Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported previously two siblings with gout and uric acid lithiasis associated with excessive purine production. In the erythrocytes of these patients, phosphoribosylpyrophosphate (PRPP) synthetase exhibited resistance to feedback-inhibition by normal cell constituents such as guanosine-5'-diphosphate (GDP) and adenosine-5'-diphosphate (ADP), resulting in superactivity of the mutant enzyme and consequently in increased PRPP content and availability for nucleotide synthesis. Erythrocyte PRPP content and availability were normal in the propositus' parents, his healthy brother and three sons, and they all had normal serum level and urinary excretion of uric acid, except for the mother who was hyperuricosuric. To further characterize this mutation we studied PRPP and purine metabolism in cultured fibroblasts of the affected family. PRPP synthetase in dialyzed lysates of fibroblasts from the propositus and his mother exhibited increased specific activity, more markedly at low inorganic phosphate concentration, and decreased sensitivity to inhibition by ADP and GDP, PRPP content and availability and the rate of de novo purine nucleotide synthesis were markedly increased in the fibroblasts of the propositus and to a lesser extent in the fibroblasts of his mother but were normal in the fibroblasts of the other family members investigated. The fibroblast studies demonstrate the following sequence of abnormalities: feedback-resistance of PRPP synthetase; superactivity of this enzyme in normal physiological milieu; increased availability of PRPP; and increased de novo synthesis of purine nucleotides. The pattern of inheritance of this disorder is compatible with both an X-linked recessive and autosomal dominant traits.
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PMID:Mutant feedback-resistant phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. Phosphoribosylpyrophosphate and purine metabolism in cultured fibroblasts. 17 Dec 80

On the basis of a study of the action of phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1.) in 22 hyperuricemic and 9 normal subjects, the authors report two cases of gout with anomalies of the kinetics of this enzyme. The anomaly consists of an increase in affinity for inorganic phosphate (iP) in the absence of inhibitors, and a decrease in inhibition by low concentrations of ADP in the presence of iP. These patients show no other anomaly of intraerythrocyte PRPP (dosage and production "in vitro"), hypoxanthine-guanine-phosphoribosyl-transferase and APRTase (overall activity and apparent Km). These two cases of gout are characterized clinically by their early occurrence, appearing in one case in a pre-menopausal woman, their family character and their normal sensitivity to allopurinol.
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PMID:[Phosphoribosylpyrophosphate synthetase anomalies in 2 cases of gout beginning at an early age]. 22 83

The significance of partial deficiency of erythrocyte adenine phosphoribosyltransferase (APRT), reported in a number of subjects with gout, has been investigated by studying its incidence in 700 normal blood donors. Three clearly deficient subjects were found, an incidence not significantly different from that in patients with abnormalities of urate metabolism. A new assay method for APRT is described in which an erythrocyte lysate is incubated with adenine and phosphoribosylpyrophosphate (PRPP) for a given time; both hemoglobin and adenine nucleotide (AMP) are then precipitated with lanthanum phosphate; the change in absorbance of adenine at 260 nm reflects the extent of its conversion to AMP by APRT.
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PMID:Adenine phosphoribosyltransferase: a simple spectrophotometric assay and the incidence of mutation in the normal population. 86 96

Serum and 24-hour urinary phosphate levels in primary gout patients and control subjects were measured. About 45% of gouty patients showed mild hypophosphatemia. However, mean 24-hour urinary excretion of phosphate was significantly elevated as compared with that of controls. Gouty patients showed a significantly decreased tubular reabsorption of phosphate and renal phosphate threshold. It seems that tubular phosphate transport in gouty patients is impaired, and this is the major cause of hypophosphatemia.
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PMID:Decreased renal phosphate threshold in patients with gout. 143 4

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.
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PMID:Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. 150 84

The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium pyrophosphate dihydrate gout and other crystal deposition diseases. 165 74

A method using high-performance liquid chromatography (HPLC) for determination of phosphoribosylpyrophosphate (PRPP) synthetase activity in human erythrocytes has been developed and PRPP synthetase activity on purine and pyrimidine metabolic disorders has been studied. Kinetic properties of erythrocyte PRPP synthetase of patients with gout and of a patient with pyrimidine 5'-nucleotidase deficiency were compared with those of healthy subjects. The mean of PRPP synthetase activity of gouty patients was a little higher (P less than 0.01) than that of healthy subjects. The response of the enzyme for ATP of gouty patients was different from that of healthy subjects. The shapes of activation curve of the enzyme for inorganic phosphate were hyperbolic in gouty patients and in a patient with pyrimidine 5'-nucleotidase deficiency.
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PMID:Phosphoribosylpyrophosphate synthetase in human erythrocytes: assay and kinetic studies using high-performance liquid chromatography. 166 46

Arthritis, which can be acute, chronic or asymptomatic, is caused by a variety of crystal deposition in joints. The three main types of crystal arthritis are monosodium urate (gout), calcium pyrophosphate dihydrate, and calcium phosphate (usually hydroxyapatite). A clinical approach to diagnosis and management.
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PMID:Crystal arthritis: a clinician's view. 180 73

The hyperuricemia responsible for the development of gouty arthritis results from a wide range of environmental factors and underlying genetically determined aberrations of metabolism. 31P magnetic resonance spectroscopy studies of children with hereditary fructose intolerance revealed a readily detectable rise in phosphomonoesters with a marked fall in inorganic phosphate in their liver in vivo and a rise in serum urate in response to very low doses of oral fructose. Parents and some family members heterozygous for this enzyme deficiency showed a similar pattern when given a substantially larger dose of fructose. Three of the nine heterozygotes thus identified also had clinical gout, suggesting the possibility of this defect being a fairly common cause of gout. In the present study this same noninvasive technology was used to identify the same spectral pattern in 2 of the 11 families studied with hereditary gout. In one family, the index patient's three brothers and his mother all showed the fructose-induced abnormality of metabolism, in agreement with the maternal inheritance of the gout in this family group. The test dose of fructose used produced a significantly larger increment in the concentration of serum urate in the patients showing the changes in 31P magnetic resonance spectra than in the other patients with familial gout or in nonaffected members, thus suggesting a simpler method for initial screening for the defect.
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PMID:Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy. 223 43

The recognition of tissue deposits of crystalline material in a variety of organs, including the kidney, predated the association of crystals and arthritic disease. Because of this, the pathophysiology of crystal formation and its resultant inflammation is based in part on studies of renal stones. A number of disease states involving renal and articular crystallization exist. The most common of these, uric acid precipitation, or gout, and calcium phosphate precipitation were not reviewed in this discussion. This review described a variety of less common disease states involving articular and renal crystal deposition. The renal diseases discussed included both parenchymal or ectopic crystal deposition, as seen in nephrocalcinosis or cystinosis, and ductal crystallization as seen in renal calculus disease. The crystals involved included not only calcium oxalate, but also aluminum, amino acids and proteins (cystine, hemoglobin, cryoglobulins, and immunoglobulins), purine metabolites (xanthine, hypoxanthine), and even lipids and their degradative enzymes (cholesterol, phospholipids, phospholipase, and fatty acids). The simultaneous occurrence of crystals in both kidneys and joints was found in some cases to result from the systemic deposition of an excess of a particular biological compound. However, of more interest, some renal deposits were shown to more selectively reflect the normal or abnormal function of the kidney in its secretory and excretory roles. This is particularly evident in the variety of arthritic states described in end-stage renal disease.
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PMID:Calcium oxalate and other crystals associated with kidney diseases and arthritis. 264 79


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