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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="HPRT1 Disorders" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2020/08/06" /><meta name="citation_author" content="Hyder A Jinnah" /><meta name="citation_pmid" content="20301328" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1149/" /><meta name="citation_keywords" content="HGprt Deficiency" /><meta name="citation_keywords" content="HPRT Deficiency" /><meta name="citation_keywords" content="Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency" /><meta name="citation_keywords" content="HGprt Deficiency" /><meta name="citation_keywords" content="HPRT Deficiency" /><meta name="citation_keywords" content="Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency" /><meta name="citation_keywords" content="Lesch-Nyhan Disease (LND)" /><meta name="citation_keywords" content="HPRT1-Related Neurologic Dysfunction (HND)" /><meta name="citation_keywords" content="HPRT1-Related Hyperuricemia (HRH)" /><meta name="citation_keywords" content="Hypoxanthine-guanine phosphoribosyltransferase" /><meta name="citation_keywords" content="HPRT1" /><meta name="citation_keywords" content="HPRT1 Disorders" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="HPRT1 Disorders" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Hyder A Jinnah" /><meta name="DC.Date" content="2020/08/06" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1149/" /><meta name="description" content="HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild." /><meta name="og:title" content="HPRT1 Disorders" /><meta name="og:type" content="book" /><meta name="og:description" content="HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. 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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="#__NBK1149_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1149_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/hoxa1-dis/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/costello/" 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="_NBK1149_"><span class="title" itemprop="name"><i>HPRT1</i> Disorders</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: HGprt Deficiency, HPRT Deficiency, Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency</div><p class="contrib-group"><span itemprop="author">Hyder A Jinnah</span>, MD, PhD.</p><a data-jig="ncbitoggler" href="#__NBK1149_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1149_ai__"><div class="contrib half_rhythm"><span itemprop="author">Hyder A Jinnah</span>, MD, PhD<div class="affiliation small">Professor, Departments of Neurology & Human Genetics
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Emory University School of Medicine
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Atlanta, Georgia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.yrome@hannijh" class="oemail">ude.yrome@hannijh</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 25, 2000</span>; Last Update: <span itemprop="dateModified">August 6, 2020</span>.</p><p><em>Estimated reading time: 25 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="lns.Summary" itemprop="description"><h2 id="_lns_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>HPRT1</i> disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of <i>HPRT1</i> disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; <i>HPRT1</i>-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and <i>HPRT1</i>-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of an <i>HPRT1</i> disorder is established in a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive clinical and laboratory findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>HPRT1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> and/or low HGprt enzyme activity identified on biochemical testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Hyperuricemia is most commonly treated with the xanthine oxidase inhibitor allopurinol to reduce the risk for nephropathy, gouty arthritis, and tophi. Febuxostat may be used in case of allopurinol hypersensitivity. Multidisciplinary specialists may be needed to manage the neurologic manifestations. Depending on needs, specialists in medical genetics, neurology, behavioral management, developmental pediatrics, physical medicine and rehabilitation, physical therapy, occupational therapy, speech-language pathology, dentistry, and nephrology may be required.</p><p><i>Surveillance:</i>
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<i>HPRT1</i> disorders are not clinically progressive; however, surveillance is important for all <i>HPRT1</i> disorders. While overproduction of uric acid does not get worse with time, chronic overproduction of uric acid – especially if not well controlled – may lead to cumulative pathology in the kidneys and/or joints. Similarly, new or worsening neurologic problems are not expected over time; however, some evolution of the neurologic problems occurs in the first few years of life, which reflects development of the nervous system in response to a static insult.</p><p><i>Agents/circumstances to avoid:</i> Probenecid and other drugs that increase the risk for precipitation of uric acid in the urinary system and may cause acute renal failure; certain chemotherapy agents, such as methotrexate, that block synthesis or use of purines; periods of relative dehydration because they increase the risk for renal stones or urate nephropathy.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to clarify the status of males at risk for <i>HPRT1</i> disorders immediately after birth in order to identify as early as possible those who would benefit from prompt initiation of xanthine oxidase inhibitors and <a class="def" href="/books/n/gene/glossary/def-item/anticipation/">anticipation</a> of future needs.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>HPRT1</i> disorders are X linked. The risk to sibs of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> depends on the genetic status of the mother. If the mother of the proband has an <i>HPRT1</i> variant, the chance of transmitting it in each pregnancy is 50%: males who inherit a pathogenic <i>HPRT1</i> variant will be affected. Females who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be heterozygotes and will virtually always be clinically normal. If the proband represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family) and if the proband has a known <i>HPRT1</i> variant that cannot be detected in his mother’s leukocyte DNA, the risk to sibs is low but greater than that of the general population because of the possibility of maternal <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. Once an <i>HPRT1</i> pathogenic variant has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> testing for females and prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="lns.GeneReview_Scope"><h2 id="_lns_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div id="lns.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HPRT1</i> Disorders <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_lns.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lesch-Nyhan disease (LND)</div></li><li class="half_rhythm"><div><i>HPRT1</i>-related neurologic dysfunction (HND)</div></li><li class="half_rhythm"><div><i>HPRT1-</i>related hyperuricemia (HRH)</div></li></ul>
