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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Adenine Phosphoribosyltransferase Deficiency" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2019/09/26" /><meta name="citation_author" content="Vidar Orn Edvardsson" /><meta name="citation_author" content="Amrik Sahota" /><meta name="citation_author" content="Runolfur Palsson" /><meta name="citation_pmid" content="22934314" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK100238/" /><meta name="citation_keywords" content="2,8-Dihydroxyadeninuria" /><meta name="citation_keywords" content="APRT Deficiency" /><meta name="citation_keywords" content="2,8-Dihydroxyadeninuria" /><meta name="citation_keywords" content="APRT Deficiency" /><meta name="citation_keywords" content="Adenine phosphoribosyltransferase" /><meta name="citation_keywords" content="APRT" /><meta name="citation_keywords" content="Adenine Phosphoribosyltransferase Deficiency" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Adenine Phosphoribosyltransferase Deficiency" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Vidar Orn Edvardsson" /><meta name="DC.Contributor" content="Amrik Sahota" /><meta name="DC.Contributor" content="Runolfur Palsson" /><meta name="DC.Date" content="2019/09/26" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK100238/" /><meta name="description" content="Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production and renal excretion of 2,8-dihydroxyadenine (DHA), which leads to kidney stone formation and crystal-induced kidney damage (i.e., DHA crystal nephropathy) causing acute kidney injury episodes and progressive chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected persons symptoms do not occur until adulthood. If adequate treatment is not provided, approximately 20%-25% of affected individuals develop end-stage renal disease (ESRD), usually in adult life." /><meta name="og:title" content="Adenine Phosphoribosyltransferase Deficiency" /><meta name="og:type" content="book" /><meta name="og:description" content="Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production and renal excretion of 2,8-dihydroxyadenine (DHA), which leads to kidney stone formation and crystal-induced kidney damage (i.e., DHA crystal nephropathy) causing acute kidney injury episodes and progressive chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected persons symptoms do not occur until adulthood. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK100238_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK100238_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/adams-oliver/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/ada2-def/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK100238_"><span class="title" itemprop="name">Adenine Phosphoribosyltransferase Deficiency</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: 2,8-Dihydroxyadeninuria; APRT Deficiency</div><p class="contrib-group"><span itemprop="author">Vidar Orn Edvardsson</span>, MD, <span itemprop="author">Amrik Sahota</span>, PhD, and <span itemprop="author">Runolfur Palsson</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK100238_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK100238_ai__"><div class="contrib half_rhythm"><span itemprop="author">Vidar Orn Edvardsson</span>, MD<div class="affiliation small">Division of Pediatric Nephrology
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Children's Medical Center
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Landspítali –The National University Hospital of Iceland
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Reykjavik, Iceland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="si.ilatipsdnal@eradiv" class="oemail">si.ilatipsdnal@eradiv</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Amrik Sahota</span>, PhD<div class="affiliation small">Department of Genetics
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Rutgers University
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Piscataway, New Jersey<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.sregtur.ygoloib@atohas" class="oemail">ude.sregtur.ygoloib@atohas</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Runolfur Palsson</span>, MD<div class="affiliation small">Division of Nephrology
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Landspítali –The National University Hospital of Iceland
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University of Iceland
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Reykjavik, Iceland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="si.ilatipsdnal@ruflonur" class="oemail">si.ilatipsdnal@ruflonur</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">August 30, 2012</span>; Last Update: <span itemprop="dateModified">September 26, 2019</span>.</p><p><em>Estimated reading time: 22 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="aprt-def.Summary" itemprop="description"><h2 id="_aprt-def_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production and renal excretion of 2,8-dihydroxyadenine (DHA), which leads to kidney stone formation and crystal-induced kidney damage (i.e., DHA crystal nephropathy) causing acute kidney injury episodes and progressive chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected persons symptoms do not occur until adulthood. If adequate treatment is not provided, approximately 20%-25% of affected individuals develop end-stage renal disease (ESRD), usually in adult life.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of APRT deficiency is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> by absence of APRT enzyme activity in red cell lysates or identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>APRT</i>. The detection of the characteristic round, brown DHA crystals by urine microscopy is highly suggestive of the disorder.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment with the xanthine oxidoreductase inhibitors (XOR; xanthine dehydrogenase/oxidase) allopurinol or febuxostat can improve kidney function, even in individuals with advanced CKD. The prescribed dose of allopurinol and febuxostat should not routinely be reduced in affected individuals who have impaired kidney function. Ample fluid intake is advised. Surgical management of DHA nephrolithiasis is the same as for other types of kidney stones. ESRD is treated with dialysis and kidney transplantation. Even after kidney transplantation, treatment with an XOR is recommended.</p><p><i>Surveillance:</i> Measurement of eGFR and urinary DHA excretion (or urine microscopy for assessment of DHA crystalluria) every 6-12 months; routine follow up to facilitate adherence to pharmacologic treatment at least annually; periodic renal ultrasound examination should be considered to evaluate for new asymptomatic kidney stones.</p><p><i>Agents/circumstances to avoid:</i> Azathioprine and mercaptopurine should not be given to individuals taking either allopurinol or febuxostat.</p><p><i>Evaluation of relatives at risk:</i> It is recommended that sibs of an affected individual undergo APRT enzyme activity measurement or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (if the pathogenic variants in a family have been identified) to allow early diagnosis and treatment and improve long-term outcome.</p><p><i>Pregnancy management:</i> The safety of allopurinol and febuxostat in human pregnancy has not been systematically studied. Some post-transplantation immunosuppressive therapies can have adverse effects on the developing fetus. Ideally a thorough discussion of the risks and benefits of maternal medication use during pregnancy should take place with an appropriate health care provider prior to conception.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>APRT deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being normal. Carrier testing for at-risk relatives and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk are possible if the pathogenic variants in the family have been identified.</p></div></div><div id="aprt-def.Diagnosis"><h2 id="_aprt-def_Diagnosis_">Diagnosis</h2><div id="aprt-def.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Adenine phosphoribosyltransferase (APRT) deficiency (also known as 2,8-dihydroxyadeninuria) <b>should be suspected</b> in individuals with the following clinical, radiographic, laboratory, and pathology findings [<a class="bk_pop" href="#aprt-def.REF.balasubramaniam.2016.800">Balasubramaniam et al 2016</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>, <a class="bk_pop" href="#aprt-def.REF.garigali.2019.23">Garigali et al 2019</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>].</p><p>
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<b>Clinical manifestations</b>
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</p><ul><li class="half_rhythm"><div>Kidney stone disease and renal colic</div></li><li class="half_rhythm"><div>Chronic kidney disease (CKD)</div></li><li class="half_rhythm"><div>Crystal nephropathy (confirmed by kidney biopsy; see <b>Pathology</b>)</div></li><li class="half_rhythm"><div>Reddish-brown diaper stain in infants and young children</div></li><li class="half_rhythm"><div>Allograft dysfunction following kidney transplantation</div></li></ul><p>
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<b>Radiographic findings</b>
