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)

An accurate diagnosis of heterozygotes for autosomal recessive disorders with unknown mutations can be difficult. Using a unique phenomenon occurring in vivo, we designed a method for the diagnosis of heterozygotes for adenine phosphoribosyltransferase (APRT) deficiency which makes way for a qualitative distinction between normal and heterozygous subjects. We cultured peripheral blood mononuclear cells with 2,6-diaminopurine, an APRT-dependent cytotoxin, to search for in vivo mutational cells. Fifteen putative heterozygotes examined were found to possess such mutant cells at rather high frequencies; thus, a false negative diagnosis is unlikely. The analysis of genomic DNA in 82 resistant clones from two of the heterozygotes clarified that 64 (78%) had lost the germinally intact alleles. Thirteen members of APRT-deficient families were examined; eight proved to be heterozygotes. Among 425 individuals from two separate residential areas of Japan, two heterozygotes were found. The authenticity of the heterozygosity was validated by two separate methods for the two heterozygotes; hence, a false positive diagnosis can be ruled out. Our data showed a calculated heterozygote frequency of 0.47% (95% confidence limits; 0.05%-1.7%), a value compatible with that (1.2%) calculated from data concerning the incidence of 2,8-dihydroxyadenine urolithiasis. This novel genetic approach for identifying heterozygotes is now being tested to search for other enzyme deficiencies in humans.
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PMID:Diagnosis of heterozygous states for adenine phosphoribosyltransferase deficiency based on detection of in vivo somatic mutants in blood T cells: application to screening of heterozygotes. 199 41

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

To the now 17 case reports in caucasian patients of an urolithiasis in a rare purine metabolism disorder 2,8-dihydroxyadeninuria due to missing activity of adenine phosphoribosyltransferase 3 further cases are presented. Firstly, a monozygotic twin pair is afflicted (13-year-old boys). All calculi be composed of pure 2,8-DHA, except a mixed calculus in a 38-year-old man containing of 80% 2,8-DHA and 20% calcium oxalate. The actual literature is reviewed.
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PMID:[Urolithiasis in 2,8-dihydroxyadeninuria: presentation of 3 additional cases]. 223 80

We report a case of acquired idiopathic sideroblastic anemia associated with adenine phosphoribosyltransferase (APRT) deficiency. A 72-year-old male had been troubled with urolithiasis since his teens. In 1984, he was referred to us because of chronic renal failure and anemia. He was diagnosed as having sideroblastic anemia and required red cells transfusion regularly. In June 1989, he was admitted to our hospital because of cerebral infarction. Peripheral blood analysis showed pancytopenia. Bone marrow aspiration revealed hypercellularity with 36.2% erythroblasts, and 18.5% ringed sideroblasts of all nucleated cells. According to the FAB classification, a diagnosis of refractory anemia with ring sideroblasts was made. As his urinary stone consisted of 2, 8-dihydroxyadenine by analysis of infrared spectrum, genetic and enzymatic studies were performed. These studies indicated APRT deficiency. He died of pneumonia accompanied with progressive renal failure on August 9, 1989.
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PMID:[Sideroblastic anemia associated with adenine phosphoribosyltransferase deficiency]. 225 60

Inherited adenine phosphoribosyltransferase (APRT) has a recessive transmission. When it is very important, adenine can't be restored into nucleic acids pool and will changed into 2,8-dihydroxyadenine (2,8-DHA) by xanthine oxidase. To date in all countries but Japan, 2,8-DHA urolithiasis is observed only into homozygotic subjects with complete APRT deficiency Commonly, its onset is observed in childhood often dramatically. The authors report two new pediatric cases into new french families. First a 8 years old boy with spontaneous elimination of two lithiasis after right lumbar pain. Secondly an infant (nineteen months) who has presented an acute renal failure with anuria. Bilateral lithiasis included into pyelourectal junctions have been pulled out by bilateral surgical pyelotomy. In each case, lithiasis were radiolucent and diagnosis made by ultrasonography. The uric acid metabolism was normal and it is the infra red spectrophotometric study of stones that had recognised the 2,8-DHA component. In the second case, bilateral residual lithiasis have been broken by piezoelectric extra-corporeal lithotripsy with good tolerance and favorable result. The two children received preventive treatment. After 36 and 19 months they have no recurrence. In the literature, the frequency of 2,8-DHA lithiasis is very more low than the theoretical of homozygotics in population (1/100,000). The common confusion with uric lithiasis is one possible explanation. So spectrophotometric study of radiolucent stones was meant to be realised when uric metabolism is not disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[2,8-dihydroxyadenine lithiasis. 2 new pediatric cases of an unknown metabolic deficit. The use of extracorporal lithotripsy]. 238