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</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="lns.TF.c.1"><p class="no_margin">For synonyms and outdated names see <a href="#lns.Nomenclature">Nomenclature</a>.</p></div></dd></dl></div></div></div></div><div id="lns.Diagnosis"><h2 id="_lns_Diagnosis_">Diagnosis</h2><div id="lns.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>HPRT1</i> disorders, which are associated with deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), <b>should be suspected</b> in males with the following clinical and supportive laboratory findings.</p><p>
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<b>Clinical findings</b>
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</p><div id="lns.T.hprt1_disorders_clinical_findings" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p><i>HPRT1</i> Disorders: Clinical Findings by Phenotype</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.hprt1_disorders_clinical_findings/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.hprt1_disorders_clinical_findings_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_1" style="text-align:left;vertical-align:middle;">HPRT1<br />Phenotype</th><th id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2" colspan="4" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Findings</th></tr><tr><th headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2" id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Hyperuricemia, nephrolithiasis, or gouty arthritis</th><th headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2" id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NDD w/motor impairment resembling severe cerebral palsy</th><th headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2" id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID</th><th headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2" id="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Self-injurious behavior</th></tr></thead><tbody><tr><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lesch-Nyhan disease</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td></tr><tr><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HPRT1</i>-related neurologic dysfunction</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+ to +++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+ to ++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HPRT1</i>-related hyperuricemia</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_1_2 hd_h_lns.T.hprt1_disorders_clinical_findings_1_1_2_4" 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">ID = intellectual disability; NA = not applicable; NDD = neurodevelopmental delay</p></div></dd></dl></div></div></div><p>
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<b>Supportive (but not diagnostic) laboratory findings</b>
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</p><ul><li class="half_rhythm"><div>Hyperuricemia is often evident. Serum uric acid concentration greater than 8 mg/dL defines hyperuricemia in adults; however, the upper limit of normal, which varies by age, is lower in children.</div></li><li class="half_rhythm"><div>The urate:creatinine ratio, calculated from the concentration of uric acid and creatinine in a spot urine, provides a reliable measure of uric acid overproduction. A urate:creatinine ratio greater than two is characteristic for all <i>HPRT1</i> disorders.</div></li><li class="half_rhythm"><div>Uric acid kidney stones or uric acid crystals present in the urine.</div></li></ul><p>Note: Absence of a known family history does not preclude the diagnosis of an <i>HPRT1</i> disorder.</p></div><div id="lns.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The diagnosis of an <i>HPRT1</i> disorder is established in a male proband with suggestive clinical and laboratory findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>HPRT1</i> identified by <a href="#lns.Molecular_Genetic_Testing">molecular genetic testing</a> (see <a href="/books/NBK1149/table/lns.T.molecular_genetic_testing_used_for/?report=objectonly" target="object" rid-ob="figoblnsTmoleculargenetictestingusedfor">Table 2</a>) and/or low HGprt enzyme activity identified on <a href="#lns.Biochemical_Testing">biochemical testing</a>.</p><p>Note: Identification of a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>HPRT1</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out a diagnosis of this disorder.</p><div id="lns.Molecular_Genetic_Testing"><h4>Molecular Genetic Testing</h4><p>Molecular genetic testing can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing and <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>).</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Individuals with the distinctive findings described in <a href="#lns.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <b>Option 1</b>), whereas those in whom the diagnosis of an <i>HPRT1</i> disorder has not been considered are more likely to be diagnosed using genomic testing (see <b>Option 2</b>).</p><p>
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<b>Option 1</b>
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</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>HPRT1</i> is performed first to detect 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. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected.</div><div class="half_rhythm">If no variant is detected by the sequencing method used, the next step is to perform <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> and whole-gene deletions or duplications.</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> (such as those for developmental delay, dystonia, spasticity, intellectual disability, or seizures) that includes <i>HPRT1</i> and other genes of interest (see <a href="#lns.Differential_Diagnosis">Differential Diagnosis</a>) 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>. 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 this condition<i>.</i> (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><p>
