Adenine Phosphoribosyltransferase Research Articles

Cr-induced changes in leaf protein profile, ultrastructure and photosynthetic traits in the two contrasting tobacco genotypes

Soil Cr contamination has emerged as an increasing problem worldwide. To investigate the genotypic difference on the effect of Cr in tobacco, Hydroponic experiments were performed, assessing changes in proteomes, transcriptional features as well as the ultrastructure and photosynthetic characteristics of two contrasting tobacco genotypes Guiyan 1 (Cr-tolerant) and Yunyan 2 (Cr-sensitive) under Cr exposure. Transmission electron microscopy observation depicted that Guiyan 1 was less influenced by Cr stress than Yunyan 2. Leaves of Guiyan 1 exhibited relatively well composed arrangement of photosynthetic apparatus as compared with that of Yunyan 2. A total of 86/74 and 107/77 proteins showed more-/less-abundance following Cr treatment in Guiyan 1 and Yunyan 2. Twelve Cr-tolerance-associated proteins were identified, using two-dimensional gel electrophoresis coupled with mass spectrometry, whose expressions were significantly induced in Guiyan 1 leaves but down-regulated/unchanged in Yunyan 2, or unchanged in Guiyan 1 but down-regulated in Yunyan 2 under 100 µM Cr stress. They are including mitochondrial processing peptidase, dehydrin, superoxide dismutase, adenine phosphoribosyl transferase, mitochondrial malate dehydrogenase proteins. Based upon their functions, they are categorized in four groups: stress response, energy, RNA-binding and metabolism related proteins. Furthermore, the expression patterns of four Cr-responsive proteins were validated by quantitative real-time PCR. The data extend our knowledge to understand the underlying Cr tolerance mechanisms and provide an insight into possible utilization of elite genetic resources for the development of Cr tolerant tobacco genotypes.

Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR)

5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects.

E36 Clinical presentation of unusual purine urolithiasis: hereditary xanthinuria and adenine phosphoribosyltransferase deficiency

E36 Clinical presentation of unusual purine urolithiasis: hereditary xanthinuria and adenine phosphoribosyltransferase deficiency

Efficient one-pot synthesis, molecular docking and in silico ADME prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents.

Bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4-hydroxycoumarin and substituted aromatic aldehydes using succinimide-N-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of Leishmania donovani. Compounds 3a (IC50= 155 μg/mL), 3g (IC50= 157.5 μg/mL) and 3l (IC50= 150 μg/mL) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50= 490 μg/mL). Also, synthesized compounds 3(a-l) did not show cytotoxicity against HeLa cell line upto tested concentrations. Further, molecular docking study against Adenine phosphoribosyltransferase of Leishmania donovani showed good binding interactions. ADME properties were analyzed and showed good oral drug candidate like properties. The synthesized compounds were also shown good drug likeness and drug score values when compared with drugs currently used in therapy. The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.

Determination of Activity of the Enzymes Hypoxanthine Phosphoribosyl Transferase (HPRT) and Adenine Phosphoribosyl Transferase (APRT) in Blood Spots on Filter Paper.

Hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency is the cause of Lesch-Nyhan disease. Adenine phosphoribosyl-transferase (APRT) deficiency causes renal calculi. The activity of each enzyme is readily determined on spots of whole blood on filter paper. This unit describes a method for detecting deficiencies of HPRT and APRT.

Use of LightCycler mutation analysis to detect type II adenine phosphoribosyltransferase deficiency in two patients with 2,8-dihydroxyadeninuria.

Recently, a number of methods have been devised for detection of mutations in the field of molecular genetics. The LightCycler system has been used for rapid PCR, while simultaneously quantifying and analyzing the amplification results. We tried to apply the LightCycler system to detect APRT*J allele mutations in two families including two children with 2,8-dihydroxyadenine urolithiasis. The first patient was a 3-year-old girl who presented with left flank pain. The second patient was a 2-year-old girl who presented with complaints of sudden dysuria. The spectrophotometric analysis of the stone fragments of both patients revealed an absorption spectrum for 2,8-DHA. We used the LightCycler system to detect APRT*J mutation. The first patient was homozygous for APRT*J/APRT*J and the second patient was compound heterozygous for APRT*J/APRT*Q0. The genetic diagnosis of APRT deficiency using this system may be useful not only as a diagnostic test for infants with known 2,8-DHA, but also as a screening of infants with a suspicion of urolithiasis. We believed that the LightCycler system still is an important means of identifying APRT*J mutation.

