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)

A 48-year-old man with a history of recurrent urolithiasis and chronic renal failure underwent a nephrectomy for a renal mass. At surgery the mass proved to be a calculus impacted in a dilated calyx. Gross examination of the kidney revealed chalky white deposits in the deep medulla and papillary tips. Histologic examination revealed chronic interstitial nephritis with brown spicules within some tubular epithelial cells and larger deposits of brown crystals within tubular lumina, the interstitium of the medulla, and papillary tips. Polarization microscopy revealed individual crystals scattered throughout the renal parenchyma. Although the arrangement of the crystals was reminiscent of uric acid, and, in fact, a clinical diagnosis of gouty nephropathy was made, x-ray diffraction analysis demonstrated crystals of 2,8-dihydroxyadenine. Enzymatic studies confirmed the complete absence of adenine phosphoribosyltransferase activity in erythrocyte lysates.
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PMID:Renal insufficiency secondary to 2,8-dihydroxyadenine urolithiasis. 151 30

A novel method for measuring AMP-deaminase activity in human erythrocytes is presented, based on the determination of the reaction product, IMP, using high performance liquid chromatography. IMP formation was found to be proportional both to the incubation time and the amount of haemolysate over a wide range. The minimal detectable AMP-deaminase activity was more than 1000 times lower than the mean activity found in healthy controls (1083 nmol/h/mg Hb). No marked difference of activity was found in the patients with the following inherited purine disorders: familial juvenile gouty nephropathy and deficiencies of adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase or adenine phosphoribosyltransferase. The activity in the erythrocytes of patients with chronic renal failure was also similar to controls. The existence of subjects with low erythrocyte AMP-deaminase activity in the population has been confirmed.
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PMID:A high performance liquid chromatographic assay for AMP-deaminase activity in the erythrocytes of healthy subjects and patients with inherited purine disorders. 191 25

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

We report a case of adenine phosphoribosyltransferase deficiency in which the initial presentation was chronic renal failure. Diagnosis was made after infrared microscopy analysis of microcrystalline deposits on a kidney allograft biopsy specimen. This type of presentation is rarely seen, the most frequent manifestation of this disease being urolithiasis. This is the first report of recurrence of the microcrystalline nephritis in a kidney transplant with subsequent loss of allograft function.
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PMID:Chronic renal failure secondary to 2,8-dihydroxyadenine deposition: the first report of recurrence in a kidney transplant. 802 15

Homozygous adenine phosphoribosyltransferase deficiency is a genetic defect that is associated with 2,8-dihydroxyadenine urolithiasis. Since the prevalence of the heterozygous state is found in 0.4% to 1.2% of the population, it is surprising that more cases of 2,8-dihydroxyadenine urolithiasis have not been reported. Herein we describe a patient with complete adenine phosphoribosyltransferase deficiency with 2,8-dihydroxyadenine urolithiasis leading to chronic renal failure. Gene sequencing revealed that the patient is a compound heterozygote. One of the mutations (a T insertion between bases 346 and 347) has been encountered before, but the second (a G-to-A substitution at base 1356) has not been previously reported. Possible explanations for the unexpected rarity of 2,8-dihydroxyadenine urolithiasis are discussed.
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PMID:Adenine phosphoribosyltransferase deficiency with renal deposition of 2,8-dihydroxyadenine leading to nephrolithiasis and chronic renal failure. 844 14

The presence of crystal deposits in tissues is associated with various pathologies. Sometimes their identification is useful for understanding the etiology or the mechanism of the disorder. The authors applied Fourier transform infrared microscopy (FTIRM) to the molecular characterization of crystal deposits in tissue and compared the results with those provided by histologic studies using polarized light microscope and histochemical reactions. Twenty-five biopsies were investigated. In 10 cases, the results were in good agreement. In 15 cases only FTIRM could precisely identify the crystals. In three cases, this technique allowed to characterize dihydroxyadenine crystals revealing an adenine phosphoribosyltransferase deficiency previously undiagnosed in patients presenting severe chronic renal failure. In three cases, crystal deposition was related to drug therapy. In other cases, crystal identification was useful to understand the mechanism of the pathology responsible for tissue damage and crystal deposition.
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PMID:Fourier transform infrared microscopy identification of crystal deposits in tissues: clinical importance in various pathologies. 862 66

In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. Treatment with allopurinol controls formation of DHA stones by inhibiting XDH activity. Kidney disease in APRT-deficient mice resembles that seen in humans. By age 12 wk, APRT-deficient male mice are, on average, mildly anemic and smaller than normal males. They have extensive renal interstitial damage (assessed by image analysis) and elevated blood urea nitrogen (BUN), and their creatinine clearance rates, which measure excretion of infused creatinine as an estimate of glomerular filtration rate (GFR), are about half that of wild-type males. APRT-deficient males treated with allopurinol in the drinking water had normal BUN and less extensive visible renal damage, but creatinine clearance remained low. Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.
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PMID:Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency. 968 17

In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is present in all tissues and provides the only known mechanism for the metabolic salvage of adenine resulting from the polyamine biosynthesis pathway or from dietary sources. In humans, APRT deficiency results in serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA) precipitation in the renal interstitium. To address the molecular basis of DHA-urolithiasis, the recombinant human APRT was crystallized in complex with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction data extended to 2.1 A resolution led to a final crystallographic R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of nine beta-strands and six alpha-helices, and the active site pocket opens slightly to accommodate the AMP product. The core of APRT is similar to that of other phosphoribosyltransferases (PRTases), although the adenine-binding domain is quite different. Structural comparisons between the human APRT and other "type I" PRTases of known structure revealed several important features of the biochemistry of PRTases. We propose that the residues located at positions corresponding to Leu159 and Ala131 in hAPRT are responsible for the base specificities of type I PRTases. The comparative analysis shown here also provides structural information for the mechanism by which mutations in the human APRT lead to DHA-urolithiasis.
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PMID:Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis. 1519 8