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<b>Option 2</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</div><div class="half_rhythm">If <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> is not diagnostic, <b><a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a></b> (when clinically available) may be considered to detect (multi)<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div id="lns.T.molecular_genetic_testing_used_for" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Molecular Genetic Testing Used for <i>HPRT1</i> Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.molecular_genetic_testing_used_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.molecular_genetic_testing_used_for_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.molecular_genetic_testing_used_for_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_lns.T.molecular_genetic_testing_used_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_lns.T.molecular_genetic_testing_used_for_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_lns.T.molecular_genetic_testing_used_for_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HPRT1</i>
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</td><td headers="hd_h_lns.T.molecular_genetic_testing_used_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lns.T.molecular_genetic_testing_used_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~80% <sup>4</sup></td></tr><tr><td headers="hd_h_lns.T.molecular_genetic_testing_used_for_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>5</sup></td><td headers="hd_h_lns.T.molecular_genetic_testing_used_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~20% <sup>4</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="lns.TF.2.1"><p class="no_margin">See <a href="/books/NBK1149/#lns.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="lns.TF.2.2"><p class="no_margin">See <a href="#lns.Molecular_Genetics">Molecular Genetics</a> for information on 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="lns.TF.2.3"><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="lns.TF.2.4"><p class="no_margin"><a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al [2014]</a>, <a class="bk_pop" href="#lns.REF.madeo.2019.147">Madeo et al [2019]</a></p></div></dd><dt>5. </dt><dd><div id="lns.TF.2.5"><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></dl></div></div></div></div><div id="lns.Biochemical_Testing"><h4>Biochemical Testing</h4><p><b>HGprt enzyme activity.</b> Several enzyme tests are clinically available. These tests can be done on any tissue. Although erythrocyte-based assays are most commonly used because they are technically easiest, assays based on cultured fibroblasts correlate better with phenotypic severity [<a class="bk_pop" href="#lns.REF.fu.2015.55">Fu et al 2015</a>].</p><ul><li class="half_rhythm"><div>Individuals with Lesch-Nyhan disease tend to have residual enzyme levels lower than 2%.</div></li><li class="half_rhythm"><div>Individuals with <i>HPRT1</i>-related neurologic dysfunction tend to have residual enzyme activity from 2% to 8%.</div></li><li class="half_rhythm"><div>Individuals with <i>HPRT1</i>-related hyperuricemia tend to have residual enzyme greater than 10%.</div></li></ul></div></div></div><div id="lns.Clinical_Characteristics"><h2 id="_lns_Clinical_Characteristics_">Clinical Characteristics</h2><div id="lns.Clinical_Description"><h3>Clinical Description</h3><div id="lns.Affected_Males"><h4>Affected Males</h4><p>Pathogenic variants in <i>HPRT1</i> are almost always associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) as well as a range of neurobehavioral phenotypes. Historically, three phenotypes recognized in the spectrum of <i>HPRT1</i> disorders were Lesch-Nyhan disease (LND) at the most severe end, the intermediate <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> <i>HPRT1</i>-related neurologic dysfunction (HND), and <i>HPRT1</i>-related hyperuricemia (HRH) at the mild end (see <a href="/books/NBK1149/table/lns.T.hprt1_disorders_clinical_findings/?report=objectonly" target="object" rid-ob="figoblnsThprt1disordersclinicalfindings">Table 1</a>). In reality, these neurobehavioral phenotypes cluster along a continuum from severe to mild [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>].</p><p><b>Overproduction of uric acid</b> is present from birth. The serum uric acid concentration is usually elevated. This finding is often missed because hyperuricemia can be mild; rarely, serum uric acid concentration can be normal.</p><p>If untreated, overproduction of uric acid leads to precipitation of uric acid crystals in the urinary system. Crystals appear as an orange sandy material in the diapers. Larger stones may appear as "gravel" in diapers. Larger stones may be difficult to pass. Stones may cause hematuria and increase the risk for urinary tract infections. While crystals or gravel in the diaper may be an early feature, their significance is often not appreciated for years.</p><p>Another potential consequence of untreated overproduction of uric acid is gouty arthritis caused by precipitation of uric acid in the joints. Complex precipitates mixed with proteins may form visible swellings known as tophi. Gout is uncommon in children and typically develops long after other manifestations are present.</p><p>If overproduction of uric acid is not treated, renal failure is common. Some individuals develop renal failure even with treatment.</p></div><div id="lns.LeschNyhan_Disease_LND"><h4>Lesch-Nyhan Disease (LND)</h4><p>LND is characterized by uric acid overproduction, motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior.</p><p><b>Motor dysfunction.</b> Boys with LND typically have normal prenatal and perinatal histories. The most common initial findings during the first year of life are hypotonia and delayed motor skills. Children with LND fail to reach normal milestones such as sitting, crawling, and walking [<a class="bk_pop" href="#lns.REF.jinnah.2006.1201">Jinnah et al 2006</a>].</p><p>Within the first few years of life, abnormal movements emerge. The characteristic feature in all individuals is severe action dystonia [<a class="bk_pop" href="#lns.REF.jinnah.2006.1201">Jinnah et al 2006</a>]. Children with LND may also develop opisthotonos, choreoathetosis, and sometimes ballismus. Approximately one third develop corticospinal signs such as spasticity, hyperreflexia, and clonus. The neurologic picture resembles dyskinetic or athetoid cerebral palsy.</p><p>The motor disability is sufficiently severe that children with LND do not walk and are usually confined to a wheelchair. Most need assistance with feeding and hygiene.</p><p><b>Cognitive disturbances.</b> Most individuals with LND are cognitively impaired. The degree of impairment is difficult to assess because the neurobehavioral problems make interpretation of standardized tests difficult [<a class="bk_pop" href="#lns.REF.schretlen.2001.805">Schretlen et al 2001</a>].