Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We report a case of 2, 8-dihydroxyadenine (2, 8-DHA) urolithiasis. A 39-year-old female was referred to our hospital with the complaint of right flank pain. An X-ray examination showed right hydronephrosis. On May 1986, right percutaneous nephrolithotripsy was performed. Infrared spectroanalysis revealed 2, 8-DHA and calcium phosphate mixed calculus. The adenine phosphoribosyltransferase activity in erythrocytes was partially deficient. Since the operation, 300 mg/day of allopurinol has been administered, and there have been no signs of recurrence.
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PMID:[A case of 2,8-dihydroxyadenine stones with a partial deficiency of adenine phosphoribosyltransferase]. 304 75

We report the first patient in Finland and Scandinavia with a deficiency of adenine phosphoribosyltransferase (APRT). About 30 clinically affected patients have been reported in the literature. APRT deficiency is an enzyme disorder which is inherited autosomally in a recessive manner. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised to poorly insoluble 2,8-dihydroxyadenine by xanthine oxidase. The dihydroxyadenine forms stones which can be mistaken for uric acid stones. Our patient had had frequent episodes of urolithiasis and the diagnosis was finally made after pyelolithotomy and stone analysis. The total APRT deficiency was detected in the haemolysate of erythrocytes. Partial deficiency of APRT in the patient's relatives showed heterozygosity of the enzyme defect. The only clinical manifestation of the defect is the formation of urinary stones. This can be prevented by diet and allopurinol.
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PMID:Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine urolithiasis in a 48-year-old woman. 280 78

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

Patients with 2,8-dihydroxyadenine urolithiasis are either completely or partially deficient in adenine phosphoribosyltransferase activities. Patients with partial enzyme deficiencies, all of whom have been found among Japanese, are homozygotes having a unique mutant adenine phosphoribosyltransferase gene (APRT*J) in double dose (Japanese type deficiency). We have established B-cell lines from heterozygotes and homozygotes of complete and Japanese type adenine phosphoribosyltransferase deficiencies as well as normal individuals. Characterization of the cell lines indicated that all homozygous cells were deficient in adenine phosphoribosyltransferase function while all heterozygous and normal cells had functional adenine phosphoribosyltransferase.
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PMID:Establishment and characterization of B cell lines from individuals with various types of adenine phosphoribosyltransferase deficiencies. 348 62

In one case of 2,8-dihydroxyadenine urolithiasis, reduced adenine phosphoribosyltransferase activity was found. The patient's enzyme had normal affinity for adenine but reduced affinity for substrate phosphoribosyl-pyrophosphate. It was much more stable at 60 degrees C than control. It seems that erythrocyte adenine phosphoribosyltransferase obtained from the patient may be a variant enzyme.
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PMID:A mutant adenine phosphoribosyltransferase in 2,8-dihydroxyadenine urolithiasis. 376 54

2,8-Dihydroxyadeninuria is a rare purine metabolic disorder that has been reported to have caused urolithiasis in 14 cases, mostly children. Excretion of the hydroxylated metabolites of adenine results from a deficiency of adenine phosphoribosyltransferase. The insoluble calculi have a similar chemical structure to uric acid and frequently are misdiagnosed as uric acid calculi. Management differs from that of uric acid urolithiasis. We report on an adult with 2,8-dihydroxyadenine urolithiasis in the United States.
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PMID:2,8-Dihydroxyadenine urolithiasis: report of an adult case in the United States. 380 29


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