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</p><ul><li class="half_rhythm"><div>Radiolucent kidney stones, detected by ultrasound or computed tomography (CT). Stones are not seen on a plain abdominal x-ray.</div></li><li class="half_rhythm"><div>Ultrasound examination frequently demonstrates increased echogenicity of the kidneys.</div></li></ul><p>
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<b>Laboratory findings</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Urine microscopy.</b> The round and brown DHA crystals can usually be detected by urine microscopy (<a class="figpopup" href="/books/NBK100238/figure/aprt-def.F1/?report=objectonly" target="object" rid-figpopup="figaprtdefF1" rid-ob="figobaprtdefF1">Figure 1A</a>). Small and medium-sized DHA crystals display a central Maltese cross pattern when viewed by polarized light microscopy (<a class="figpopup" href="/books/NBK100238/figure/aprt-def.F1/?report=objectonly" target="object" rid-figpopup="figaprtdefF1" rid-ob="figobaprtdefF1">Figure 1B</a>), while larger crystal aggregates do not as they are impermeable to light.</div><div class="half_rhythm">Note: (1) DHA crystals may be difficult to identify in individuals with advanced CKD, possibly due to reduced DHA clearance by the kidney [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.edvardsson.2013.1923">Edvardsson et al 2013</a>]. (2) High urine pH in individuals with radiolucent stones provides an additional clue to the diagnosis of APRT deficiency because uric acid stones develop in acidic urine [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2013.1923">Edvardsson et al 2013</a>] (see <a href="#aprt-def.Differential_Diagnosis">Differential Diagnosis</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Kidney stone analysis.</b> Analysis of DHA crystals and kidney stone material using infrared or ultraviolet spectrophotometry (at both acidic and alkaline pH) and/or x-ray crystallography differentiates DHA from uric acid and xanthine, which also form radiolucent stones. Although stones in persons with APRT deficiency are predominantly composed of DHA, they may contain trace amounts of other minerals.</div><ul><li class="half_rhythm"><div>Kidney stone analysis using the above techniques is dependent on skilled personnel and, thus, cannot be used to establish a diagnosis of APRT deficiency (see <a href="#aprt-def.Establishing_the_Diagnosis">Establishing the Diagnosis</a>).</div></li><li class="half_rhythm"><div>Stone analysis employing standard chemical and thermogravimetric methods does not distinguish DHA from other purines (e.g., uric acid) and is not recommended.</div></li></ul></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figaprtdefF1" co-legend-rid="figlgndaprtdefF1"><a href="/books/NBK100238/figure/aprt-def.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figaprtdefF1" rid-ob="figobaprtdefF1"><img class="small-thumb" src="/books/NBK100238/bin/aprt-def-Image001.gif" src-large="/books/NBK100238/bin/aprt-def-Image001.jpg" alt="Figure 1. . Urinary 2,8-dihydroxyadenine (DHA) crystals from an individual with adenine phosphoribosyltransferase deficiency." /></a><div class="icnblk_cntnt" id="figlgndaprtdefF1"><h4 id="aprt-def.F1"><a href="/books/NBK100238/figure/aprt-def.F1/?report=objectonly" target="object" rid-ob="figobaprtdefF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Urinary 2,8-dihydroxyadenine (DHA) crystals from an individual with adenine phosphoribosyltransferase deficiency. These crystals have a characteristic appearance and polarization pattern. A. Conventional light microscopy shows the typical brown DHA crystals. <a href="/books/NBK100238/figure/aprt-def.F1/?report=objectonly" target="object" rid-ob="figobaprtdefF1">(more...)</a></p></div></div><p><b>Pathology.</b> Renal histopathologic findings in persons with APRT deficiency and CKD or acute allograft dysfunction are characterized by diffuse tubulointerstitial DHA crystal deposits accompanied by inflammation and fibrosis (see <a class="figpopup" href="/books/NBK100238/figure/aprt-def.F2/?report=objectonly" target="object" rid-figpopup="figaprtdefF2" rid-ob="figobaprtdefF2">Figure 2</a>), which may be observed even in individuals without a history of kidney stones [<a class="bk_pop" href="#aprt-def.REF.nasr.2010.1909">Nasr et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.zaidan.2014.2623">Zaidan et al 2014</a>, <a class="bk_pop" href="#aprt-def.REF.agrawal.2015.a17">Agrawal et al 2015</a>, <a class="bk_pop" href="#aprt-def.REF.lusco.2017.e15">Lusco et al 2017</a>].</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figaprtdefF2" co-legend-rid="figlgndaprtdefF2"><a href="/books/NBK100238/figure/aprt-def.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figaprtdefF2" rid-ob="figobaprtdefF2"><img class="small-thumb" src="/books/NBK100238/bin/aprt-def-Image002.gif" src-large="/books/NBK100238/bin/aprt-def-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndaprtdefF2"><h4 id="aprt-def.F2"><a href="/books/NBK100238/figure/aprt-def.F2/?report=objectonly" target="object" rid-ob="figobaprtdefF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Kidney biopsy findings from an individual with adenine phosphoribosyltransferase deficiency and kidney failure due to 2,8- dihydroxyadenine crystal nephropathy A. 2,8-dihydroxyadenine crystals are seen within tubular lumens (arrows). Significant tubular <a href="/books/NBK100238/figure/aprt-def.F2/?report=objectonly" target="object" rid-ob="figobaprtdefF2">(more...)</a></p></div></div><p>Note: It is important not to confuse the histopathologic manifestations of DHA crystal nephropathy with those of other crystal nephropathies, particularly those caused by oxalate (particularly primary hyperoxaluria) and uric acid deposits [<a class="bk_pop" href="#aprt-def.REF.nasr.2010.1909">Nasr et al 2010</a>].</p></div><div id="aprt-def.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of APRT deficiency <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with absent APRT enzyme activity in red cell lysates or <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>APRT</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK100238/table/aprt-def.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobaprtdefTmoleculargenetictestinguse">Table 1</a>). See <a class="figpopup" href="/books/NBK100238/figure/aprt-def.F3/?report=objectonly" target="object" rid-figpopup="figaprtdefF3" rid-ob="figobaprtdefF3">Figure 3</a> for a diagnostic algorithm [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2013.1923">Edvardsson et al 2013</a>].</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figaprtdefF3" co-legend-rid="figlgndaprtdefF3"><a href="/books/NBK100238/figure/aprt-def.F3/?report=objectonly" target="object" title="Figure 3. " class="img_link icnblk_img figpopup" rid-figpopup="figaprtdefF3" rid-ob="figobaprtdefF3"><img class="small-thumb" src="/books/NBK100238/bin/aprt-def-Image003.gif" src-large="/books/NBK100238/bin/aprt-def-Image003.jpg" alt="Figure 3. " /></a><div class="icnblk_cntnt" id="figlgndaprtdefF3"><h4 id="aprt-def.F3"><a href="/books/NBK100238/figure/aprt-def.F3/?report=objectonly" target="object" rid-ob="figobaprtdefF3">Figure 3. </a></h4><p class="float-caption no_bottom_margin">Algorithm for diagnostic evaluation of adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadeninuria From Edvardsson et al [2013]. Used with permission.</p></div></div><p>Note: Kidney stone analysis suggesting APRT deficiency is not reliable enough to establish the diagnosis.</p><div id="aprt-def.APRT_Enzyme_Activity"><h4>APRT Enzyme Activity</h4><p>APRT activity measured in red cell lysates ranges from 16 to 32 nmol/hr per mg hemoglobin in healthy individuals. In almost all individuals with APRT deficiency, APRT enzyme activity measured in red cell lysates (or other cell extracts) is absent; however, exceptions do occur. For example, two enzyme <a class="def" href="/books/n/gene/glossary/def-item/isoforms/">isoforms</a> resulting from the following <i>APRT</i> pathogenic variants have substantial activity in red cell lysates:</p><ul><li class="half_rhythm"><div><a href="/books/NBK100238/table/aprt-def.T.aprt_deficiency_notable_aprt/?report=objectonly" target="object" rid-ob="figobaprtdefTaprtdeficiencynotableaprt">p.Val150Phe</a> [<a class="bk_pop" href="#aprt-def.REF.deng.2001.260">Deng et al 2001</a>] (present in some individuals of northern European heritage)</div></li><li class="half_rhythm"><div><a href="/books/NBK100238/table/aprt-def.T.aprt_deficiency_notable_aprt/?report=objectonly" target="object" rid-ob="figobaprtdefTaprtdeficiencynotableaprt">p.Met136Thr</a> [<a class="bk_pop" href="#aprt-def.REF.ikeda.2016.34">Ikeda et al 2016</a>] (present in >70% of Japanese, who are <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> for this <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>)</div></li></ul><p>Thus, in individuals with these two pathogenic variants, in vivo assays (e.g., uptake of adenine by intact erythrocytes or leukocytes) are required to verify APRT deficiency.</p><p>Note: (1) If enzyme activity is within normal limits or in the <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> range in an individual who has recently received a red cell transfusion, enzyme activity measurement should be repeated after three months. (2) Heterozygotes for an <i>APRT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be reliably identified by enzyme assay in cell extracts as the enzyme activity range in these individuals overlaps with that of controls.</p></div><div id="aprt-def.Molecular_Genetic_Testing"><h4>Molecular Genetic Testing</h4><p>Approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> and use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>APRT</i> is performed first and followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> if only one or no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>APRT</i> and other genes of interest (see <a href="#aprt-def.Differential_Diagnosis">Differential Diagnosis</a>) may be considered. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><div id="aprt-def.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Adenine Phosphoribosyltransferase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>APRT</i>
