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)

The properties of the residual alpha-galactosidase activity in kidney, liver, spleen, fibroblasts and urine of a Fabry hemizygote have been studied using p-nitrophenyl-alpha-galactoside and 4-methylumbelliferyl-alpha-galactoside as substrates. In addition, alpha-galactosidase activity in urine has been determined with ceramidetrihexoside as substrate. The residual alpha-galactosidase activity of Fabry, measured with artificial substrate, is stimulated (6-35%) by myo-inositol and only slightly inhibited by melibiose (7-17%) in all the materials used. In contrast, the alpha-galactosidase of normal tissues and urine is inhibited (36-48%) by myo-inositol and inhibited to a much greater extent (40-50%) by melibiose. The KM for artificial substrate of the residual activity of Fabry is higher than that of the alpha-galactosidase in normal kidney, liver, spleen, fibroblasts and urine. The residual activity of Fabry is generally more stable to heating than the activity in the normal materials, although exceptions were noted. When these properties are compared with those of the alpha-galactosidase isoenzymes in normal tissues and body fluids, the residual activity of Fabry material seems to be very similar to the minor component of normal tissue (alpha-galactosidase B). Moreover, the pH optimum curve of this minor component and of the Fabry alpha-galactosidase in urine are similar, whereas the major isoenzyme (alpha-galactosidase A) shows a curve much more like that of normal urine. The findings with ceramidetrihexoside as substrate indicate a possible discrepancy. Alpha-Galactosidase A hydrolyses ceramidetrihexoside, Fabry urine preparation does not. However, alpha-galactosidase B of normal urine shows a slight but definite ceramidetrihexosidase activity. No contamination of the B preparation with alpha-galactosidase A could be detected. The minimum hypothesis, supported by most of the experimental evidence, is that the residual activity of Fabry and normal alpha-galactosidase B are identical.
 ...
PMID:Properties of the residual alpha-galactosidase activity in the tissues of a Fabry hemizygote. 80 16

Two patients with Fabry's disease were infused with normal plasma to provide active enzyme (ceramide trihexosidase) for hydrolysis of the plasma substrate, galactosylgalactosylglucosylceramide. Maximum ceramide trihexosidase activity occurred 6 hours after infusion of the plasma, attaining a level approximately 150 percent of that in normal plasma; enzymatic activity was detectable for 7 days. The amount of accumulated substrate in the plasma of these recipients decreased about 50 percent on day 10 after infusion. Thus, periodic replacement of ceramide trihexosidase activity in the plasma of patients with Fabry's disease might lead to consistently lower amounts of substrate in the plasma and a decrease in its rate of accumulation in tissues.
 ...
PMID:Enzyme replacement in Fabry's disease, an inborn error of metabolism. 491 26

We report renal lesions and functional alterations in a 32-year-old man with Fabry's disease (ceramidetrihexosidase deficiency). By light microscopy of a renal biopsy specimen, distinctive "foamy" cytoplasmic alterations were observed in renal glomerular, tubular, vascular, and interstitial cells. Histochemical analysis of vacuolated epithelial cells showed glycolipid- and phospholipid-like material. Ultrastructurally, dense osmiophilic as well as stacked and concentric laminated profiles were observed within these epithelial cells. In addition, glomerular endocapillary, parietal, and vascular epithelial cells contained opaque osmiophilic granular deposits with paracrystalline arrays. Renal function studies indicated a glomerular filtration rate of 86.1 mL/min/1.73 sq m, effective renal plasma flow of 415 mL/min/1.73 sq m, tubular reabsorption of glucose of 356 mg/min/100 glomerular filtration rate, and maximal urinary concentrating and diluting ability of 568 and 46 mOsm/kg, respectively. Serum ceramide hexosidase activity was 0.18 nmole/hr/mL (normal, 8 to 15). We conclude that renal dysfunction associated with Fabry's disease is associated mainly with accumulation of glycolipid and phospholipid compounds in the walls of blood vessels and distal nephrons.
 ...
PMID:Clinicopathologic, enzymatic, and genetic features in a case of Fabry's disease. 676 61

Fabry's disease is an X-linked recessive Lysosomal Storage disease. The underlying metabolic defect is deficiency of lysosomal enzyme ceramidetrihexosidase. The disease has multisystem involvement. Neurological manifestations include small-fiber polyneuropathy manifested as painful distal extremities and anhidrosis. Fabry's disease also presents with both small-vessel and cortical multiple cerebral infarcts. Enzyme-replacement therapy has been found effective but expensive. Gene therapy could evolve as the ultimate therapeutic strategy.
 ...
PMID:Fabry disease with special reference to neurological manifestations. 1574 87

Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of a-galactosidase A (also known as ceramide trihexosidase) and resultant accumulation of globotriaosylceramide (Gb3) and related glycophospholipids. The disease affects nearly all major organ systems, with the primary sites damaged by Gb3 including renal glomeruli, myocardium, neurons of the dorsal ganglion and autonomic nervous system, and vascular endothelial and smooth muscle. Progressive deposition in these organ systems leads to renal and heart failure; debilitating pain as a result of nervous system involvement also occurs.
...
PMID:Acroparesthesia in a female: diagnostic dilemma. 2553 Jul 62

In 1898 William Anderson and Johannes Fabry described the red-purple maculopapular skin lesions characteristic for Fabry disease and also mentioned the presence of proteinuria. Four decades later Maximiliaan Ruiter concluded that angiokeratoma corporis diffusum is the cutaneous manifestation of an inherited systemic internal disease. In 1947 autopsy findings of two cases who died from uraemia revealed sclerosis of glomeruli. At this time the presence of a thesaurismosis was also considered. The first renal needle biopsy in 1958 showed vacuolation and distension of the cells of the glomerular tufts and distal tubules suggestive of a storage disorder. The ability to concentrate the urine was also impaired in these patients. Sweely und Klionsky in 1963 demonstrated that the major storage component is a trihexoside. As of 1967 Roscoe Brady finally described the deficiency of the enzyme ceramidetrihexosidase/-galactosidase A characteristic in patients with Fabry disease.
...
PMID:The Renal History of Fabry Disease. 2691 82