</p><p>In general, individuals with LND do not have severe intellectual disability. Formal psychological testing typically yields scores in the mild-to-moderate range of dysfunction.</p><p><b>Behavioral abnormalities.</b> Almost all affected individuals develop the hallmark feature of recurrent self-injurious behaviors [<a class="bk_pop" href="#lns.REF.schretlen.2005.673">Schretlen et al 2005</a>]. This problem most often develops between ages two and four years. In some instances, it may begin as early as the first year of life, or it may be delayed until the late teenage years.</p><p>Self injury most often involves biting of the fingers, hands, lips, and cheeks [<a class="bk_pop" href="#lns.REF.robey.2003.167">Robey et al 2003</a>]. It may also involve banging the head or limbs against hard objects. The severity and patterns of this behavior evolve over time, but they generally occur daily.</p><p>In addition to self-injurious behavior, affected individuals often have other difficult behaviors including impulsiveness, aggressiveness, oppositional defiance, recurrent vomiting, spitting at others, and coprolalia.</p><p><b>Other manifestations</b> can include the following:</p><ul><li class="half_rhythm"><div>Testicular atrophy with delayed growth and puberty is very common.</div></li><li class="half_rhythm"><div>Macrocytic anemia unresponsive to vitamin supplements is very common, but does not usually require treatment [<a class="bk_pop" href="#lns.REF.cakmakli.2019.353">Cakmakli et al 2019</a>].</div></li><li class="half_rhythm"><div>Neuroimaging often reveals nonspecific changes of atrophy in the central nervous system with reduced cerebral volume and reduced caudate nucleus volume [<a class="bk_pop" href="#lns.REF.schretlen.2013.1151">Schretlen et al 2013</a>].</div></li><li class="half_rhythm"><div>Approximately one third have seizures [<a class="bk_pop" href="#lns.REF.leemanmarkowski.2018">Leeman-Markowski & Jinnah 2018</a>]. EEG shows nonspecific slowing or disorganization in most others.</div></li><li class="half_rhythm"><div>Approximately one third require gastrostomy because of dysphagia and/or recurrent aspiration [<a class="bk_pop" href="#lns.REF.jinnah.2006.1201">Jinnah et al 2006</a>].</div></li><li class="half_rhythm"><div>Uncommon but particularly troublesome problems may include respiratory irregularities such as recurrent unexplained apnea [<a class="bk_pop" href="#lns.REF.neychev.2006.923">Neychev & Jinnah 2006</a>], recurrent unexplained emesis, or dystonic crisis with severe autonomic changes.</div></li></ul><p><b>Life expectancy.</b> LND is not a progressive neurodegenerative disorder [<a class="bk_pop" href="#lns.REF.g_ttle.2014.95">Göttle et al 2014</a>]. If management of manifestations is effective, individuals with LND may survive into the second to fourth decades of life.</p><p>The most common causes of death include pulmonary failure (from pneumonia or recurrent aspiration from dysphagia), renal failure, or sepsis from different causes. Sudden unexplained death in an otherwise well-tended individual may also occur [<a class="bk_pop" href="#lns.REF.neychev.2006.923">Neychev & Jinnah 2006</a>].</p></div><div id="lns.HPRT1Related_Neurologic_Dysfunction"><h4><i>HPRT1</i>-Related Neurologic Dysfunction (HND)</h4><p>HND is similar to LND, except the neurologic features are often less severe and self-injurious behavior does not occur. The spectrum of the severity of neurologic features in HND is broad. The most severely affected individuals are neurologically indistinguishable from those with LND; the least severely affected individuals may have only minor clumsiness with fine motor activity or relatively minor cognitive deficits [<a class="bk_pop" href="#lns.REF.jinnah.2010.671">Jinnah et al 2010</a>]. Intermediate grades of severity may also occur.</p><p>The severity and spectrum of problems related to uric acid are indistinguishable from LND.</p><p>Macrocytic anemia is common, but many of the other problems such as growth delay, dysphagia, seizures, and sudden death are less common.</p><p>Life span is longer than in LND and may be normal for the least severely affected.</p></div><div id="lns.HPRT1Related_Hyperuricemia_HRH"><h4><i>HPRT1</i>-Related Hyperuricemia (HRH)</h4><p>HRH is similar to HND, except that clinically obvious neurologic deficits do not occur. While mild clumsiness may occur, clinically overt problems are not usually apparent and are only evident on detailed neurologic examination [<a class="bk_pop" href="#lns.REF.jinnah.2010.671">Jinnah et al 2010</a>].</p><p>Mild cognitive deficits, especially problems with attention, are common but are not usually identified without formal neuropsychological testing [<a class="bk_pop" href="#lns.REF.schretlen.2001.805">Schretlen et al 2001</a>].</p><p>The severity and spectrum of problems related to uric acid are indistinguishable from LND and HND.</p><p>Life span is normal.</p></div><div id="lns.Heterozygous_Females"><h4>Heterozygous Females</h4><p>Heterozygous females are virtually always clinically normal without evidence for motor or cognitive deficits. Production of uric acid may be slightly elevated, and some <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> females may develop gout when they are older [<a class="bk_pop" href="#lns.REF.puig.1998.950">Puig et al 1998</a>].</p><p>Rarely the LND <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> has been observed in <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> females as the result of skewed (nonrandom) <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a> of the chromosome bearing the normal <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>. (Of note, discordant phenotypes were observed in monozygotic twin girls [1 normal; 1 with LND] due to skewed X-chromosome inactivation [<a class="bk_pop" href="#lns.REF.de_gregorio.2005.70">De Gregorio et al 2005</a>].)</p><p>Presence of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>HPRT1</i> pathogenic variants has also been reported in females [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>].</p></div></div><div id="lns.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Because the amount of residual HGprt enzyme activity correlates with the severity of the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>, <a class="bk_pop" href="#lns.REF.fu.2015.55">Fu et al 2015</a>], some general <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> are seen.