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)

Angiokeratoma corporis diffusum (Fabry disease) is an X-linked recessive disease. We had an opportunity to examine a heterozygous female patient with angiokeratoma and cornea verticillata. The patient's serum alpha-galactosidase activity was reported to be about 50% of normal. Skin lesion biopsy specimens were stained with electron microscopic acid phsophatase (ACP), with proper controls. Acid phosphatase activity was demonstrable within membrane-bound inclusions of cutaneous vascular endothelial cells. This suggested that the accumulation of abnormal glycolipids in the vascular cells occurs in the lysosomes.
 ...
PMID:Angiokeratoma corporis diffusum (Fabry disease). A lysosomal disease. 18 6

A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity.
 ...
PMID:Neurological manifestations of Fabry disease in female carriers. 21 99

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.
 ...
PMID:Fabry's disease in a black kindred. 22 50

Fabry's disease (angiokeratoma corporis diffusum universale) is an inborn error of metabolism, which is based on a shortage in the cumulation of glycosphingolipids in endothelial and epithelial cells of glomeruli, vascular endothelia and in ganglion cells with subsequent severe organ damage. Heredity is X-linked recessive. In the submitted paper the authors present a case-history of a family where three men were affected and carriership was confirmed in five women. During the first pregnancy one of them a successful prenatal diagnosis was made from cultivated amniotic fluid cells. Chromosomal examination revealed female sex and the levels of the alpha-galactosidase A were established in cultivated cells. A healthy girl was delivered.
 ...
PMID:[Present possibilities of prenatal diagnosis of Fabry's disease]. 148 71

The authors undertook a clinical and genetic study in a large family with the aim of identifying the mode of inheritance of Fabry syndrome and congenital ptosis. These two types of pathology were present to varying extents. The family pedigree consisted of 95 individuals, spanning 5 generations. Three individuals (males) were found to have Fabry syndrome and 14 (males and females) congenital ptosis. The patients with Fabry syndrome also had congenital ptosis. According to these results, Fabry syndrome is inherited by an X-linked recessive mode and congenital ptosis by an autosomal dominant mode.
 ...
PMID:[Familial coexistence of the association: Fabry's syndrome and congenital ptosis]. 177 4

Fabry's disease is a rare progressive X-linked recessive disorder of glycosphingolipid metabolism. The accumulation of glycosphingolipids occurs in virtually all areas of the body, including the endothelial, perithelial, and smooth-muscle cells of blood vessels, the ganglion cells of the autonomic nervous system, and the glomeruli and tubules of the kidney. Although otologic symptoms have been described in these patients, to our knowledge there have been no temporal bone histopathologic reports. We describe the clinical histories, audiometric results, and temporal bone findings of two patients with this rare disorder. Both patients demonstrated a bilateral sloping sensorineural hearing loss audiometrically. Middle ear findings of seropurulent effusions and hyperplastic mucosa were seen in all four temporal bones. Strial and spiral ligament atrophy in all turns, and hair cell loss mainly in the basal turns, were also common findings. The number of spiral ganglion cells was reduced in all temporal bones; however, evidence of glycosphingolipid accumulation was not observed in the spiral ganglia.
 ...
PMID:Otologic histopathology of Fabry's disease. 249 91

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

Originally described as a dermatologic curiosity by Fabry in 1898 and independently by Anderson in the same year, Fabry disease is now recognized as an inborn error of glycosphingolipid metabolism resulting from the defective activity of the lysosomal enzyme, alpha-galactosidase A (see Desnick and Sweeley for a comprehensive review). The enzymatic defect, transmitted by an X-linked recessive gene, leads to the accumulation of neutral glycosphingolipids with terminal alpha-galactosyl residues in the plasma and in the lysosomes of endothelial, perithelial, and smooth muscle cells of the cardiovascular-renal system and, to a lesser extent, in reticuloendothelial, myocardial, and connective tissue cells. Epithelial cells in the kidney, cornea, and other tissues contain the lysosomal depositions, as do the ganglia and perineural cells of the autonomic nervous system. The major accumulated substrate is globotriaosylceramide [galactosyl-(alpha 1----4)-galactosyl-(beta 1----4)-glucosyl-(beta 1----1')-ceramide]; another substrate, galabiosylceramide [galactosyl-(alpha 1----4)-galactosyl-(beta 1----1')-ceramide] is deposited primarily in renal lysosomes. The clinical manifestations of Fabry disease are the sequelae of the anatomical and physiologic alterations produced by progressive glycosphingolipid deposition. Clinical onset of the disease in hemizygous males usually occurs during childhood or adolescence, with periodic crises of severe pain in the extremities (acroparesthesias), the appearance of the vascular cutaneous lesions (angiokeratoma), hypohidrosis, and the characteristic corneal dystrophy. With increasing age, the major morbid symptoms of the disease result from the progressive infiltration of glycosphingolipid in the cardiovascular-renal system. Death usually occurs from renal, cardiac, or cerebral complications of the vascular disease. Prior to the availability of treatment by renal transplantation or dialysis, the average age at death for affected males was about 40 years. Heterozygous females, who may exhibit the disease in an attenuated form, are most likely to have only corneal opacities. Previously, the diagnosis of affected hemizygous males and heterozygous females was based on clinical findings and the levels of alpha-galactosidase A activity in easily obtained sources, e.g., plasma and isolated lymphocytes or granulocytes. Because the gene encoding alpha-galactosidase A undergoes random X-inactivation, the expressed level of enzymatic activity in females heterozygous for the disease gene may vary significantly, thereby making accurate carrier detection difficult.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Fabry disease: molecular genetics of the inherited nephropathy. 256 47

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

Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase A, which leads to the pathologic deposition of neutral glycosphingolipids in lysosomes of the vascular endothelium of the heart, brain and kidney. The disease is progressive in hemizygous male patients, with increasing involvement of the major organs leading to death. Because cardiac involvement is a constant feature, echocardiograms were performed on 35 patients with Fabry's disease, 23 hemizygotes (aged 28.6 +/- 14 years) and 12 heterozygotes (aged 31.6 +/- 6 years), to determine whether cardiac involvement could be detected noninvasively. The results demonstrated that hemizygous male patients had a greater aortic root diameter, thicker interventricular septum and greater ventricular mass than did heterozygous female patients. Left ventricular mass per square meter of body surface area correlated well with clinical disease severity (r = 0.68, p less than 0.05), suggesting progressive glycosphingolipid deposition. Older heterozygotes (greater than 25 years old) had more severe evidence of cardiac disease than did younger male patients. Although mitral valve prolapse was identified in 12 (54%) of 23 male hemizygotes and in 7 (58%) of 12 female heterozygotes its presence did not correlate with clinical disease severity or other echocardiographic variables. Therefore, echocardiographic evidence of Fabry's disease appears to correlate with age-related disease severity and may be a useful noninvasive marker to follow disease progression and possible regression when appropriate therapy becomes available.
 ...
PMID:Echocardiographic abnormalities and disease severity in Fabry's disease. 308 58


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