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</td><td headers="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3, 4</sup></td><td headers="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~87% <sup>5</sup></td></tr><tr><td headers="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>6</sup></td><td headers="hd_h_aprt-def.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare <sup>7</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="aprt-def.TF.1.1"><p class="no_margin">See <a href="/books/NBK100238/#aprt-def.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="aprt-def.TF.1.2"><p class="no_margin">See <a href="#aprt-def.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="aprt-def.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="aprt-def.TF.1.4"><p class="no_margin">Approximately 50 pathogenic variants have been identified in the <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> of <i>APRT</i> in >400 affected individuals from >25 countries, including at least 200 individuals from Japan (see <a href="#aprt-def.Molecular_Genetics">Molecular Genetics</a>).</p></div></dd><dt>5. </dt><dd><div id="aprt-def.TF.1.5"><p class="no_margin">DNA <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> of the <i>APRT</i> <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> and <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a>/<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> junctions from 31 affected individuals (62 chromosomes) with complete APRT deficiency failed to identify 13% of the mutated alleles [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>]. It remains to be determined whether pathogenic variants occur outside of the sequenced regions or are due to <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> changes.</p></div></dd><dt>6. </dt><dd><div id="aprt-def.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>7. </dt><dd><div id="aprt-def.TF.1.7"><p class="no_margin">Rare deletions of both <i>APRT</i> and <i>GALNS</i>, as well as a complex 254-bp <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> with 8-bp <a class="def" href="/books/n/gene/glossary/def-item/insertion/">insertion</a>, have been described (see <a href="#aprt-def.Molecular_Genetics">Molecular Genetics</a>).</p></div></dd></dl></div></div></div><p>Note that enzyme activity measurements in cell extracts alone may not be sufficient to determine the functional significance of novel variants (see <a href="#aprt-def.APRT_Enzyme_Activity">APRT Enzyme Activity</a>).</p></div></div></div><div id="aprt-def.Clinical_Characteristics"><h2 id="_aprt-def_Clinical_Characteristics_">Clinical Characteristics</h2><div id="aprt-def.Clinical_Description"><h3>Clinical Description</h3><p>More than 400 individuals with adenine phosphoribosyltransferase (APRT) deficiency have been reported in the medical literature [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.boll_e.2012.1521">Bollée et al 2012</a>, <a class="bk_pop" href="#aprt-def.REF.harambat.2012.571">Harambat et al 2012</a>, <a class="bk_pop" href="#aprt-def.REF.balasubramaniam.2014.669">Balasubramaniam et al 2014</a>, <a class="bk_pop" href="#aprt-def.REF.zaidan.2014.2623">Zaidan et al 2014</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>, <a class="bk_pop" href="#aprt-def.REF.huq.2018.bcr2018225742">Huq et al 2018</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019b.144">Runolfsdottir et al 2019b</a>].</p><div id="aprt-def.T.presenting_renal_manifestatio" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Presenting Renal Manifestations in APRT Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.presenting_renal_manifestatio/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.presenting_renal_manifestatio_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Presenting Renal Manifestation</th><th id="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Approximate Frequency</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kidney stone disease <sup>1</sup></td><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60%-90%</td></tr><tr><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chronic kidney disease <sup>2, 3</sup></td><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>50%</td></tr><tr><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Acute kidney injury <sup>4</sup></td><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30% <sup>5</sup></td></tr><tr><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">End-stage renal disease</td><td headers="hd_h_aprt-def.T.presenting_renal_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15%</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="aprt-def.TF.2.1"><p class="no_margin">In both children and adults</p></div></dd><dt>2. </dt><dd><div id="aprt-def.TF.2.2"><p class="no_margin">In adult life</p></div></dd><dt>3. </dt><dd><div id="aprt-def.TF.2.3"><p class="no_margin">Due to DHA crystal nephropathy</p></div></dd><dt>4. </dt><dd><div id="aprt-def.TF.2.4"><p class="no_margin">Due to urinary tract obstruction</p></div></dd><dt>5. </dt><dd><div id="aprt-def.TF.2.5"><p class="no_margin">
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<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al [2016]</a>
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||
</p></div></dd></dl></div></div></div><p><b>Age at presentation.</b> APRT deficiency may present at any age; there is no typical age of clinical onset. However, in at least 50% of affected individuals, symptoms do not occur until adulthood.</p><ul><li class="half_rhythm"><div>The age at diagnosis among individuals in the APRT Deficiency Registry of the Rare Kidney Stone Consortium (RKSC) ranged from six months to 72 years (median age: 37 years) [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>].</div></li><li class="half_rhythm"><div>Approximately 35% of persons with APRT deficiency are diagnosed before age 18 years.</div></li><li class="half_rhythm"><div>In a significant number of asymptomatic individuals, a diagnosis of APRT deficiency has been suggested by the detection of DHA crystals on routine urine microscopy or through the screening of sibs of affected individuals and subsequently confirmed by enzyme activity or genetic testing.</div></li></ul><p>Of note, abdominal ultrasound and CT examinations performed for other reasons may identify kidney stones in individuals with APRT deficiency who may be otherwise asymptomatic [<a class="bk_pop" href="#aprt-def.REF.huq.2018.bcr2018225742">Huq et al 2018</a>].</p><p><b>Kidney stone disease.</b> Between 60% and 90% of affected individuals have already developed kidney stones at diagnosis. In the absence of pharmacotherapy (see <b>Management,</b>
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<a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object" rid-ob="figobaprtdefTtargetedtreatmentforpreven">Table 4</a>), the majority of those untreated symptomatic persons experience stone recurrence [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>], abdominal pain, and/or lower urinary tract symptoms (e.g., straining, hesitancy, dribbling, incomplete bladder emptying).</p><p><b>Chronic kidney disease (CKD)</b> secondary to DHA crystal nephropathy is present in more than 50% of individuals at diagnosis [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>]. As many as 15% of affected individuals have progressed to end-stage renal disease (ESRD) at the time of diagnosis of APRT deficiency [<a class="bk_pop" href="#aprt-def.REF.harambat.2012.571">Harambat et al 2012</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>].</p><ul><li class="half_rhythm"><div>In some of these individuals, the diagnosis was not made until after kidney transplantation had been performed.</div></li><li class="half_rhythm"><div>The relatively frequent occurrence of advanced CKD and even ESRD at the time of diagnosis is concerning and suggests a lack of familiarity with this easily treatable condition [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>].</div></li></ul><p><b>ESRD.</b> Approximately 20%-25% of affected individuals develop ESRD, usually in adult life, if adequate treatment is not provided.</p><ul><li class="half_rhythm"><div>Importantly, individuals with APRT deficiency who are diagnosed and treated early with allopurinol or febuxostat have a much more favorable renal outcome [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>] (see <b>Management</b>, <a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object" rid-ob="figobaprtdefTtargetedtreatmentforpreven">Table 4</a>).