Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 10-month-old male Siamese cat with dysuria was determined to have cystine crystalluria. Many small calculi composed entirely of cystine were found in the urinary bladder. Measurement of serum and urine amino acids and calculation of fractional reabsorption of amino acids indicated reabsorption defects for cystine, ornithine, lysine, and arginine. Urinary acidification, fractional reabsorption of glucose, and fractional reabsorption of electrolytes were normal. Diagnoses of cystinuria and cystine urolithiasis were made on the basis of low fractional reabsorption of cystine and dibasic amino acids and the detection of cystine calculi in the urinary bladder.
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PMID:Cystinuria in a cat. 199 60

Cystinuria is an hereditary disorder of renal and intestinal transport characterized by the excessive urinary excretion of cystine, arginine, lysine, and ornithine. It is inherited as a common recessive gene with allelic mutations. Complementary studies of the plasma response to oral cystine loading, intestinal mucosal transport patterns, and urine cystine excretion allow separation of homozygous cystinuric subjects into three groups. In type I, the most common form, there is no active transport of cystine or dibasic amino acids across the mucosal gradient, and heterozygous subjects show normal urine cystine values. Type II is characterized by markedly reduced or absent intestinal transport of cystine. Heterozygotes for type II show significantly elevated urine cystine but less than is seen in homozygotes. In type III there is diminished, although demonstrable, intestinal absorption of cystine and dibasic amino acids. Urine cystine in heterozygotes is intermediate between types I and II. Urolithiasis with its attendant complications is the sole clinical manifestation of cystinuria and is due to the relative insolubility of cystine in the urine. The urolithiasis may become clinically manifest at any time from infancy through the ninth decade, although the mean age is the second to third decade. Clinical presentation is similar to that of other types of urolithiasis. Although cystinuria accounts for only 1% to 2% of all urolithiasis and 6% to 8% of urolithiasis in pediatric populations, repeated stone formation in affected patients often causes considerable morbidity. Cystine crystals in the urine are diagnostic but show up in only 19% to 26% of homozygous cystinuric patients. Sodium cyanide nitroprusside is a suitable screening test that should identify homozygous stone formers but will not detect all heterozygotes. A positive screening test should be followed by quantitation of urinary amino acids. A homozygous patient can be functionally defined as one who excretes 250 mg or more of cystine/g of creatinine in a 24-hour urine collection. Other causes of excess urinary cystine must be excluded. Medical therapy will be directed toward dissolution of existing calculi and prevention of new stone formation. Increasing urine volume by generous oral fluid intake is beneficial. Dietary sodium restriction has a favorable effect on urinary cystine excretion. Cystine solubility can be improved by urinary alkalinization and where necessary by the administration of thiol chelators, particularly D-penicillamine or mercaptopropionylglycine. Because these chelators have significant adverse effects, they should be reserved for patients who do not respond to a more conservative program. Patients with infected, symptomatic, or obstructing stones require surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cystinuria. 208 17

Cystinuria is a recessively inherited transport disorder, with at least three mutant alleles (I, II, and III) demonstrable. I/I, II/II, and III/III homozygotes and I/II, I/III, and II/III compound heterozygotes (cystinuric patients) have high urinary concentrations of cystine, lysine, arginine, and ornithine and frequently form cystine stones. +/I heterozygotes (nondetectable) are phenotypically normal, whereas +/II and +/III heterozygotes (detectable) show variable increases in urinary cystine and lysine concentration and at times increases in urinary arginine levels. The objectives of the present study were to determine the frequency of +/II heterozygotes among stone-forming and nonstone-forming individuals from the same region of Brazil and to evaluate the possible relationship between heterozygous cystinuria and urinary lithiasis. When urine samples from 5,150 individuals (5,000 nonstone-forming individuals and 150 stone-forming individuals) were screened by the qualitative cyanide-nitroprusside cystine test, by thin-layer amino acid chromatography, and by quantitative amino acid determination by ion-exchange chromatography, 32 +/II or +/III heterozygotes (26 nonstone-forming and six stone-forming individuals) were detected. The frequency of detectable heterozygotes among the stone-forming individuals (1:25) was significantly higher than that among nonstone-forming individuals (1:104), which provides additional evidence that heterozygosity for +/II and +/III cystinuria is a risk factor in the formation of urinary stones. No significant difference was detected in urinary cystine concentration or in terms of the various characteristics of urolithiasis when stone-forming heterozygotes were compared to nonstone-forming heterozygotes. These data suggest that the tendency towards stone-forming among heterozygotes is probably owing to a complex and multifactorial mechanism.
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PMID:Heterozygous cystinuria and urinary lithiasis. 393 71