Purine metabolism gene deregulation in Parkinson's disease.

To explore alterations in the expression of genes encoding enzymes involved in purine metabolism in Parkinson's disease (PD) brains as purines are the core of the DNA, RNA, nucleosides and nucleotides which participate in a wide variety of crucial metabolic pathways. Analysis of mRNA using real-time quantitative PCR of 22 genes involved in purine metabolism in the substantia nigra, putamen and cerebral cortex area 8 in PD at different stages of disease progression, and localization of selected purine metabolism-related enzymes with immunohistochemistry. Reduced expression of adenylate kinase 2 (AKA2), AK3, AK4, adenine phosphoribosyltransferase, ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), ENTPD3, nonmetastatic cells 3, nucleoside-diphosphatese kinase 3 (NME1), NME7 and purine nucleoside phosphorylase 1 (PNP1) mRNA in the substantia nigra at stages 3-6; up-regulation of ADA mRNA in the frontal cortex area 8 at stages 3-4 and of AK1, AK5, NME4, NME5, NME6, 5'-nucleotidase (NT5E), PNP1 and prune homolog Drosophila at stages 5-6. There is no modification in the expression of these genes in the putamen at stages 3-5. Gene down-regulation in the substantia nigra may be interpreted as a consequence of dopaminergic cell death as ENTPD3, NME1, NME7, AK1 and PNP1 are mainly expressed in neurons. Yet ENTPD1 and NT5E, also down-regulated in the substantia nigra, are expressed in astrocytes, probably pericytes and microglia, respectively. In contrast, gene up-regulation in the frontal cortex area 8 at advanced stages of the disease suggests a primary manifestation or a compensation of altered purine metabolism in this region.

Effect of Caffeine on the Expression Pattern of Water-Soluble Proteins in Rice (Oryza sativa) Seedlings

It has been suggested that caffeine acts as an allelochemical which influences the germination and growth of plants. The effect of caffeine on the expression profiles of proteins was investigated in shoot-root axes of rice (Oryza sativa) seedlings. Two-dimensional difference gel electrophoresis combined with Matrix-Assisted Laser Desorption/Ionization Time of Flight/Time of Flight Mass Spectrometry was employed for the separation and identification of proteins. The results indicated that amounts of 51 protein spots were reduced and 14 were increased by treatment with 1 mM caffeine. Twelve rice seedling proteins were identified. Down-regulated proteins were β-tubulin, sucrose synthase, glyceraldehyde-3-phosphate dehydrogenase, reversibly glycosylated polypeptide/α-1,4-glucan protein synthase and cytoplasmic malate dehydrogenase. In contrast, up-regulated proteins were alanyl-aminopeptidase, acetyl-CoA carboxylase, adenine phosphoribosyltransferase, NAD-malate dehydrogenase, ornithine carbamoyltransferase, glucose-6-phosphate isomerase and nuclear RNA binding protein. Possible alternation of metabolism caused by caffeine is discussed with the protein expression data.

Adenine phosphoribosyltransferase from Sulfolobus solfataricus is an enzyme with unusual kinetic properties and a crystal structure that suggests it evolved from a 6-oxopurine phosphoribosyltransferase.

The adenine phosphoribosyltransferase (APRTase) encoded by the open reading frame SSO2342 of Sulfolobus solfataricus P2 was subjected to crystallographic, kinetic, and ligand binding analyses. The enzyme forms dimers in solution and in the crystals, and binds one molecule of the reactants 5-phosphoribosyl-α-1-pyrophosphate (PRPP) and adenine or the product adenosine monophosphate (AMP) or the inhibitor adenosine diphosphate (ADP) in each active site. The individual subunit adopts an overall structure that resembles a 6-oxopurine phosphoribosyltransferase (PRTase) more than known APRTases implying that APRT functionality in Crenarchaeotae has its evolutionary origin in this family of PRTases. Only the N-terminal two-thirds of the polypeptide chain folds as a traditional type I PRTase with a five-stranded β-sheet surrounded by helices. The C-terminal third adopts an unusual three-helix bundle structure that together with the nucleobase-binding loop undergoes a conformational change upon binding of adenine and phosphate resulting in a slight contraction of the active site. The inhibitor ADP binds like the product AMP with both the α- and β-phosphates occupying the 5'-phosphoribosyl binding site. The enzyme shows activity over a wide pH range, and the kinetic and ligand binding properties depend on both pH and the presence/absence of phosphate in the buffers. A slow hydrolysis of PRPP to ribose 5-phosphate and pyrophosphate, catalyzed by the enzyme, may be facilitated by elements in the C-terminal three-helix bundle part of the protein.