</p><p>LND is associated with complete or near-complete loss of enzyme activity from the following types of <i>HPRT1</i> variants:</p><ul><li class="half_rhythm"><div>Loss-of-function variants such as <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> variants or frameshift variants due to small or large insertions or deletions</div></li><li class="half_rhythm"><div>Missense variants with absent or near-absent enzyme activity. These variants may reduce enzyme activity through different mechanisms including impaired kinetic properties, impaired dimerization of HGprt subunits required for functional activity, and poor protein stability.</div></li><li class="half_rhythm"><div>Most (but not all) <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants that result in major changes in the protein <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a></div></li></ul><p>HND is associated with <i>HPRT1</i> variants that result in small amounts of residual enzyme activity (usually 2%-8% of normal):</p><ul><li class="half_rhythm"><div>Most HND-causing variants are <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants.</div></li><li class="half_rhythm"><div>Occasionally variants affect splice sites, leaving a small proportion of correctly spliced transcripts.</div></li><li class="half_rhythm"><div>Rare variants are duplications, which may rarely revert to normal to varying degrees in different tissues, producing <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> with varying residual HGprt enzyme activity [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>].</div></li></ul><p>HRH is associated with <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> <i>HPRT1</i> variants that retain the highest level of abnormal enzyme activity (usually >8% of normal):</p><ul><li class="half_rhythm"><div>Most individuals with the same <i>HPRT1</i> variant have the same <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, although exceptions exist [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>].</div></li><li class="half_rhythm"><div>Splice site variants have been associated with variable phenotypes, sometimes in the same family, presumably due to differences in <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a> fidelity.</div></li><li class="half_rhythm"><div>Some <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants have been associated with variable phenotypes, sometimes in the same family, presumably due to differences in protein stability [<a class="bk_pop" href="#lns.REF.ceballospicot.2013.268">Ceballos-Picot et al 2013</a>].</div></li></ul></div><div id="lns.Nomenclature"><h3>Nomenclature</h3><p>Although LND may also be referred to as Lesch-Nyhan syndrome, Lesch-Nyhan disease is the more accurate term because the cause of phenotypic elements that constitute the disorder is known.</p><p>HRH may also be referred to as Kelley-Seegmiller syndrome.</p></div><div id="lns.Prevalence"><h3>Prevalence</h3><p>The prevalence of LND is approximately 1:380,000. The prevalence of the milder phenotypes (HND and HRH) is not well studied, but they appear to be less common than LND.</p><p><i>HPRT1</i> disorders occur in all populations that have been studied, and with relatively equal frequency.</p></div></div><div id="lns.Genetically_Related_Allelic_Disorder"><h2 id="_lns_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>HPRT1</i>.</p></div><div id="lns.Differential_Diagnosis"><h2 id="_lns_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Lesch-Nyhan disease (LND).</b> When fully developed with the three clinical elements of uric acid overproduction, neurologic dysfunction, and cognitive and behavioral disturbances, the diagnosis of LND is straightforward. There are no other genetic causes of the full <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. The main diagnostic difficulties arise during early stages when all the features are not yet apparent, and in individuals who have milder phenotypes.</p><p>The index of suspicion is raised when developmental delay is associated with evidence of overproduction of uric acid, such as hyperuricemia, uric acid nephrolithiasis or crystals in the urine, or gouty arthritis.</p><p>LND is first suspected when self-injurious behavior emerges. However, self-injurious behaviors occur in other conditions, including nonspecific intellectual disability, autism spectrum disorder, Tourette syndrome, <a href="/books/n/gene/mcleod/">McLeod neuroacanthocytosis syndrome</a>, <a href="/books/n/gene/rett/">Rett syndrome</a>, <a href="/books/n/gene/cdls/">Cornelia de Lange syndrome</a>, <a href="/books/n/gene/glutaric-a1/">glutaric acidemia type 1</a>, <a href="/books/n/gene/fd/">familial dysautonomia</a>, <a href="/books/n/gene/chac/">chorea-acanthocytosis</a>, sensory neuropathy including hereditary sensory neuropathy type 1 (see <a href="/books/n/gene/hsn1/"><i>SPTLC1</i> Hereditary Sensory Neuropathy</a>), and several psychiatric conditions. Finger and lip biting is so severe and so characteristic of LND that it is referred to as a behavioral <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. In other self-injury syndromes, the behavior tends to be less severe, and the topography of behaviors is different, with head banging and/or nonspecific self biting but not biting of the fingers and lips that results in tissue damage.</p></div><div id="lns.Management"><h2 id="_lns_Management_">Management</h2><div id="lns.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and the needs in an individual diagnosed with an <i>HPRT1</i>-related <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, the evaluations summarized in <a href="/books/NBK1149/table/lns.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figoblnsTrecommendedevaluationsfollowing">Tables 3</a>, <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations">4</a>, and <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations_1/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations1">5</a> are recommended. These tables begin with <i>HPRT1</i>-related hyperuricemia (HRH) because these needs are shared by all phenotypes (<a href="/books/NBK1149/table/lns.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figoblnsTrecommendedevaluationsfollowing">Table 3</a>). <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations">Table 4</a> adds the needs for neurologic assessment in <i>HPRT1</i>-related neurologic dysfunction (HND). Since neurologic involvement varies considerably, the assessment must be tailored to individual needs. <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations_1/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations1">Table 5</a> adds the needs for behavioral assessment in Lesch-Nyhan disease (LND).</p><div id="lns.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>HPRT1</i> Disorders: HRH</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.recommended_evaluations_following_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_lns.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hyperuricemia</b>