</div></li><li class="half_rhythm"><div>Timely diagnosis and institution of pharmacologic therapy appears to reduce stone burden and retard or possibly prevent CKD progression to ESRD, even in severely affected individuals.</div></li></ul><p>APRT deficiency is not known to affect organs other than the kidney; however, the authors and other investigators have encountered occasional individuals with APRT deficiency complaining of eye discomfort [<a class="bk_pop" href="#aprt-def.REF.neetens.1986.93">Neetens et al 1986</a>; Author, personal observation], which merits further study.</p></div><div id="aprt-def.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been established; clinical features are known to vary greatly among individuals with the same pathogenic variants [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>].</p></div><div id="aprt-def.Nomenclature"><h3>Nomenclature</h3><p>Originally, two types of APRT deficiency with identical clinical manifestations were described, based on the level of residual APRT activity in cell extracts (erythrocyte lysates) [<a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>]. However, this distinction is of historical interest only, as APRT enzyme activity in intact cells has been shown to be less than 1% in both types [<a class="bk_pop" href="#aprt-def.REF.kamatani.1985.164">Kamatani et al 1985</a>] (see <a href="#aprt-def.APRT_Enzyme_Activity">APRT Enzyme Activity</a>).</p></div><div id="aprt-def.Prevalence"><h3>Prevalence</h3><p>The estimated <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> frequency in different populations ranges from 0.4% to 1.2% [<a class="bk_pop" href="#aprt-def.REF.hidaka.1987.1409">Hidaka et al 1987</a>, <a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>], suggesting that the prevalence of a <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> state is at least 1:50,000 to 1:100,000.</p><p>If this holds true, at least 70,000-80,000 individuals should be affected worldwide, of whom 40,000 would be expected to be in Asia, 9,000 in Europe, and 8,000 in the Americas, including at least 3,000 affected individuals in the US alone. Most of these individuals are currently unrecognized, and thus not benefitting from medical therapy.</p><p>Evidence suggests that APRT deficiency may be a seriously underrecognized cause of kidney stones and crystal nephropathy, progressing over time to ESRD in a significant proportion of untreated individuals [<a class="bk_pop" href="#aprt-def.REF.zaidan.2014.2623">Zaidan et al 2014</a>].</p></div></div><div id="aprt-def.Genetically_Related_Allelic_Dis"><h2 id="_aprt-def_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> have been associated with pathogenic variants in <i>APRT.</i></p></div><div id="aprt-def.Differential_Diagnosis"><h2 id="_aprt-def_Differential_Diagnosis_">Differential Diagnosis</h2><p>Differential diagnosis of APRT deficiency includes other known causes of radiolucent kidney stones such as uric acid nephrolithiasis (OMIM <a href="https://omim.org/entry/605990" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">605990</a>) and xanthinuria (OMIM <a href="https://www.omim.org/phenotypicSeries/PS278300" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS278300</a>).</p><p>The diagnosis of APRT deficiency should be considered in all individuals with chronic kidney disease or kidney failure, particularly in those with renal histopathologic features of crystal nephropathy, even in the absence of a history of nephrolithiasis. Pathologists and physicians must be aware that kidney biopsy findings in persons with APRT deficiency may have a similar appearance to and be confused with those of <a href="/books/n/gene/ph1/">primary hyperoxaluria type 1</a>, <a href="/books/n/gene/ph2/">type 2</a>, and <a href="/books/n/gene/ph3/">type 3</a> [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>].</p></div><div id="aprt-def.Management"><h2 id="_aprt-def_Management_">Management</h2><div id="aprt-def.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs of an individual diagnosed with adenine phosphoribosyltransferase (APRT) deficiency, the evaluations in <a href="/books/NBK100238/table/aprt-def.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobaprtdefTrecommendedevaluationsfollo">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="aprt-def.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with APRT Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Renal</b>
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</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of serum creatinine (&/or cystatin C) concentration</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Urine screening for DHA crystalluria & albuminuria or proteinuria</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ultrasound or CT exam of kidneys</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess kidney stone burden</td></tr><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider kidney biopsy.</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In persons w/↓ renal function &/or proteinuria</td></tr><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider ophthalmologic consultation.</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In those w/ocular or vision symptoms</td></tr><tr><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Miscellaneous/</b>
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<br />
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<b>Other</b>
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||
</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_aprt-def.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DHA = 2,8-dihydroxyadenine</p></div></dd></dl></div></div></div></div><div id="aprt-def.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="aprt-def.T.targeted_treatment_for_preven" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Targeted Treatment for Prevention/Reduction of Kidney Stones in Individuals with APRT Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.targeted_treatment_for_preven_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Goal</th><th id="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dosage</th><th id="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations</th><th id="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Reduction of renal DHA excretion <sup>1</sup></td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Allopurinol <sup>2, 3, 4</sup></td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5-10 mg/kg/day (max dose: 800 mg/day) either 1x/day or in 2 divided doses</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Allopurinol dose should not routinely be reduced in those w/impaired kidney function.</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Lifelong therapy w/allopurinol or febuxostat needed for all patients, even after kidney transplantation; allopurinol or febuxostat can improve kidney function, even in those w/advanced CKD.</td></tr><tr><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Febuxostat <sup>2</sup></td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80 mg/day <sup>5</sup></td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May be more efficacious than allopurinol <sup>6</sup>. Febuxostat dose should not routinely be reduced in those w/impaired kidney function.</td></tr><tr><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reduction of urine DHA supersaturation & crystallization</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ample fluid intake</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May provide an adjunctive benefit to pharmacologic therapy</td><td headers="hd_h_aprt-def.T.targeted_treatment_for_preven_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CKD = chronic kidney disease; DHA = 2,8-dihydroxyadenine; NA = not applicable</p></div></dd><dt>1. </dt><dd><div id="aprt-def.TF.4.1"><p class="no_margin">There are no data to support dietary purine restriction as a treatment of this condition, particularly when treatment with allopurinol or febuxostat is used and urine DHA excretion is already very low.</p></div></dd><dt>2. </dt><dd><div id="aprt-def.TF.4.2"><p class="no_margin">Both allopurinol and febuxostat are oxidoreductase inhibitors (XOR; xanthine dehydrogenase/oxidase).</p></div></dd><dt>3. </dt><dd><div id="aprt-def.TF.4.3"><p class="no_margin">Generally effective and well tolerated</p></div></dd><dt>4. </dt><dd><div id="aprt-def.TF.4.4"><p class="no_margin">Minimizes urinary DHA excretion and crystalluria, stone formation, crystal deposition in the kidney, and development of kidney failure [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.edvardsson.2018.75">Edvardsson et al 2018</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019a.435">Runolfsdottir et al 2019a</a>]</p></div></dd><dt>5. </dt><dd><div id="aprt-def.TF.4.5"><p class="no_margin">No data are available on appropriate dosing for pediatric age groups.</p></div></dd><dt>6. </dt><dd><div id="aprt-def.TF.4.6"><p class="no_margin">A comparison between allopurinol (400 mg/day) and febuxostat (80 mg/day) on urinary DHA excretion found that febuxostat was significantly more efficacious [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2018.75">Edvardsson et al 2018</a>].</p></div></dd></dl></div></div></div><div id="aprt-def.T.treatment_of_manifestations_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with APRT Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.treatment_of_manifestations_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.treatment_of_manifestations_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration/Other</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DHA kidney</b>