Human urine contains several macromolecules which inhibit calcium oxalate crystallization. Osteopontin (or uropontin), a secreted phosphoglycoprotein with the amino acid sequence Arg-Gly-Asp (RGD) and high affinity to hydroxyapatite, is one such inhibitor. To investigate the action of this protein on renal stone formation, the expression osteopontin gene in normal and chemically induced urolithiasis rat kidney was compared at both mRNA and protein levels. Northern blot analysis shown a significant increase of osteopontin mRNA level in stone-forming rat kidney compared with normal ones. In an in situ hybridization study, we localized the transcripts of the osteopontin gene in epithelial cells of both distal and collective tubules, and found a remarkably strong signal in stone-forming rats. The amount and distribution of the protein in kidney from immunocytochemistry staining showed the same pattern as seen in situ hybridization. These findings indicate that osteopontin may be an important macromolecule in the normal endogenous defence against the formation of urinary calculi.
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PMID:Expression of osteopontin mRNA in normal and stone-forming rat kidney. 987 18

Proton Nuclear Magnetic Resonance (NMR) Spectroscopy of urine (as well as of other biological fluids) is a very powerful technique enabling multi-component analysis useful in both diagnosis and follow-up of a wide range of inherited metabolic diseases. Among these pathologies, cystinuria is characterised by accumulation in urine of four dibasic amino acids, namely lysine, arginine, ornithine and cystine; the last one, being only slightly water soluble, generates urolithiasis. The mentioned aminoacids can be detected in the urine NMR spectrum of cystinuric patients, the most abundant being the lysine (5 mM and over are often detected), whose typical signals become very high; arginine and ornithine are also usually detectable, although pathologic concentrations are lower (usually below 2mM). The proposed NMR technique is also suitable in monitoring the therapy with alpha-mercaptopropionylglycine (MPG), providing quantitation of several metabolites of interest in the follow-up of the pathology, like cystine, creatinine and citrate.
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PMID:Diagnosis and follow-up of cystinuria: use of proton magnetic resonance spectroscopy. 1112 53

The formation of urinary stones is associated with cell death in response to various injuries. P21 (WAF1/CIP1) is a downstream protein of P53 and can arrest the cell cycle at G1/S with resulting cell death. We aimed to investigate the polymorphism of p2 gene codon 31 as the genetic marker in searching for the association of urolithiasis. One hundred and nineteen healthy controls and 95 patients with calcium oxalate stone were examined in this study. The polymorphism was seen from the result of polymerase chain reaction-based restriction analysis. The result revealed significant differences between normal individuals and stone patients (P < 0.05) and the distribution of arginine homozygote in the control group (31.9%) was higher than in the patient group (16.8%). It is concluded that polymorphisms of p21 codon 31 can be a genetic marker for urinary stone disease. Individuals possessing arginine form of p21 codon 31 have less risk of developing calcium stone disease.
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PMID:Arginine form of p21 gene codon 31 is less prominent in patients with calcium oxalate stone. 1139 35