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</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serum uric acid</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Establish baseline uric acid & need for allopurinol.</td></tr><tr><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Nephropathy</b>
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</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Renal</b>
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<br />
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<b>function</b>
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</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serum chemistry incl BUN & creatinine</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Establish any renal dysfunction.</td></tr><tr><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Urolithiasis</b>
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</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal US for renal calculi</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Establish existence of:
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<ul><li class="half_rhythm"><div>Any renal stones. Note: Uric acid stones are radiolucent & may not appear on std x-rays.</div></li><li class="half_rhythm"><div>Any additional renal pathology (e.g., nephrocalcinosis, dystrophy).</div></li></ul>
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</td></tr><tr><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gout</b>
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</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of joints</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Establish existence of:
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<ul><li class="half_rhythm"><div>Gouty arthritis;</div></li><li class="half_rhythm"><div>Any tophaceous deposits.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Macrocytic anemia</b>
|
||
</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete blood count</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically unresponsive to vitamins & only rarely requires treatment</td></tr><tr><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_lns.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Provide patients & families w/:
|
||
<ul><li class="half_rhythm"><div>Info on nature, MOI, & implications of HRH to help make informed medical & personal decisions;</div></li><li class="half_rhythm"><div>Risk assessment & testing options to clarify genetic status of family members.</div></li></ul>
|
||
</td><td headers="hd_h_lns.T.recommended_evaluations_following_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">BUN = blood urea nitrogen; HRH = <i>HPRT1</i>-related hyperuricemia; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; US = ultrasound</p></div></dd></dl></div></div></div><div id="lns.T.additional_recommended_evaluations" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Additional Recommended Evaluations Following Initial Diagnosis in Individuals with <i>HPRT1</i> Disorders: HND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_recommended_evaluations_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.additional_recommended_evaluations_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_lns.T.additional_recommended_evaluations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Motor</b>
|
||
<br />
|
||
<b>abnormalities</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neurologic eval</div></li><li class="half_rhythm"><div>Developmental eval</div></li><li class="half_rhythm"><div>PT/rehab eval</div></li><li class="half_rhythm"><div>PT/OT eval</div></li></ul>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
|
||
<ul><li class="half_rhythm"><div>Motor disorder;</div></li><li class="half_rhythm"><div>Contractures (& if present, address);</div></li><li class="half_rhythm"><div>Dysarthria;</div></li><li class="half_rhythm"><div>History of seizures;</div></li><li class="half_rhythm"><div>ADL.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Intellectual/</b>
|
||
<br />
|
||
<b>behavioral</b>
|
||
<br />
|
||
<b>problems</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurocognitive & behavioral<br />assessments</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
|
||
<ul><li class="half_rhythm"><div>Cognitive abilities & need for intervention;</div></li><li class="half_rhythm"><div>Any behavioral problems.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Communication</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech-language pathology eval</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess dysarthria & need for intervention.</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding/Nutrition</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition /<br />feeding team eval</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess nutritional status & aspiration risk.</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support/</b>
|
||
<br />
|
||
<b>resources</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Social worker interventions;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; HND = <i>HPRT1</i>-related neurologic dysfunction; OT = occupational therapist; PT = physical therapist</p></div></dd></dl></div></div></div><div id="lns.T.additional_recommended_evaluations_1" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Additional Recommended Evaluations Following Initial Diagnosis in Individuals with <i>HPRT1</i> Disorders: LND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_recommended_evaluations_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.additional_recommended_evaluations_1_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_lns.T.additional_recommended_evaluations_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Self-injurious</b>
|
||
<br />
|
||
<b>behavior</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">History & exam for evidence of self injury</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Poorly controlled self injury leads to multiple scars.</div></li><li class="half_rhythm"><div>Injuries may become infected or life threatening.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Behavioral</b>
|
||
<br />
|
||