|
||
<br />
|
||
<b>stones <sup>1</sup></b>
|
||
</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard surgical management</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl extracorporeal shock wave lithotripsy</td></tr><tr><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>CKD <sup>2</sup></b>
|
||
</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Aggressive management of hypertension</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider ACE inhibitors or angiotensin-receptor blockers in those w/proteinuria.</td></tr><tr><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Standard reduction of cardiovascular risk factors</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ESRD <sup>3</sup></b>
|
||
</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dialysis</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">It is not known if patients on dialysis benefit from allopurinol &/or febuxostat therapy, unless a kidney transplant is planned.</td></tr><tr><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Kidney transplant</td><td headers="hd_h_aprt-def.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In all patients: treatment w/allopurinol or febuxostat for ≥6 wks prior to transplantation, if possible <sup>4</sup>. Lifelong therapy w/allopurinol or febuxostat post transplantation is required to prevent recurrent DHA crystal nephropathy in transplanted organ.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ACE = angiotensin-converting enzyme; CKD = chronic kidney disease; DHA = 2,8-dihydroxyadenine; ESRD = end-stage renal disease</p></div></dd><dt>1. </dt><dd><div id="aprt-def.TF.5.1"><p class="no_margin">For prevention of new kidney stone formation, see <a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object" rid-ob="figobaprtdefTtargetedtreatmentforpreven">Table 4</a>.</p></div></dd><dt>2. </dt><dd><div id="aprt-def.TF.5.2"><p class="no_margin">Including measures to relieve symptoms, control complications, and slow the progression of the disease (See the KDIGO CKD <a href="https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">guideline</a>.)</p></div></dd><dt>3. </dt><dd><div id="aprt-def.TF.5.3"><p class="no_margin">Management of APRT deficiency in those with ESRD</p></div></dd><dt>4. </dt><dd><div id="aprt-def.TF.5.4"><p class="no_margin">Author, unpublished observation</p></div></dd></dl></div></div></div></div><div id="aprt-def.Prevention_of_Primary_Manifesta"><h3>Prevention of Primary Manifestations</h3><p>Adequate treatment of APRT deficiency with allopurinol or febuxostat prevents kidney stone formation and the development of CKD in most, if not all, individuals with the disorder [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2001.473">Edvardsson et al 2001</a>, <a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.harambat.2012.571">Harambat et al 2012</a>] (see <a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object" rid-ob="figobaprtdefTtargetedtreatmentforpreven">Table 4</a>).</p></div><div id="aprt-def.Surveillance"><h3>Surveillance</h3><p>No consensus surveillance guidelines have been established.</p><div id="aprt-def.T.recommended_surveillance_for" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with APRT Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.recommended_surveillance_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.recommended_surveillance_for_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal</b>
|
||
</td><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of eGFR derived from serum creatinine &/or serum cystatin C</td><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos or as clinically indicated</td></tr><tr><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Urine microscopy for assessment of DHA crystalluria <sup>1, 2, 3</sup> if direct DHA measurements not available <sup>4</sup></td></tr><tr><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Renal ultrasound <sup>5</sup></td><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Periodically</td></tr><tr><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess medication compliance.</td><td headers="hd_h_aprt-def.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">eGFR = estimated glomerular filtration rate</p></div></dd><dt>1. </dt><dd><div id="aprt-def.TF.6.1"><p class="no_margin">Using first morning void urine specimen, if possible</p></div></dd><dt>2. </dt><dd><div id="aprt-def.TF.6.2"><p class="no_margin">In those receiving pharmacotherapy</p></div></dd><dt>3. </dt><dd><div id="aprt-def.TF.6.3"><p class="no_margin">Although not optimal, the absence of DHA crystals on urine microscopy can be considered indicative of adequate treatment. A highly significant correlation between 24-hour urinary DHA excretion and DHA crystalluria has been observed [<a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2019b.144">Runolfsdottir et al 2019b</a>].</p></div></dd><dt>4. </dt><dd><div id="aprt-def.TF.6.4"><p class="no_margin">See <a href="#aprt-def.Therapies_and_Assays_Under_Inve">Therapies and Assays Under Investigation</a> for information about the UPLC-MS/MS assay for therapeutic monitoring [<a class="bk_pop" href="#aprt-def.REF.thorsteinsdottir.2016.170">Thorsteinsdottir et al 2016</a>, <a class="bk_pop" href="#aprt-def.REF.edvardsson.2018.75">Edvardsson et al 2018</a>].</p></div></dd><dt>5. </dt><dd><div id="aprt-def.TF.6.5"><p class="no_margin">To evaluate for new, asymptomatic kidney stones</p></div></dd></dl></div></div></div></div><div id="aprt-def.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Azathioprine and mercaptopurine should be avoided by individuals taking XOR inhibitors (allopurinol or febuxostat). Inhibition of xanthine oxidase may cause increased plasma concentrations of azathioprine or mercaptopurine, leading to toxicity.</p></div><div id="aprt-def.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to evaluate apparently asymptomatic sibs of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures. Approximately 15% of individuals with APRT deficiency may be asymptomatic [<a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>, <a class="bk_pop" href="#aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir et al 2016</a>]; these individuals are usually identified during family screening.</p><p>Evaluations can include the following:</p><ul><li class="half_rhythm"><div>Molecular genetic testing if the pathogenic variants in the family are known. Further investigations, including assessment of renal function and urinalysis, are warranted in individuals with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants.</div></li><li class="half_rhythm"><div>APRT enzyme activity measurements, particularly if the pathogenic variants in the family are not known</div></li></ul><p>See <a href="#aprt-def.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="aprt-def.Pregnancy_Management"><h3>Pregnancy Management</h3><p>The safety of allopurinol and febuxostat in human pregnancy has not been systematically studied.</p><p>Animal studies using high doses of allopurinol have revealed evidence of adverse fetal effects in mice but not in rabbits or rats; it is not clear if these effects are a result of direct fetal toxicity or maternal toxicity. Thus, allopurinol should only be prescribed during pregnancy when the benefit of treatment is believed to outweigh the risk. Treatment with allopurinol during pregnancy should be considered in women with APRT deficiency who have CKD with reduced glomerular filtration rate (GFR) or who have undergone kidney transplantation.</p><p>Animal studies using high doses of febuxostat in rats and rabbits have not supported a teratogenic effect. However, very high doses in pregnant rats have been associated with neonatal loss and low pup birthweight.</p><p>Some post-transplantation immunosuppressive therapies can also have adverse effects on the developing fetus.</p><p>A thorough discussion of the risks and benefits of maternal medication use during pregnancy should ideally take place with an appropriate health care provider prior to conception.</p><p>See <a href="https://www.mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for further information on medication use during pregnancy.</p></div><div id="aprt-def.Therapies_and_Assays_Under_Inve"><h3>Therapies and Assays Under Investigation</h3><p><b>Urinary DHA measurements.</b> The authors' group has recently developed a urinary DHA assay using ultra-high-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) [<a class="bk_pop" href="#aprt-def.REF.thorsteinsdottir.2016.170">Thorsteinsdottir et al 2016</a>], which is expected to facilitate both the clinical diagnosis and monitoring of pharmacotherapy of individuals with APRT deficiency [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2018.75">Edvardsson et al 2018</a>]. Further clinical studies to examine the <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> and specificity of the assay are currently under way.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="aprt-def.Genetic_Counseling"><h2 id="_aprt-def_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="aprt-def.