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)

Homozygous deficiency of a purine salvage enzyme, adenine phosphoribosyltransferase (APRT), causes urolithiasis and renal failure. There are two known types of homozygous APRT deficiencies; type I patients completely lack APRT activity while type II patients only partially lack such activity. All type II patients possess at least one APRT*J allele with a substitution from ATG (Met) to ACG (Thr) at codon 136. Type I patients are considered to possess two alleles (APRT*Q0) both of which code for complete deficiencies. Thus, some patients with type II APRT deficiencies may have a genotype of APRT*J/APRT*Q0. As no individuals with such a genotype have previously been identified, we performed extensive analysis on four members of a family by (1) the T-cell method for the identification of a homozygote, (2) the B-cell method for the identification of heterozygotes, and (3) oligonucleotide hybridization after in vitro amplification of a part of genomic APRT sequence for the identification of APRT*J and non-APRT*J alleles. We report here the first evidence that 2,8-dihydroxyadenine urolithiasis developed in a boy aged 2 years with a genotype of APRT*J/APRT*Q0.
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PMID:Identification of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APART*Q0) leading to 2,8-dihydroxyadenine urolithiasis. 222 34

Adenine phosphoribosyltransferase (APRT) deficiency causing 2,8-dihydroxyadenine urolithiasis and renal failure is present at a high frequency among the Japanese but not other ethnic groups. A special type of mutant allele, designated APRT*J, with a nucleotide substitution at codon 136 from ATG (Met) to ACG (Thr) is carried by approximately 79% of all Japanese 2,8-dihydroxyadenine urolithiasis patients. We analyzed mutant alleles of 39 APRT deficient patients using a specific oligonucleotide hybridization method after in vitro amplification of a part of the genomic APRT sequence. We found that 24 had only APRT*J alleles. Determination of the haplotypes of 194 APRT alleles from control Japanese subjects and of the 48 different APRT*J alleles indicated that normal alleles occur in four major haplotypes, whereas all APRT*J alleles occur in only two. These results suggest that all APRT*J alleles have a single origin and that this mutant sequence has been maintained for a long period, as calculated from the frequency of the recombinant alleles.
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PMID:Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. 222 51

Urinary acidification previously was shown to be an effective treatment for calcium-induced urolithiasis in domestic fowl, but diuresis caused by the acidifying agent (ammonium chloride) was an undesirable side effect. Because supplemental dietary methionine reportedly acidifies mammalian urine, an experiment was conducted to evaluate the efficacy of the free acid form of methionine hydroxy analog (MHA) as an acidifying agent for treating avian urolithiasis. From 5 to 17 wk of age, immature Single Comb White Leghorns were fed diets containing normal calcium (1%) or high calcium (3.5%). Diets were supplemented with 0, 0.3 or 0.6% MHA. Relative to birds fed the normal calcium diets, birds fed the high calcium diet without added MHA were in a state of metabolic alkalosis and excreted more alkaline urine containing high levels of calcium. Birds fed the high calcium diet without MHA also had significantly higher kidney asymmetry ratios, a higher incidence of gross kidney damage, and a higher incidence of urolith formation when compared with birds fed normal calcium diets. When compared with the high calcium diet without MHA, the high calcium diet supplemented with 0.6% MHA significantly acidified the urine without causing detectable metabolic acidosis, significantly reduced kidney asymmetry and gross kidney damage, and reduced the incidence of urolith formation without increasing water consumption or urine flow. These data demonstrate that MHA effectively prevents calcium-induced kidney damage in domestic fowl without causing undesirable side effects. MHA did increase both fractional and absolute calcium excretion during calcium loading.
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PMID:Methionine hydroxy analog (free acid) reduces avian kidney damage and urolithiasis induced by excess dietary calcium. 272 31

