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

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

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