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Adenine phosphoribosyltransferase (APRT) deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="aprt-def.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are obligate heterozygotes (i.e., carriers of one <i>APRT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic. Urine microscopy does not reveal DHA crystals and they are not at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of inheriting two <i>APRT</i> pathogenic variants, a 50% chance of inheriting one <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of inheriting two benign alleles.</div></li><li class="half_rhythm"><div>As many as 15%-20% of individuals who have inherited two <i>APRT</i> pathogenic variants may be asymptomatic despite their abnormal urinary DHA excretion [<a class="bk_pop" href="#aprt-def.REF.edvardsson.2001.473">Edvardsson et al 2001</a>, <a class="bk_pop" href="#aprt-def.REF.boll_e.2010.679">Bollée et al 2010</a>]. Such individuals are usually identified during family screening.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic. Urine microscopy does not reveal DHA crystals and they are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Unless an individual with APRT deficiency has children with an affected individual or a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, his/her offspring will be obligate heterozygotes (carriers) for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>APRT</i>.</p><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of an <i>APRT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="aprt-def.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>APRT</i> pathogenic variants in the family.</p></div><div id="aprt-def.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#aprt-def.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p><b>Testing of at-risk asymptomatic sibs</b> of individuals with APRT deficiency is possible after <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> has identified the specific pathogenic variants in the family. Because an effective treatment is available, this testing is appropriate to consider for at-risk sibs regardless of age. However, such testing should be performed in the context of formal <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a>, and is not useful in predicting age at symptom onset, type and severity of symptoms, or rate of progression in asymptomatic individuals.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> status, and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> – including discussion of potential risks to offspring, the availability of effective, preventive drug treatment (see <a href="/books/NBK100238/table/aprt-def.T.targeted_treatment_for_preven/?report=objectonly" target="object" rid-ob="figobaprtdefTtargetedtreatmentforpreven">Table 4</a> and <a href="#aprt-def.Prevention_of_Primary_Manifesta">Prevention of Primary Manifestations</a>), and reproductive options – to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown).</p></div><div id="aprt-def.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>APRT</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> for APRT deficiency are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="aprt-def.Resources"><h2 id="_aprt-def_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>APRT Deficiency Support Network</b>
|
||
</div><div>
|
||
<a href="http://www.rarekidneystones.org/dha/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.rarekidneystones.org/dha/</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>APRT Deficiency Registry of the Rare Kidney Stone Consortium</b>
|
||
</div><div>Landspitali - The National University Hospital of Iceland </div><div>Iceland</div><div><b>Phone:</b> 00-354-543-1000</div><div><b>Fax:</b> 00-354-543-3021</div><div><b>Email:</b> rarekidneystones@landspitali.is</div><div>
|
||
<a href="http://www.rarekidneystones.org/dha/physicians.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">APRT Deficiency Registry</a>
|
||
</div></li></ul>
|
||
</div><div id="aprt-def.Molecular_Genetics"><h2 id="_aprt-def_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="aprt-def.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Adenine Phosphoribosyltransferase Deficiency: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_aprt-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_aprt-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_aprt-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_aprt-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_aprt-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_aprt-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_aprt-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/353" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>APRT</i>
|
||
</a>
|
||
</td><td headers="hd_b_aprt-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=353" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">16q24<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_b_aprt-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P07741" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Adenine phosphoribosyltransferase</a>
|
||
</td><td headers="hd_b_aprt-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/APRT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">APRT database</a>
|
||
</td><td headers="hd_b_aprt-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=APRT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">APRT</a>
|
||
</td><td headers="hd_b_aprt-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=APRT[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">APRT</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="aprt-def.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="aprt-def.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Adenine Phosphoribosyltransferase Deficiency (<a href="/omim/102600,614723" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/102600" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">102600</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ADENINE PHOSPHORIBOSYLTRANSFERASE; APRT</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/614723" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">614723</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY; APRTD</td></tr></tbody></table></div></div><div id="aprt-def.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>APRT</i> is a five-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> with a <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> of 540 bp. <i>APRT</i> encodes APRT, a cytoplasmic enzyme that catalyzes the Mg<sup>++</sup>-dependent synthesis of 5'-adenosine monophosphate from adenine and 5-phosphoribosyl-1-pyrophosphate (PRPP) [<a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>]. The enzyme is a homodimer [<a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>].</p><p>The crystal structure of recombinant human APRT in complex with adenosine monophosphate (AMP) has been determined [<a class="bk_pop" href="#aprt-def.REF.silva.2004.7663">Silva et al 2004</a>]. The protein, which comprises nine β-strands and six α-helices, forms three domains:</p><ul><li class="half_rhythm"><div>A core that includes the PRPP-binding motif</div></li><li class="half_rhythm"><div>A flexible loop besides the core region which may be involved in the catalytic function</div></li><li class="half_rhythm"><div>A variable region primarily involved in base recognition</div></li></ul><p><b>Mechanism of disease causation.</b> APRT deficiency occurs through a <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> mechanism. APRT activity in red cell lysates from individuals with APRT deficiency is typically less than 1% of control values [<a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>]. The two reported exceptions are noted in <a href="/books/NBK100238/table/aprt-def.T.aprt_deficiency_notable_aprt/?report=objectonly" target="object" rid-ob="figobaprtdefTaprtdeficiencynotableaprt">Table 7</a> [<a class="bk_pop" href="#aprt-def.REF.deng.2001.260">Deng et al 2001</a>].</p><p>More than 50 pathogenic variants have been identified in the <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> of <i>APRT</i> in over 300 affected individuals from more than 25 countries, including at least 200 individuals from Japan.</p><p>Rarely, large deletions of both <i>APRT</i> and <i>GALNS</i>, pathogenic variants in which cause <a href="/books/n/gene/mps4a/">mucopolysaccharidosis type IVA</a>, have been reported [<a class="bk_pop" href="#aprt-def.REF.fukuda.1996.123">Fukuda et al 1996</a>, <a class="bk_pop" href="#aprt-def.REF.wang.1999.78">Wang et al 1999</a>]. Of note, a complex <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of 254 base pairs with <a class="def" href="/books/n/gene/glossary/def-item/insertion/">insertion</a> of eight base pairs has also been reported (see <a href="/books/NBK100238/table/aprt-def.T.aprt_deficiency_notable_aprt/?report=objectonly" target="object" rid-ob="figobaprtdefTaprtdeficiencynotableaprt">Table 7</a>).</p><div id="aprt-def.T.aprt_deficiency_notable_aprt" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>APRT Deficiency: Notable <i>APRT</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100238/table/aprt-def.T.aprt_deficiency_notable_aprt/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aprt-def.T.aprt_deficiency_notable_aprt_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000485.