Three siblings in a Japanese family experienced recurrent 2,8-dihydroxyadenine urolithiasis despite the presence of adenine phosphoribosyltransferase (APRT) activities in the hemolysates (19.9% to 28.2% of normal value). However, studies on viable T cells from these patients indicated that APRT was not functional in viable cells. Further analysis of the partially purified enzymes from hemolysates disclosed that patient's APRT had a reduced affinity to 5-phosphoribosyl-1-pyrophosphate (PRPP). Seven healthy members of this family whose APRT functioned normally in viable T cells had the erythrocyte enzyme levels between the patients and normal individuals (38.2% to 65.6%), suggesting that they are carriers of the defective gene. These results indicate that the defective gene code a unique mutant APRT with a reduced affinity to PRPP, and the patients are homozygotes. The mutant enzyme was also shown to be more heat-stable than normal enzyme. However, since mutant enzyme, unlike normal enzyme, was insensitive to the stabilization effect of PRPP, the latter became more heat-stable than the former when the heat treatment was performed in the presence of PRPP. This type of defect with alterations in the kinetic and physical properties of APRT as described here is likely to be a common type of APRT deficiency in Japan.
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PMID:Altered kinetic properties of a mutant adenine phosphoribosyltransferase. 241 31

We have studied adenine phosphoribosyltransferase (APRT) in the hemolysates from the families of 2,8-dihydroxyadenine urolithiasis associated with partial deficiency of APRT (the Japanese type) and complete deficiency of APRT (the null type). The APRT in the control subjects was found to be heat-stable at the physiological concentration of phosphoribosylpyrophosphate (PRPP), which was close to the value of its Km for PRPP. The APRT in the Japanese type showed 10 times higher Km values for PRPP and needed a comparably increased level of PRPP for stability in vitro. No change in red cell PRPP was found in the Japanese type of APRT deficiency. The content of APRT enzyme protein was decreased in the hemolysates of the Japanese type, probably due to its lability at the level of PRPP present in the cells. The heterozygote of the null type also had labile enzyme molecules at the physiological PRPP concentration.
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PMID:Partial and complete adenine phosphoribosyltransferase deficiency associated with 2,8-dihydroxyadenine urolithiasis: kinetic and immunochemical properties of APRT. 244 Jun 71

Inherited adenine phosphoribosyltransferase (APRT) has a recessive transmission. When it is very important, adenine can't be restored into nucleic acids pool and will changed into 2,8-dihydroxyadenine (2,8-DHA) by xanthine oxydase. To date in all countries but Japan, 2,8-DHA urolithiasis is observed only into homozygotic subjects with complete APRT deficiency. Commonly, its onset is observed in childhood often dramatically. The authors report two new pediatric cases in two new french families. First a 8 year old boy with spontaneous elimination of two lithiasis after right lumbar pain. Secondly an infant (nineteen months) who has presented an acute renal failure with anuria. Bilateral lithiasis incluted into pyeloureteral junctions have been pulled out by bilateral surgical pyelotomy. In each case, lithiasis were radioluscent and diagnosis made by ultrasonography. The uric acid metabolism was normal and it is the infra red spectrophotometric study of stones that had recogniseed the 2,8-DHA component. In the second case, bilateral residual lithiasis have been broken by piezoelectric extracorporeal lithotrypsy with good tolerance and favorable result. The two children received permanent preventive treatment. After 36 and 19 months they have no recurrence. In the literature, the frequency of 2,8-DHA lithiasis is very more low than the theorical incidence of homozygotics in population (1/100,000). The common confusion with uric lithiasis is one possible explanation. So spectorophotometric study of radioluscent stones was meant to be realised when uric metabolism is not disturbed. Prevention associates alimentary diet without purins and permanent treatment by allopurinol (10 mg/kg/day in a child). Not used to date, piezo-electric extracorporeal lithotrypsy seems to take a place for treatment of initial, residual or recurrent 2,8-DHA lithiasis like for our young patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[2,8-dihydroxyadenine lithiasis. 2 new pediatric cases of this misdiagnosed metabolic abnormality. The value of extracorporeal lithotripsy]. 269 87

Disorders of purine metabolism are well recognized clinical entities in modern medical practice. However, there are lesser known aberrations of purine and pyrimidine metabolism that can manifest as disease states. Deficiency of the enzyme adenine phosphoribosyltransferase is an autosomal recessive inherited disorder resulting in 2,8-dihydroxyadenuria, and possible urolithiasis and renal insufficiency. A woman with a pure 2,8-dihydroxyadenine ureteral calculus is reported, who represents the third reported case in the United States. Stones comprised of 2,8-dihydroxyadenine are difficult to distinguish from uric acid clinically, making sophisticated crystallographic analysis essential for accurate diagnosis. Treatment differs from that appropriate for uric acid lithiasis due to the limited solubility of 2,8-dihydroxyadenine at pH levels of less than 9. Prevention requires purine restriction and allopurinol.
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PMID:2,8-Dihydroxyadenine urolithiasis: report of a case in a woman in the United States. 274 54


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