Complete adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine urolithiasis. In previous reports, analysis of the kinetic properties of APRT from APRT-deficient Japanese subjects revealed strikingly similar abnormalities suggesting a distinct "Japanese-type" mutation. In this paper, we report studies of 11 APRT-deficient lymphoblast cell lines. Nucleotide sequence analysis of APRT genomic DNA from WR2, a Japanese-type homozygote, identified a T to C substitution in exon 5, giving rise to the substitution of threonine for methionine at position 136. RNase mapping analysis confirmed this mutation in WR2 and revealed that six other Japanese-type homozygotes carry the same mutation on at least one allele. The remaining Japanese subject, who does not express the Japanese-type phenotype, did not demonstrate this mutation. Southern blot analysis showed that all seven Japanese-type subjects were confined to one TaqI restriction fragment length polymorphism (RFLP) haplotype. These studies provide direct evidence for the nature of the mutation in the Japanese-type APRT deficiency.
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PMID:Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. 334 50

A diet providing less than 20 mg of magnesium per 100 kcal that maintains urine pH near 6.0 3 to 5 hours after eating, or a diet providing this amount fo magnesium (see Table 2) with 1 gm of ammonium chloride or 1.5 gm of dl-methionine added daily, should be fed for 1 to 3 months to dissolve struvite uroliths (see Fig. 1). The low-magnesium diet should be fed indefinitely to prevent recurrence, because struvite urolithiasis and all of its effects (hematuria, pollakiuria, and/or complete to partial obstruction to urinary excretion) recurs repeatedly in cats that have previously experienced the condition if they are returned to regular cat food. In contrast, if a diet low in magnesium is fed, recurrence is uncommon. For cats that have never been affected, feeding a low-magnesium ration is unnecessary. For all cats, the following measures are recommended: encourage exercise, allow frequent urination, prevent obesity, decrease confinement, keep the litter box clean, and always have palatable water readily available.
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PMID:Treatment and prevention of feline struvite urolithiasis. 637 67

Diets supplemented with up to .6% DL-Met (DLM) or .68% 2-hydroxy-4-(methylthio)butanoic acid (HMB, Alimet) acidify the urine and reduce the incidence of urolithiasis in pullets and laying hens. Excessive acidification potentially may reduce eggshell quality and bone mineralization by interfering with Ca metabolism and may severely challenge the liver and kidneys, which are the primary organs responsible for attenuating metabolic acidosis. To evaluate these possibilities, 30-wk-old Single Comb White Leghorn hens in full production (five hens per replicate, six replicates per diet treatment) were fed for 30 d a 15.7% CP corn and soybean meal-based control layer ration alone or supplemented with DLM (.5, 1, 1.5, or 2%) or equimolar HMB (.56, 1.13, 1.69, or 2.25%). None of the diets caused mortality or gross hepatic or renal damage. Hens fed diets supplemented with the highest levels of DLM and HMB exhibited significant reductions in feed intake, hen-day egg production, and liver mass and had lower plasma concentrations of alanine amino-transferase and isocitrate dehydrogenase when compared with hens fed the control diet. Kidney mass was not significantly affected by high levels of DLM or HMB, but plasma uric acid was significantly higher in hens fed 2% DLM compared with hens fed the control diet. The highest levels of DLM and HMB did not significantly alter total plasma Ca or inorganic phosphate concentrations, nor were percentage eggshell or femur mineralization (femur ash mass:defatted bone mass, femur ash mass:bone volume) significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of laying hens to diets containing up to 2% DL-methionine or equimolar (2.25%) 2-hydroxy-4-(methylthio)butanoic acid. 814 73