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000485<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000476.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000476<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.294G>A<br />(1450G>A)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Trp98Ter</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">The most common pathogenic variants in affected Japanese persons; p.Met136Thr [<a class="bk_pop" href="#aprt-def.REF.sahota.2001">Sahota et al 2001</a>] has decreased affinity for the co-substrate PRPP.</td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000485.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000485<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.258_261dupCCGA<br />(1415_1418insCCGA)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000485.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000485<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000476.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000476<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.407T>C<br />(2066T>C)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met136Thr</td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.194A>T<br />(1350A>T)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asp65Val</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in affected persons from Iceland, Britain, & Spain</td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.400+2dupT<br />(400+2insT)<br />(IVS4+2insT)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala108GlufsTer3<br />(Arg87PfsTer23)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in European populations</td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.448G>T<br />(2107G>T)</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val150Phe</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Identified <a class="def" href="/books/n/gene/glossary/def-item/compound-heterozygous/">compound heterozygous</a> w/c.400+2dupT in a person of northern European heritage who had considerable residual enzyme activity in cell extracts [<a class="bk_pop" href="#aprt-def.REF.deng.2001.260">Deng et al 2001</a>]</td></tr><tr><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000485.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000485<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">del254 bp, insTTCCCGTA</td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aprt-def.T.aprt_deficiency_notable_aprt_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reported in 2 families: 1 from Austria and 1 from Italy [<a class="bk_pop" href="#aprt-def.REF.menardi.1997.251">Menardi et al 1997</a>, <a class="bk_pop" href="#aprt-def.REF.di_pietro.2007.73">Di Pietro et al 2007</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="aprt-def.TF.7.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl></div></div></div></div></div><div id="aprt-def.References"><h2 id="_aprt-def_References_">References</h2><div id="aprt-def.Consensus_Statements__Published"><h3>Consensus Statements / Published Guidelines</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF1">Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. <span><span class="ref-journal">Kidney Int. </span>2013 Suppl 3:1–150. <a href="https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">online</a></span> Available. Accessed 2-28-22.</div></li></ul></div><div id="aprt-def.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.agrawal.2015.a17">Agrawal V, Gibson PC, Sahota A, Nasr SH. Crystalline nephropathy in an identical twin. <span><span class="ref-journal">Am J Kidney Dis. </span>2015;<span class="ref-vol">65</span>:A17–9.</span> [<a href="/pmc/articles/PMC5926183/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5926183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25919501" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25919501</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.balasubramaniam.2016.800">Balasubramaniam GS, Arenas-Hernandez M, Escuredo E, Fairbanks L, Marinaki T, Mapplebeck S, Sheaff M, Almond MK. Adenine phosphoribosyltransferase deficiency in the United Kingdom: two novel mutations and a cross-sectional survey. <span><span class="ref-journal">Clin Kidney J. </span>2016;<span class="ref-vol">9</span>:800–6.</span> [<a href="/pmc/articles/PMC5162415/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5162415</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27994857" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27994857</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.balasubramaniam.2014.669">Balasubramaniam S, Duley JA, Christodoulou J. Inborn errors of purine metabolism: clinical update and therapies. <span><span class="ref-journal">J Inherit Metab Dis. </span>2014;<span class="ref-vol">37</span>:669–86.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24972650" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24972650</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.boll_e.2010.679">Bollée G, Dollinger C, Boutaud L, Guillemot D, Bensman A, Harambat J, Deteix P, Daudon M, Knebelmann B, Ceballos-Picot I. Phenotype and genotype characterization of adenine phosphoribosyltransferase deficiency. <span><span class="ref-journal">J Am Soc Nephrol. </span>2010;<span class="ref-vol">21</span>:679–88.</span> [<a href="/pmc/articles/PMC2844298/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2844298</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20150536" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20150536</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.boll_e.2012.1521">Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I. Adenine phosphoribosyltransferase deficiency. <span><span class="ref-journal">Clin J Am Soc Nephrol. </span>2012;<span class="ref-vol">7</span>:1521–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22700886" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22700886</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.deng.2001.260">Deng L, Yang M, Fründ S, Wessel T, De Abreu RA, Tischfield JA, Sahota A. 2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. <span><span class="ref-journal">Mol Genet Metab. </span>2001;<span class="ref-vol">72</span>:260–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11243733" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11243733</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.di_pietro.2007.73">Di Pietro V, Perruzza I, Amorini AM, Balducci A, Ceccarelli L, Lazzarino G, Barsotti P, Giardina B, Tavazzi B. Clinical, biochemical and molecular diagnosis of a compound homozygote for the 254 bp deletion-8 bp insertion of the APRT gene suffering from severe renal failure. <span><span class="ref-journal">Clin Biochem. </span>2007;<span class="ref-vol">40</span>:73–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17126311" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17126311</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.edvardsson.2001.473">Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. <span><span class="ref-journal">Am J Kidney Dis. </span>2001;<span class="ref-vol">38</span>:473–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11532677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11532677</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.edvardsson.2013.1923">Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, Palsson R. Hereditary causes of kidney stones and chronic kidney disease. <span><span class="ref-journal">Pediatr Nephrol. </span>2013;<span class="ref-vol">28</span>:1923–42.</span> [<a href="/pmc/articles/PMC4138059/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4138059</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23334384" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23334384</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.edvardsson.2018.75">Edvardsson VO, Runolfsdottir HL, Thorsteinsdottir UA, Sch, Agustsdottir IM, Oddsdottir GS, Eiriksson F, Goldfarb DS, Thorsteinsdottir M, Palsson R. Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency (APRTd): a clinical trial. <span><span class="ref-journal">Eur J Intern Med. </span>2018;<span class="ref-vol">48</span>:75–9.</span> [<a href="/pmc/articles/PMC5817015/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5817015</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29241594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29241594</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.fukuda.1996.123">Fukuda S, Tomatsu S, Masuno M, Ogawa T, Yamagishi A, Rezvi GM, Sukegawa K, Shimozawa N, Suzuki Y, Kondo N, Imaizumi K, Kuroki Y, Okabe T, Orii T. Mucopolysaccharidosis IVA: submicroscopic deletion of 16q24.3 and a novel R386C mutation of N-acetylgalactosamine-6-sulfate sulfatase gene in a classical Morquio disease. <span><span class="ref-journal">Hum Mutat. </span>1996;<span class="ref-vol">7</span>:123–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8829629" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8829629</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.garigali.2019.23">Garigali G, Marra G, Rizzo V, de Liso F, Berrettini A, Daudon M, Fogazzi GB. A virtuous diagnostic and therapeutic roadmap triggered by a motivated and skilful urinary sediment examination. <span><span class="ref-journal">Clin Chim Acta. </span>2019;<span class="ref-vol">492</span>:23–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30707895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30707895</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.harambat.2012.571">Harambat J, Bollée G, Daudon M, Ceballos-Picot I, Bensman A, et al. Adenine phosphoribosyltransferase deficiency in children. <span><span class="ref-journal">Pediatr Nephrol. </span>2012;<span class="ref-vol">27</span>:571–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22212387" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22212387</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.hidaka.1987.1409">Hidaka Y, Palella TD, O'Toole TE, Tarle SA, Kelley WN. Human adenine phosphoribosyltransferase. Identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme. <span><span class="ref-journal">J Clin Invest. </span>1987;<span class="ref-vol">80</span>:1409–15.