Recurrence of crystalline nephropathy after kidney transplantation in APRT deficiency and primary hyperoxaluria.

Purpose of reviewTo provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients.Source of informationPubmed literature search.SettingPrimary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation.Key messagesPatients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non-responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m2; in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation.LimitationsThe availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients.ImplicationsIncreasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation.

Rare Radiolucent Hydroxyadenine Renal Stones in 4 Years Old Boy

Adenine phosphoribosyltransferase (APRT) deficiency is a rare under-recognized disorder of adenine metabolism. It has a familial tendency and is inherited as autosomal recessive. APRT deficiency eventually leads to increased production of 2,8-dihydroxyadenine (DHA) which has a low solubility at normal range of urine PH resulting in the formation of DHA crystals and recurrent kidney stones as the main presenting feature [1]. Deposition of Dihydroxyadenine crystals in the renal tubules can lead to permanent renal damage with significant morbidity.

Recurrent 2,8-Dihydroxyadenine Nephropathy: A Rare but Preventable Cause of Renal Allograft Failure

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n = 2), acute-on-chronic (n = 5) or acute (n = 1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n = 7), remained stable (n = 1) or worsened (n = 1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.

METABOLISM OF PURINE NUCLEOSIDES AND BASES IN SUSPENSION-CULTURED ARABIDOPSIS THALIANA CELLS

We study the metabolism of purine nucleosides and purine bases in suspension-cultured cells of the model plant Arabidopsis thaliana . [8- 14 C]Adenosine, [8- 14 C]guanosine, [8- 14 C]inosine, [8- 14 C]xanthosine, [8- 14 C]adenine, [8- 14 C]guanine, [8- 14 C]hypoxanthine and [8- 14 C]xanthine were administered to cells in the cell division phase, and the uptake and metabolic fate of these compounds were monitored for 4h. The rates of uptake of most purines were within the range 60-70 nmol/gFW. Xanthine and xanthosine were taken up more slowly. The rate of uptake was ordered as hypoxanthine > adenine > inosine > guanosine > guanine > adenosine > xanthosine> xanthine. A large amount of radioactivity from [8- 14 C]adenosine, [8- 14 C]guanosine, [8- 14 C]adenine and [8- 14 C]guanine, and a limited amount from [8- 14 C]inosine and [8- 14 C]hypoxanthine, was incorporated into nucleotides and RNA. The so-called purine salvage pathways of adenosine, guanosine, adenine, guanine, inosine and hypoxanthine are therefore functional in A. thaliana . These tracer experiments also reveal that significant amounts of these compounds were converted to xanthine, and enter the catabolic pathway via allantoin. Neither xanthosine nor xanthine is used in the synthesis of nucleotides and RNA. These compounds are entirely catabolized via allantoin and allantoic acid. Deamination of adenine and guanine rings takes place at the stage of AMP deaminase and guanosine deaminase, respectively. The pattern of purine metabolism in A. thaliana is similar to that in other plants. Adenine salvage activity estimated from the metabolism of [8- 14 C]adenine, the cellular concentration of ATP, and expression of the APT1 gene encoding adenine phosphoribosyltransferase all increased markedly at the lag phase of cell proliferation . These observations imply that the salvage pathway is important during the early stages of cell culture in A. thaliana .

