Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

APRT deficiency is an enzyme disorder which is inherited as an autosomal recessive trait. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised by xanthine oxidase to poorly insoluble 2, 8-dihydroxyadenine (DHA). The dihydroxyadenine forms stones which cause recurrent urolithiasis, frequent episodes of urinary tract infection or interstitial nephritis, and finally renal insufficiency in some cases. We report a case of APRT deficiency discovered by urine examination. The patient was a 33-year-old man who had never had any episodes of urolithiasis. He was admitted to our hospital because of pseudoarthrosis of his left arm caused by a traffic accident. His urinalysis revealed no proteinuria nor hematuria, but disclosed numerous round brown crystals in the sediment. These crystals had the characteristics of 2, 8-DHA. The enzyme activity of APRT in his blood was completely deficient. He was diagnosed as an APRT* QO homozygote. In addition, diagnostic imaging revealed that his right kidney was poorly hypoplastic and the pelvis of his left kidney was extra-renal. The renal function was slightly disturbed. In Japan 6 cases of 2, 8-DHA urolithiasis associated with hypoplastic kidney had been reported by 1989. Theoretically, the incidence of hypoplastic kidney is around 20% of all 2, 8-DHA urolithiasis cases. We suspect a genetic correlation between hypoplastic kidney and APRT deficiency. This patient was treated with Allopurinol, which inhibits the process of xanthine oxidation, after which crystals were no longer detected in his urine.
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PMID:[A case of adenine phosphoribosyltransferase (APRT) deficiency discovered by urine examination]. 781 52

Deficiencies in different steps of purine metabolism give rise to a number of human inherited disorders. Lesch-Nyhan syndrome is a severe neurological disorder, caused by a deficiency in the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). HPRT-deficient mice have been generated, but have proved to be an unsuccessful model of the human disease. We have suggested that this may be due to a greater dependency in rodents on the other purine salvage enzyme, adenine phosphoribosyltransferase (APRT). We have generated an APRT-deficient mouse line by gene targeting, with a phenotype that closely resembled the symptoms of APRT deficiency in man. APRT null mice were viable, but 90% died prematurely before 6 months of age, displaying highly abnormal kidney morphology, with pathology characteristic of tubule obstruction. These mice have elevated urinary levels of adenine and 2,8-dihydroxyadenine, a highly insoluble adenine derivative, plus birefringent crystalline deposits and calculi within tubules throughout the kidney. A standard therapy for APRT-deficient human patients is the administration of the xanthine oxidase inhibitor, allopurinol. This has proved an effective therapy for APRT null mice, preventing accumulation of 2,8-dihydroxyadenine and much of the resultant renal obstruction, allowing us to establish a breeding line. We believe that these mice should provide a useful model for further study of APRT deficiency in humans. Furthermore, by generating APRT and HPRT double mutants, we will be able to test our hypothesis that both genes must be inactivated in mice before a model for Lesch-Nyhan syndrome can be obtained.
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PMID:Mice with adenine phosphoribosyltransferase deficiency develop fatal 2,8-dihydroxyadenine lithiasis. 886 50

Adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency is an enzymopathy of purine metabolism, which is inherited as an autosomal recessive trait. APRT is a salvage enzyme that normally catalyzes the conversion of adenine to adenosine monophosphate. APRT deficiency results in adenine accumulation with oxidation by xanthine dehydrogenase (XDH; EC 1.1.1.204) to 2,8-dihydroxyadenine (2,8-DHA) then excreted in urine. This compound is extremely insoluble and its crystallization can lead to stone formation and renal failure. The diagnosis of the disease is based on stone analysis by infrared spectroscopy or microscopic examination of urine, which may reveal typical 2,8-DHA crystals. The enzyme activity measurements in erythrocyte lysates will identify both homozygotes and heterozygotes for APRT deficiency. Molecular approach can identify mutations which are responsible of this inherited disease. Two types of deficit are commonly distinguished, depending on the level of residual APRT activity: type I, mainly observed in Caucasian subjects, in whom the enzyme activity is undetectable in homozygous patients and type II, found in Japanese patients who are able to form APRT but the enzyme activity is strikingly reduced because a low affinity for phosphoribosylpyrophosphate. The crystallization of 2,8-DHA and subsequent renal damages may be prevented with allopurinol therapy, a xanthine oxidase inhibitor. The role of the laboratory is crucial to detect APRT deficiency and to assess the efficacy of therapy, the objective being to avoid 2,8-DHA crystal formation.
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PMID:[2,8-dihydroxyadenine nephrolithiasis: from diagnosis to therapy]. 1803 2

Adenine phosphoribosyltransferase deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. The stones are characteristically radiolucent. 2, 8-Dihydroxyadenine (2, 8-DHA) formation is blocked by xanthine oxidase blocker allopurinol. Here, we report the case of an eight-month-old baby girl who presented with obstructive acute kidney injury secondary to calculi which was treated with surgical removal of stone. The analysis of the calculi revealed 2, 8-DHA crystals.
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PMID:Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease. 3124 41

Adenine phosphororibosyl transferase (APRT) deficiency, a rare inborn error of metabolism is inherited as an autosomal recessive trait. It presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy and recurrent nephrolithiasis and often progresses to end stage renal disease (ESRD). After transplant, it can recur in the allograft. If APRT deficiency is recognized early, renal failure can be prevented, arrested or reversed in native kidney and in allograft by treatment with allopurinol, which inhibits xanthine oxidase and reduces 2,8-DHA formation. We report two cases of APRT deficiency from our center. DNA sequencing of APRT gene performed in one of the cases revealed a pathogenic variant in Exon1 of APRT gene (c.3G>C; p.Met1). This variant affects the translation initiation codon and results in a start loss. The variant has previously been reported in two cases with APRT deficiency.
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PMID:Crystalline Nephropathy due to APRT Deficiency: A Preventable Cause of Renal and Renal Allograft Failure. 3327 97