</span> [<a href="/pmc/articles/PMC442397/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC442397</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/3680503" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3680503</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.huq.2018.bcr2018225742">Huq A, Nand K, Juneja R, Winship I. APRT deficiency: the need for early diagnosis. <span><span class="ref-journal">BMJ Case Rep. </span>2018:bcr-2018-225742. </span> pii. 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Use of LightCycler mutation analysis to detect type II adenine phosphoribosyltransferase deficiency in two patients with 2,8-dihydroxyadeninuria. <span><span class="ref-journal">CEN Case Rep. </span>2016;<span class="ref-vol">5</span>:34–9.</span> [<a href="/pmc/articles/PMC5411657/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5411657</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28509161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28509161</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.kamatani.1985.164">Kamatani N, Takeuchi F, Nishida Y, Yamanaka H, Nishioka K, Tatara K, Fujimori S, Kaneko K, Akaoka I, Tofuku Y. Severe impairment in adenine metabolism with a partial deficiency of adenine phosphoribosyltransferase. <span><span class="ref-journal">Metabolism. </span>1985;<span class="ref-vol">34</span>:164–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3871499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3871499</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.lusco.2017.e15">Lusco MA, Fogo AB, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: 2,8-dihydroxyadeninuria. <span><span class="ref-journal">Am J Kidney Dis. </span>2017;<span class="ref-vol">69</span>:e15–e16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28236886" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28236886</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.menardi.1997.251">Menardi C, Schneider R, Neuschmid-Kaspar F, Klocker H, Hirsch-Kauffmann M, Auer B, Schweiger M. Human APRT deficiency: indication for multiple origins of the most common Caucasian mutation and detection of a novel type of mutation involving intrastrand-templated repair. <span><span class="ref-journal">Hum Mutat. </span>1997;<span class="ref-vol">10</span>:251–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9298830" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9298830</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.nasr.2010.1909">Nasr SH, Sethi S, Cornell LD, Milliner DS, Boelkins M, Broviac J, Fidler ME. Crystalline nephropathy due to 2,8-dihydroxyadeninuria: an under-recognized cause of irreversible renal failure. <span><span class="ref-journal">Nephrol Dial Transplant. </span>2010;<span class="ref-vol">25</span>:1909–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20064951" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20064951</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.neetens.1986.93">Neetens A, Van Acker KJ, Marien N. Corneal dystrophy and total adenine phosphoribosyltransferase (APRT) deficiency. <span><span class="ref-journal">Bull Soc Belge Ophtalmol. </span>1986;<span class="ref-vol">213</span>:93–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3487363" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3487363</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.runolfsdottir.2016.431">Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO. 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Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency. <span><span class="ref-journal">J Chromatogr B Analyt Technol Biomed Life Sci. </span>2016;<span class="ref-vol">1036-1037</span>:170–7.</span> [<a href="/pmc/articles/PMC5445224/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5445224</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27770717" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27770717</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.wang.1999.78">Wang L, Ou X, Sebesta I, Vondrak K, Krijt J, Elleder M, Poupetova H, Ledvinova J, Zeman J, Simmonds HA, Tischfield JA, Sahota A. Combined adenine phosphoribosyltransferase and N-acetylgalactosamine-6-sulfate sulfatase deficiency. <span><span class="ref-journal">Mol Genet Metab. </span>1999;<span class="ref-vol">68</span>:78–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10479485" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10479485</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="aprt-def.REF.zaidan.2014.2623">Zaidan M, Palsson R, Merieau E, Cornec-Le Gall E, Garstka A, Maggiore U, Deteix P, Battista M, Gagné ER, Ceballos-Picot I, Duong Van Huyen JP, Legendre C, Daudon M, Edvardsson VO, Knebelmann B. Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure. <span><span class="ref-journal">Am J Transplant. </span>2014;<span class="ref-vol">14</span>:2623–32.</span> [<a href="/pmc/articles/PMC4560835/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4560835</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25307253" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25307253</span></a>]</div></li></ul></div></div><div id="aprt-def.Chapter_Notes"><h2 id="_aprt-def_Chapter_Notes_">Chapter Notes</h2><div id="aprt-def.Author_Notes"><h3>Author Notes</h3><p><b>Vidar Orn Edvardsson, MD</b><br />Children's Medical Center, Office 21-D<br />Landspítali –The National University Hospital of Iceland<br />Hringbraut, 101 Reykjavik, Iceland<br />Tel: +354-543-1000; Fax: + 354-543-3021<br />Email: vidare@landspitali.is and rarekidneystones@landspitali.is</p><p><b>Amrik Sahota, PhD, Consultant<br />APRT Deficiency Research Program</b><br />Department of Genetics<br />Life Sciences Building<br />Rutgers University<br />145 Bevier Road<br />Piscataway, NJ 08854, USA<br />Tel: 732-445-7185; Fax: 732-445-1147<br />Email: sahota@biology.rutgers.edu</p><p><b>Runolfur Palsson, MD</b><br />Division of Nephrology, Office 14-F<br />Landspítali – The National University Hospital of Iceland<br />Hringbraut, 101 Reykjavik, Iceland<br />Tel: +354-543-1000; Fax: + 354-543-6467<br />Email: runolfur@landspitali.is and rarekidneystones@landspitali.is</p><p>The official website of the Rare Kidney Stone Consortium: <a href="http://rarekidneystones.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rarekidneystones.org</a></p><p>The APRT Deficiency Research Program at Landspítali – The National University Hospital of Iceland, headed by Drs Vidar Orn Edvardsson and Runolfur Palsson, is part of the international Rare Kidney Stone Consortium (RKSC) (<a href="http://rarekidneystones.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rarekidneystones.org</a>) founded in 2009 with support from the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of Rare Diseases Research at the US National Institutes of Health.</p></div><div id="aprt-def.Acknowledgments"><h3>Acknowledgments</h3><p>Authors V Edvardsson and R Palsson gratefully acknowledge the support of the Rare Kidney Stone Consortium (U54DK083908), a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research. The Rare Kidney Stone Consortium is funded through a collaboration between NCATS and National Institute of Diabetes and Digestive and Kidney Diseases. We thank Hrafnhildur Linnet Runolfsdottir, MD, Faculty of Medicine, School of Health Sciences, University of Iceland, and Landspítali – The National University Hospital of Iceland, Reykjavik, Iceland, for generating the images of the urinary DHA crystals, and Sverrir Hardarson, MD, Department of Pathology, Landspítali – The National University Hospital of Iceland, for providing the photomicrographs of the kidney biopsy specimens.</p></div><div id="aprt-def.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>26 September 2019 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>18 June 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 August 2012 (me) Review posted live</div></li><li class="half_rhythm"><div>2 May 2012 (ve) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK100238/?report=reader">PubReader</a></li><li><a href="/books/NBK100238/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK100238" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK100238" style="display:none" title="Cite this Page"><div class="bk_tt">Edvardsson VO, Sahota A, Palsson R. Adenine Phosphoribosyltransferase Deficiency. 2012 Aug 30 [Updated 2019 Sep 26]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. 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