Toward stable gene expression in CHO cells

Maintaining high gene expression level during long-term culture is critical when producing therapeutic recombinant proteins using mammalian cells. Transcriptional silencing of promoters, most likely due to epigenetic events such as DNA methylation and histone modifications, is one of the major mechanisms causing production instability. Previous studies demonstrated that the core CpG island element (IE) from the hamster adenine phosphoribosyltransferase gene is effective to prevent DNA methylation. We generated one set of modified human cytomegalovirus (hCMV) promoters by insertion of one or two copies of IE in either forward or reverse orientations into different locations of the hCMV promoter. The modified hCMV with one copy of IE inserted between the hCMV enhancer and core promoter in reverse orientation (MR1) was most effective at enhancing expression stability in CHO cells without comprising expression level when compared with the wild type hCMV. We also found that insertion of IE into a chimeric murine CMV (mCMV) enhancer and human elongation factor-1α core (hEF) promoter in reverse orientation did not enhance expression stability, indicating that the effect of IE on expression stability is possibly promoter specific.

Inborn errors of purine metabolism: clinical update and therapies

Inborn errors of purine metabolism exhibit broad neurological, immunological, haematological and renal manifestations. Limited awareness of the phenotypic spectrum, the recent descriptions of newer disorders and considerable genetic heterogeneity, have contributed to long diagnostic odysseys for affected individuals. These enzymes are widely but not ubiquitously distributed in human tissues and are crucial for synthesis of essential nucleotides, such as ATP, which form the basis of DNA and RNA, oxidative phosphorylation, signal transduction and a range of molecular synthetic processes. Depletion of nucleotides or accumulation of toxic intermediates contributes to the pathogenesis of these disorders. Maintenance of cellular nucleotides depends on the three aspects of metabolism of purines (and related pyrimidines): de novo synthesis, catabolism and recycling of these metabolites. At present, treatments for the clinically significant defects of the purine pathway are restricted: purine 5'-nucleotidase deficiency with uridine; familial juvenile hyperuricaemic nephropathy (FJHN), adenine phosphoribosyl transferase (APRT) deficiency, hypoxanthine phosphoribosyl transferase (HPRT) deficiency and phosphoribosyl-pyrophosphate synthetase superactivity (PRPS) with allopurinol; adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies have been treated by bone marrow transplantation (BMT), and ADA deficiency with enzyme replacement with polyethylene glycol (PEG)-ADA, or erythrocyte-encapsulated ADA; myeloadenylate deaminase (MADA) and adenylosuccinate lyase (ADSL) deficiencies have had trials of oral ribose; PRPS, HPRT and adenosine kinase (ADK) deficiencies with S-adenosylmethionine; and molybdenum cofactor deficiency of complementation group A (MOCODA) with cyclic pyranopterin monophosphate (cPMP). In this review we describe the known inborn errors of purine metabolism, their phenotypic presentations, established diagnostic methodology and recognised treatment options.

Analysis of multiple transcriptomes of the African oil palm (Elaeis guineensis) to identify reference genes for RT-qPCR

The African oil palm (Elaeis guineensis), which is grown in tropical and subtropical regions, is a highly productive oil-bearing crop. For gene expression-based analyses such as reverse transcription-quantitative real time PCR (RT-qPCR), reference genes are essential to provide a baseline with which to quantify relative gene expression. Normalization using reliable reference genes is critical in correctly interpreting expression data from RT-qPCR. In order to identify suitable reference genes in African oil palm, 17 transcriptomes of different tissues obtained from NCBI were systematically assessed for gene expression variation. In total, 53 putative candidate reference genes with coefficient of variation values <3.0 were identified: 18 in reproductive tissue and 35 in vegetative tissue. Analysis for enriched functions showed that approximately 90% of identified genes were clustered in cell component gene functions, and 12 out of 53 genes were traditional housekeeping genes. We selected and validated 16 reference genes chosen from leaf tissue transcriptomes by using RT-qPCR in sets of cold, drought and high salinity treated samples, and ranked expression stability using statistical algorithms geNorm, Normfinder and Bestkeeper. Genes encoding actin, adenine phosphoribosyltransferase and eukaryotic initiation factor 4A genes were the most stable genes over the cold, drought and high salinity stresses. Identification of stably expressed genes as reference gene candidates from multiple transcriptome datasets was found to be reliable and efficient, and some traditional housekeeping genes were more stably expressed than others. We provide a useful molecular genetic resource for future gene expression studies in African oil palm, facilitating molecular genetics approaches for crop improvement in this species.

