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

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

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

In July 2009, a 14-yr-old male caracal (Caracal caracal) at the National Zoological Gardens of South Africa was found, on abdominal ultrasound, to have a single large cystolith. The cystolith was removed, and the composition was determined to be 100% cystine. Blood and urine samples were also collected from three other apparently healthy caracals at the zoo and were submitted, together with the samples from the affected animal, for analysis using gas chromatograph mass spectrometry for cystine, lysine, alanine, and ornithine levels. The cystine levels in the urine, the fractional excretion of cystine, and the normalized excretion of cystine (micromol/g of creatinine) were all higher in the affected caracal than in the healthy animals. Only a single other case of cystine urolithiasis has been previously reported in any wild felid in the literature.
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PMID:Cystine urolithiasis in a caracal (Caracal caracal). 2308 35

Urolithiasis is a complex and multifactorial disorder characterized by the presence of stones in the urinary tract. Urea cycle is an important process involved in disease progression. L-ornithine is a key amino acid in the urea cycle and is converted to putrescine by ornithine decarboxylase (ODC). Putrescine, spermidine and spermine are natural polyamines that are catabolized by a specific enzyme, spermidine/spermine acetyltransferase (SSAT). The single-nucleotide polymorphisms (SNPs) in the intron region of ODC (+316 G>A) and promoter region of SSAT (-1415 T>C) genes have been found to be associated with the polyamines expression levels. The aim of this study was to examine whether the ODC (+316 G>A) intron 1 region gene polymorphism and SAT-1 promoter region (-1415 T>C) gene polymorphisms are potential genetic markers for susceptibility to urolithiasis. A control group of 104 healthy subjects and a group of 65 patients with recurrent idiopathic calcium oxalate stone disease were enrolled into this study. Polymerase chain reaction (PCR)-based restriction analysis was performed for the ODC intron 1 (+316 G>A) region and SAT-1 (-1415 T>C) promoter gene polymorphisms by PstI and MspI restriction enzyme digestion, respectively. The genotype distribution of polymorphisms studied in the ODC intron 1 region (+316 G>A) and SAT-1 -1415 T>C promoter region did not reveal a significant difference between urolithiasis and the control groups (P=0.713 and 0.853), respectively. Furthermore, no significant difference was observed between the control and patient groups for ODC +316 G>A and SAT-1 -1415 T>C allele frequencies (P=0.877 and 0.644), respectively. In conclusion, results of the present study suggest that ODC + 316 G>A and SAT-1 -1415 T>C gene polymorphisms might not be a risk factor for urolithiasis.
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PMID:Lack of evidence for the association of ornithine decarboxylase (+316 G>A), spermidine/spermine acetyl transferase (-1415 T>C) gene polymorphisms with calcium oxalate stone disease. 2464 71

Cystinuria is an autosomal inherited disorder of renal reabsorption of cystine, arginine, lysine, and ornithine. Increased urinary excretion of cystine results in the formation of kidney stones. Considering the few studies on the genetic basis of the cystinuria in the Middle East and the population-specific distribution of mutations in the SLC3A1 and SLC7A9 genes, in the present study, mutation analysis of these two genes was performed in a cohort of Iranian patients with cystinuria. Thirty unrelated cystinuria patients were analyzed for four of the most common mutations using ARMS-PCR (M467T, T216M) and RFLP-PCR (G105R, R333W) methods. For negative sample, two exons of both genes, which harbor many mutations, were subject to DNA sequencing. Eight variants were identified including missense, polymorphism, intron variant, and a novel variant. The most frequent mutations were not detected in our patients and only G105R was found. Since the molecular genetic testing results may influence the therapy and prognosis of cystinuria, this paper contributes to understanding of the molecular basis of cystinuria in the Iranian patients.
Urolithiasis 2015 Oct
PMID:Mutation analysis of SLC3A1 and SLC7A9 genes in patients with cystinuria. 2612 50


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