To evaluate the possibility that kidney damage may be induced by the commercial practice of feeding high-Ca (HCa) prelayer rations, and to evaluate the protective efficacy of supplementing HCa diets with liquid methionine hydroxy analog free acid or DL-methionine, 12-wk-old female Single Comb White Leghorn pullets were fed one of the following corn-soybean meal-based diets until they reached 22 wk of age: normal-Ca (NC, 1% Ca); HCa (HC, 3.5% Ca); HCa supplemented with .34 or .68% liquid methionine hydroxy analog free acid (HC3A or HC6A); or HCa supplemented with .3 or .6% DL-methionine (HC3DL or HC6DL). The unsupplemented HC diet caused a significant reduction in kidney mass and a significant increase in the incidence of gross kidney damage and urolithiasis in pullets necropsied at 22 wk of age. Calcium-induced kidney damage was attenuated in a dose-response fashion by supplementing the HC diet with liquid methionine hydroxy analog and DL-methionine. None of the diets caused a significant metabolic acidosis. Plasma uric acid concentrations were not predictive of the extent of Ca-induced kidney damage. Analyses of glomerular size distributions indicated that subclinical or "hidden" kidney damage may not progressively develop into urolithiasis as hens mature. When compared with hens reared on the NC diet, rearing hens on the HC, HC3A, HC3DL, HC6A, or HC6DL diets did not consistently affect hen-day egg production, egg mass, eggshell mass, percentage eggshell, or bone mineralization.
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PMID:Liquid methionine hydroxy analog (free acid) and DL-methionine attenuate calcium-induced kidney damage in domestic fowl. 834 50

1. Susceptibility to calcium-induced urolithiasis was assessed in pullets of two commercial SCWL strains (A and B) reared together from 5 to 18 weeks of age on diets containing 10 g/kg calcium (normal calcium: NC) or 35 g/kg calcium (high calcium: HC). 2. Kidney damage was not observed in pullets reared on NC diets. For pullets fed on HC diets, strain A developed significantly greater kidney asymmetry, a higher incidence of gross kidney damage and a higher incidence of uroliths than strain B. 3. Supplementing the HC diet with 6 g/kg DL-methionine significantly reduced the incidence of calcium-induced gross kidney damage and urolith formation in both strains. Ammonium sulphate (5.3 g/kg) was significantly more effective than DL-methionine in reducing calcium-induced kidney damage. 4. Neither DL-methionine nor ammonium sulphate caused a measurable metabolic acidosis. Neither supplement consistently affected water consumption or manure moisture.
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PMID:Susceptibility of two commercial single comb White Leghorn strains to calcium-induced urolithiasis: efficacy of dietary supplementation with DL-methionine and ammonium sulphate. 835 42

Adenine phosphoribosyltransferase(APRT) deficiency is an autosomal recessive disorder and the homozygotes develop 2,8-dihydroxyadenine(DHA) urolithiasis and, in severe cases, renal failure. The prevalence is higher among the Japanese than other ethnic groups. So far 120 cases have been reported among the Japanese. The disease is classified into 2 types; type I and II are associated with complete and partial deficiencies, respectively. While all non-Japanese cases were of type I, about 78% of the Japanese patients were of type II. Each of the type II patients has at least one APRT*J allele with a ATG(Met) to ACG(Thr) base substitution at codon 136. All APRT*J alleles were derived from a single ancestor. All type I patients and some type II patients possess APRT*QO alleles with various point mutations or large gene abnormality. Type II patients tend to develop first symptoms later than the type I patients. The diagnoses of homozygotes and heterozygotes can be done by the cell culture methods. Both enzyme assay and molecular diagnostic methods are useful but not as reliable as the cell culture methods Excessive water intake, restriction of foods with high adenine contents and administration of allopurinol are useful treatments.
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PMID:[Adenine phosphoribosyltransferase(APRT) deficiency]. 897 13

Bacteria or their antigens persisting in the kidneys may induce the classical type of chronic pyelonephritis (CP), which progresses slowly, and may finally result in end-stage renal failure requiring dialysis. Pyelonephrogenic strains enter uro-epithelial and renal epithelial cells--where they accumulate--or may invade the renal interstitium. Promoting factors are obstruction, reflux, urolithiasis, nephrolithiasis, pregnancy, diabetes mellitus, humoral and cellular immunodeficiencies, immunosuppression treatment (e.g. following transplants), autoimmune phenomena (antigenic mimicry). Therapy comprises the treatment of underlying disease, antibiotics as indicated by the resistogram, acidification of urine (L-methionine), i.v. immunoglobulins (IgM, IgG) and oral vaccination with lyophilized uropathogens.
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PMID:[Chronic pyelonephritis. Synopsis of laboratory values and ultrasound lead to diagnosis]. 1090 12


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