Insertion of core CpG island element into human CMV promoter for enhancing recombinant protein expression stability in CHO cells.

The human cytomegalovirus promoter (hCMV) is susceptible to gene silencing in CHO cells, most likely due to epigenetic events, such as DNA methylation and histone modifications. The core CpG island element (IE) from the hamster adenine phosphoribosyltransferase gene has been shown to prevent DNA methylation. A set of modified hCMV promoters was developed by inserting one or two copies of IE in either forward or reverse orientations either upstream of the hCMV enhancer, between the enhancer and core promoter (CP), or downstream of the CP. The modified hCMV with one copy of IE inserted between the enhancer and core promoter in reverse orientation (MR1) was most effective at enhancing expression stability without compromising expression level when compared with the wild-type (WT) hCMV. A third of 18 EGFP expressing clones generated using MR1 retained 70% of their starting expression level after 8 weeks of culture in the absence of selection pressure, while none of 18 WT hCMV generated clones had expression above 50%. MR1 also improved antibody expression stability of methotrexate (MTX) amplified CHO cell lines. Stably transfected pools generated using MR1 maintained 62% of their original monoclonal antibody titer after 8 weeks of culture in the absence of MTX, compared to only 37% for WT hCMV pools. Low levels of CpG methylation within both WT hCMV and MR1 were observed in all the analyzed cell lines and the methylation levels did not correlate to the expression stability, suggesting IE enhances expression stability by other mechanisms other than preventing methylation.

Adenine Phosphoribosyltransferase Deficiency: An Under-Recognized Cause of Urolithiasis and Renal Failure

Early diagnosis of monogenic forms of urolithiasis is important to prevent associated renal injury and other treatable disease manifestations, but is often delayed due to lack of knowledge of these rare disorders. Adenine phosphoribosyltransferase (APRT) deficiency is an under-recognized autosomal recessive disorder causing 2,8 dihydroxyadenine (2,8-DHA) urolithiasis and crystalline nephropathy secondary to intratubular 2,8-DHA crystalline precipitation. Patients often present with kidney stones but may also present with renal failure in the absence of stones or nephrocalcinosis. The disease can be efficiently treated by inhibitors of xanthine dehydrogenease (XDH), which makes early diagnosis and treatment essential to prevent recurrence of urolithiasis and nephropathy. Here, we reviewed 67 patients from 56 families with complete APRT deficiency identified at Necker Universitary Hospital, Paris, France, between 1978 and 2014. The initial clinical presentation was urolithiasis in all symptomatic pediatric patients. In adult patients, recurrent nephrolithiasis was a much more common presentation (73%) than crystalline nephropathy (27%). Unfortunately, APRT deficiency was often misdiagnosed and irreversible loss of renal function occurred in 20% of cases. APRT gene sequencing was performed in 54 patients (81%) in 46 families: 25 pediatric patients in 22 families and 29 adult patients in 26 families. 98 mutated alleles were found out of 108 analyzed (91%). Twenty seven different mutations were identified. A single T insertion at the intron 4 splice donor site (c.400+2dup) leading to a truncated protein, accounted for 36 percent of mutated alleles for pediatric and adult cases. This review summarizes the genetic data of a large cohort of pediatric and adult patients along with the issues for diagnosis and management of APRT deficiency and highlights the underdiagnosis associated with the potential severity of APRT deficiency. Early diagnosis is essential for treatment initiation and prevention of renal complications.

Imaging Characteristics of 2,8-Dihydroxyadenine Stones: Review of a Rare Disorder

Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic condition that often presents with recurrent dihydroxyadenine (DHA) urolithiasis. To our knowledge, no CT imaging of DHA stones has been previously reported in English medical literature. We report a case of an 86-year-old woman with a large DHA stone in her upper left ureter. On CT imaging the stone was low density and had an unusual linear central lucency. We also review the literature for this rare disorder. World J Nephrol Urol. 2014;3(4):154-156 doi: http://dx.doi.org/10.14740/wjnu160w

Adenine phosphoribosyltransferase deficiency: Leave no stone unturned

Adenine phosphoribosyltransferase deficiency: Leave no stone unturned