG, treadmill test and stress scintigraphy. On the ECG, negative T waves were shown in leads III and aVF in Cases 1 and 2. Left ventricular high voltage, giant negative T waves and short PR intervals were seen in Case 3. The 2-D Echo revealed neither valvular change nor left ventricular hypertrophy. On the Holter ECG, monofocal ventricular premature beats were occasionally observed in Cases 1 and 3. The treadmill test showed positive ST changes only in Case 2. On the exercise stress scintigraphy, uptake of thallium-201 was enhanced in the apex of the heart in Cases 2 and 3. Low uptake areas of thallium-201 were observed in Case 3. The ventricular angiogram revealed slight hypertrophy of the wall of the apical portion. In endocardial biopsies from the right ventricle, myelinoid lamellar inclusions were demonstrated in myocardial cells electron microscopically. Increased uptake of thallium-201 in the apex was noted in two of the three patients, but no apical thickening was noticed in any of the three cases by 2-D Echo. From the result of the biopsy of Case 3, the increased apical uptake of thallium-201 seems to reflect thickening caused by the deposition of glycosphingolipid. It was concluded that myocardial involvement in female Fabry's disease may occur early in the third decade and that the lesions could be detected with high sensitivity by thallium-201 myocardial scintigraphy.
 ...
PMID:[Myocardial involvement in female Fabry's disease: evaluation by thallium-201 myocardial scintigraphy]. 297 3

Fabry's disease (angiokeratoma corporis diffusum) is an X-linked recessive inherited metabolic defect due to the lack of the enzyme alpha-galactosidase A. We reviewed the Argentine literature on the subject, the main features of the disease and its differential diagnosis. Two patients aged ten and fifteen are described showing the characteristic clinical picture of the disease since ages four and nine respectively. Skin and conjunctival ultrastructural studies showed intracytoplasmatic granules with a lamellar appearance in the endothelial cells, pericytes and fibroblasts. Plasma levels of alpha-galactosidase activity were sharply decreased in the two patients studied and partially decreased in their heterozygous mothers.
 ...
PMID:[Angiokeratoma corporis diffusum (Fabry's disease). Update. Apropos of 2 cases]. 299 36

The skin of a patient with Fabry's diffuse angiokeratoma accompanied by a severe decrease of leucocyte alpha-galactosidase (0,7-1,2 nmol/mg protein/h) was studied by a method of semithin and ultrathin sections. Cytoplasmic inclusions having lamellar structure in the form of alternating electron-dense and light strips with a period about 6 nm were found in the endotheliocytes of dilated vessels, lymphoid cells, neutrophil leucocytes, axons and leucocytes of nerve trunks. The presence of these specific inclusions together with the decrease of leucocytic alpha-galactosidase allows the differential diagnosis with other types of angiokeratomas and some skin angiomas.
 ...
PMID:[Ultrastructural changes in the skin of patients with Fabry's angiokeratoma]. 299 71

Fabry disease is an X-linked inborn error of metabolism resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A; alpha-D-galactoside galactohydrolase, EC 3.2.1.22). To investigate the structure, organization, and expression of alpha-Gal A, as well as the nature of mutations in Fabry disease, a clone encoding human alpha-Gal A was isolated from a lambda gt11 human liver cDNA expression library. To facilitate screening, an improved affinity purification procedure was used to obtain sufficient homogeneous enzyme for production of monospecific antibodies and for amino-terminal and peptide microsequencing. On the basis of an amino-terminal sequence of 24 residues, two sets of oligonucleotide mixtures were synthesized corresponding to adjacent, but not overlapping, amino acid sequences. In addition, an oligonucleotide mixture was synthesized based on a sequence derived from an alpha-Gal A internal tryptic peptide isolated by reversed-phase HPLC. Four positive clones were initially identified by antibody screening of 1.4 X 10(7) plaques. Of these, only one clone (designated lambda AG18) demonstrated both antibody binding specificity by competition studies using homogeneous enzyme and specific hybridization to synthetic oligonucleotide mixtures corresponding to amino-terminal and internal amino acid sequences. Nucleotide sequencing of the 5' end of the 1250-base-pair EcoRI insert of clone lambda AG18 revealed an exact correspondence between the predicted and known amino-terminal amino acid sequence. The insert of clone lambda AG18 appears to contain the full-length coding region of the processed, enzymatically active alpha-Gal A, as well as sequences coding for five amino acids of the amino-terminal propeptide, which is posttranslationally cleaved during enzyme maturation.
 ...
PMID:Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A. 299 89

An endothelial cell line has been established from the umbilical vein obtained after abortion of a male fetus suffering from Fabry disease. This X-linked inborn error of glycosphingolipid catabolism results from deficiency of the lysosomal hydrolase alpha-galactosidase A. The clinical manifestations of the disease are mainly caused by glycosphingolipid depositions in the endothelium of all vessels. The hemizygous cell line and eight endothelial cell lines originating from the umbilical cords of normal newborns were grown for more than 10 passages. They had a short generation time that allowed us to get sufficient cells for qualitative and quantitative investigations of alpha-galactosidase. The enzyme in normal endothelial cells had a similar thermostability and isoelectric focusing pattern as that in fibroblasts, but the activity was essentially higher in endothelial cells. The hemizygous endothelial cells were deficient in alpha-galactosidase A. It is concluded that endothelial cell lines are an important alternative to fibroblasts for in vitro studies of the lysosomal storage diseases.
 ...
PMID:Lysosomal alpha-galactosidase in endothelial cell cultures established from a Fabry hemizygous and normal umbilical veins. 300 54

Six pregnancies of three carriers for X-linked Fabry's disease, were monitored by chromosome and enzyme analysis. Two affected male fetuses were detected by the demonstration of alpha-galactosidase deficiency in amniotic fluid cells and chorionic villi respectively. The use of chorionic villi enabled a diagnosis within a few hours after sampling in the ninth week of pregnancy whereas the use of amniotic fluid cells in the earlier case required two weeks of culturing after amniocentesis in the 16th week. Four female fetuses were found; heterozygosity was demonstrated in one by analysis of clones in the primary amniotic fluid cell culture.
 ...
PMID:Prenatal diagnosis of Fabry's disease by direct analysis of chorionic villi. 303 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>