<b>assessment</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">History & exam for other difficult behaviors</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assess for oppositional defiant & other difficult behaviors.</div></li><li class="half_rhythm"><div>Provide counseling to therapists & teachers re mgmt of difficult behaviors.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Teeth</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental eval</td><td headers="hd_h_lns.T.additional_recommended_evaluations_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assess for occult biting of oral mucosa & establish plan for tooth extraction when needed.</div></li><li class="half_rhythm"><div>>50% of all persons may need dental extraction because of self biting.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">LND = Lesch-Nyhan disease</p></div></dd></dl></div></div></div></div><div id="lns.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Following initial evaluations (<a href="/books/NBK1149/table/lns.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figoblnsTrecommendedevaluationsfollowing">Tables 3</a>, <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations">4</a>, and <a href="/books/NBK1149/table/lns.T.additional_recommended_evaluations_1/?report=objectonly" target="object" rid-ob="figoblnsTadditionalrecommendedevaluations1">5</a>), treatments for specific problems may be needed. Treatment recommendations are summarized in <a href="/books/NBK1149/table/lns.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figoblnsTtreatmentofmanifestationsinind">Tables 6</a>, <a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu/?report=objectonly" target="object" rid-ob="figoblnsTadditionaltreatmentsforindividu">7</a>, and <a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu_1/?report=objectonly" target="object" rid-ob="figoblnsTadditionaltreatmentsforindividu1">8</a>. They begin with HRH because these needs are shared by all phenotypes (<a href="/books/NBK1149/table/lns.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figoblnsTtreatmentofmanifestationsinind">Table 6</a>). <a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu/?report=objectonly" target="object" rid-ob="figoblnsTadditionaltreatmentsforindividu">Table 7</a> adds the needs for neurologic interventions in HND. Since neurologic involvement varies considerably, needs vary. <a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu_1/?report=objectonly" target="object" rid-ob="figoblnsTadditionaltreatmentsforindividu1">Table 8</a> adds the needs for behavioral interventions in LND [<a class="bk_pop" href="#lns.REF.olson.2000.202">Olson & Houlihan 2000</a>].</p><p>A multidisciplinary team may be needed. Depending on needs, this team may require specialists in medical genetics, neurology, behavioral management, developmental pediatrics, physical medicine and rehabilitation, physical therapy, occupational therapy, speech-language pathology, dentistry, and nephrology.</p><div id="lns.T.treatment_of_manifestations_in_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>HPRT1</i> Disorders: HRH</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.treatment_of_manifestations_in_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.treatment_of_manifestations_in_ind_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_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hyperuricemia</b>
|
||
</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Xanthine oxidase inhibitor</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Allopurinol most commonly used; febuxostat in case of allopurinol hypersensitivity</div></li><li class="half_rhythm"><div>Treatment required to ↓ risk for nephropathy, gouty arthritis, & tophi</div></li><li class="half_rhythm"><div>Titrate to maintain uric acid levels w/in normal limits.</div></li><li class="half_rhythm"><div>Avoid suppressing uric acid below normal limits because this ↑ risk of xanthine stones.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal</b>
|
||
<br />
|
||
<b>complications</b>
|
||
</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Xanthine oxidase inhibitor</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Treatment ↓ risk of renal complications.</div></li><li class="half_rhythm"><div>Avoid dehydration, which concentrates purine metabolites in urinary system.</div></li><li class="half_rhythm"><div>Renal insufficiency or failure may occur despite medical therapy.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Lithotripsy or surgery</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal stones that form despite treatment may require lithotripsy or surgery.</td></tr><tr><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gouty arthritis</b>
|
||
</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Xanthine oxidase inhibitor</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>When gouty arthritis occurs even w/treatment, consider compliance or insufficient hydration.</div></li></ul>
|
||
Tophaceous deposits:
|
||
<ul><li class="half_rhythm"><div>May be painful when they erode overlying skin or underlying tissues;</div></li><li class="half_rhythm"><div>May become infected.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Macrocytic</b>
|
||
<br />
|
||
<b>anemia</b>
|
||
</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_lns.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Folate & B<sub>12</sub> supplements do not usually work.</div></li><li class="half_rhythm"><div>Treatment often is not needed because problem does not produce disability.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">HRH = <i>HPRT1</i>-related hyperuricemia</p></div></dd></dl></div></div></div><div id="lns.T.additional_treatments_for_individu" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Additional Treatments for Individuals with <i>HPRT1</i> Disorders: HND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_treatments_for_individu_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_treatments_for_individu_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_lns.T.additional_treatments_for_individu_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_lns.T.additional_treatments_for_individu_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Motor</b>
|
||
<br />
|
||
<b>impairments</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pharmacologic</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>No medication reliably controls dystonia in HND.</div></li><li class="half_rhythm"><div>Antispasticity agents may be useful for spasticity.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Orthopedic</b>
|
||
<br />
|
||
<b>problems</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT/OT</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Helpful to limit contractures</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Surgical intervention</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedic interventions may be required to address contractures, dislocations, & related problems.</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Intellectual</b>
|
||
<br />
|
||