Cystinuria is an autosomal recessive disorder with an estimated incidence of 1 case in 7000 live births, that results in elevated urinary excretion of cystine and dibasic aminoacids: ornithine, lysine and arginine. Discussed by Sir Archibald Edward Garrod, in 1908, as one of the four first known inborn errors of metabolism, it is characterized by a defect in transport of cystine and dibasic aminoacids, that affects their reabsortion in both renal tubule and gastrointestinal tract. To date, according to the recent molecular findings, two genes have been identified as responsible for this disease: SLC3A1 and SLC7A9. A more accurate pheno/genotyping identification of cystinuric patients will allow to improve prophilaxis and therapy for this illness. Cystinuria only causes recurrent urolithiasis (about 1-2 / of renal calculi in adults) and its associated complications as clinical feature because of poor cystine solubility at low pH. An accurate control over prohylaxis (based on high water intake and potassium citrate treatment, on first line, and tiol-derivatives treatment, on second line) must be taken in patients -like homozygous type I- with high lithiasis risk. However, approximately one half of patients under prophylaxis control will develop recurrent lithiasis; in this case, only urology or surgical approaches would be possible. 474 Updated knowledge about biochemical, genetic, clinical, diagnosis, prevention, treatment and prognosis aspects of this, relatively unusual, disease has been reviewed in this article.
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PMID:[Cystinuria update: clinical, biochemical and genetic aspects]. 1284 5

Cystinuria, one of the most common inborn errors of metabolism in humans, accounts for 1-2% of all cases of renal lithiasis. It is caused by defects in the heterodimeric transporter system rBAT/b0,+AT, which lead to reduced reabsorption of cystine and dibasic amino acids through the epithelial cells of the renal tubules and the intestine. In an N-ethyl-N-nitrosourea mutagenesis screen for recessive mutations we identified a mutant mouse with elevated concentrations of lysine, arginine and ornithine in urine, displaying the clinical syndrome of urolithiasis and its complications. Positional cloning of the causative mutation identified a missense mutation in the solute carrier family 3 member 1 gene (Slc3a1) leading to an amino acid exchange D140G in the extracellular domain of the rBAT protein. The mouse model mimics the aetiology and clinical manifestations of human cystinuria type I, and is suitable for the study of its pathophysiology as well as the evaluation of therapeutic and metaphylactic approaches.
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PMID:A mouse model for cystinuria type I. 1292 63

Cystinuria is a hereditary disorder of cystine and dibasic amino acids (lysine, arginine, ornithine) transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. Cystine stones frequently occur in the second or third decade of life with an occasional occurrence in infancy and in old age. Herein is presented the case of a 1-year-old girl with cystinuria and recurrent urolithiasis; the genetic basis of the disease was investigated by mutational analysis of the SLC3A1 gene. The data show that the present patient has an increased cystine (923.08 microg/mL) level and was heterozygote for M467T mutation.
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PMID:Analysis of a 1-year-old cystinuric patient with recurrent renal stones. 1701 17

Renal hypouricemia (MIM 220150) is an inherited disorder characterized by low serum uric acid levels and has severe complications such as exercise-induced acute renal failure and urolithiasis. We have previously reported that URAT1/SLC22A12 encodes a renal urate-anion exchanger and that its mutations cause renal hypouricemia type 1 (RHUC1). With the large health-examination database of the Japan Maritime Self-Defense Force, we found two missense mutations (R198C and R380W) of GLUT9/SLC2A9 in hypouricemia patients. R198C and R380W occur in highly conserved amino acid motifs in the "sugar transport proteins signatures" that are observed in GLUT family transporters. The corresponding mutations in GLUT1 (R153C and R333W) are known to cause GLUT1 deficiency syndrome because arginine residues in this motif are reportedly important as the determinants of the membrane topology of human GLUT1. Therefore, on the basis of membrane topology, the same may be true of GLUT9. GLUT9 mutants showed markedly reduced urate transport in oocyte expression studies, which would be the result of the loss of positive charges in those conserved amino acid motifs. Together with previous reports on GLUT9 localization, our findings suggest that these GLUT9 mutations cause renal hypouricemia type 2 (RHUC2) by their decreased urate reabsorption on both sides of the renal proximal tubule cells. However, a previously reported GLUT9 mutation, P412R, was unlikely to be pathogenic. These findings also enable us to propose a physiological model of the renal urate reabsorption via GLUT9 and URAT1 and can lead to a promising therapeutic target for gout and related cardiovascular diseases.
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PMID:Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2). 2213 64


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