<b>disability</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#lns.Developmental_Delay__Intellectual_Di">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Cognitive problems may not be apparent w/o neuropsychological testing.</div></li><li class="half_rhythm"><div>Problems w/attention are common & create learning disability.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">HND = <i>HPRT1</i>-related neurologic dysfunction; OT = occupational therapy; PT = physical therapy</p></div></dd></dl></div></div></div><div id="lns.T.additional_treatments_for_individu_1" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p>Additional Treatments for Individuals with <i>HPRT1</i> Disorders: LND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_treatments_for_individu_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_treatments_for_individu_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_treatments_for_individu_1_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_lns.T.additional_treatments_for_individu_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Self-injurious</b>
|
||
<br />
|
||
<b>behavior</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical protective devices (restraints)</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Required by virtually all persons at some point; often required daily</div></li><li class="half_rhythm"><div>LND is exempt from laws that prevent use of restraints for extended periods.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Behavior therapy</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Negative reinforcement methods (punishment) worsen behavior & should not be used.</div></li><li class="half_rhythm"><div>Extinction methods work best, & require special expertise to implement.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Pharmacologic interventions</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>No medications reliably control self injury in LND.</div></li><li class="half_rhythm"><div>Benzodiazepines often used to ↓ anxiety</div></li><li class="half_rhythm"><div>Neuroleptics may worsen the dystonia.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dental interventions</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Tooth & mouth guards rarely reliable</div></li><li class="half_rhythm"><div>Dental extraction required in the majority</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other difficult</b>
|
||
<br />
|
||
<b>behaviors</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavior therapy</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Extinction methods sometimes required to suppress other negative behaviors incl hitting, spitting, or foul language</td></tr><tr><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/</b>
|
||
<br />
|
||
<b>Community</b>
|
||
</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Social worker intervention</td><td headers="hd_h_lns.T.additional_treatments_for_individu_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many families benefit from online chat services where families share experiences.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">LND = Lesch-Nyhan disease</p></div></dd></dl></div></div></div><div id="lns.Developmental_Delay__Intellectual_Di"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services and special educators. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life.</p></div></div><div id="lns.Surveillance"><h3>Surveillance</h3><p><i>HPRT1</i> disorders are not clinically progressive. For example, overproduction of uric acid does not get worse with time. However, chronic overproduction of uric acid over years may lead to cumulative pathology in the kidneys and/or joints, especially if hyperuricemia is not well controlled. Therefore, some surveillance is important for all <i>HPRT1</i> disorders (<a href="/books/NBK1149/table/lns.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" rid-ob="figoblnsTrecommendedsurveillanceforindiv">Table 9</a>). Sudden worsening of renal function should lead to suspicion for new stones or a secondary process.</p><p>Similarly, new or worsening neurologic problems are not expected over time [<a class="bk_pop" href="#lns.REF.jinnah.2006.1201">Jinnah et al 2006</a>, <a class="bk_pop" href="#lns.REF.jinnah.2010.671">Jinnah et al 2010</a>]. Some evolution of the neurologic problems occurs in the first few years of life, which reflects development of the nervous system in response to a static insult and is not a neurodegenerative process. Some evolution of disability may occur with aging, analogous to cerebral palsy. Sudden worsening of neurologic status therefore should be investigated for secondary causes.</p><p>The behavioral <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> may wax and wane in severity over the years. Sudden worsening occurs with stress, for example relating to the pain of a kidney stone or change in social environment. In very young children with HND, self-injurious behavior may emerge, leading to reclassification of the diagnosis to LND. This behavior typically emerges between age two and four years but may be delayed until the teenage years.</p><div id="lns.T.recommended_surveillance_for_indiv" class="table"><h3><span class="label">Table 9. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>HPRT1</i> Disorders: HRH</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.recommended_surveillance_for_indiv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.recommended_surveillance_for_indiv_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.recommended_surveillance_for_indiv_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_lns.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hyperuricemia</b>
|
||
</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serum uric acid</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor 3-6x/yr during allopurinol titration.</div></li><li class="half_rhythm"><div>Annual assessments are sufficient after stable dose is achieved.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal</b>
|
||
<br />
|
||
<b>complications</b>
|
||
</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serum chemistry incl BUN & creatinine</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor annually to assess for renal insufficiency.</td></tr><tr><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Renal US</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Check for:
|
||
<ul><li class="half_rhythm"><div>Urinary system stones if clinically suspected;</div></li><li class="half_rhythm"><div>Evidence of worsening renal function.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gouty arthritis</b>
|
||
</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical exam</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Check at least annually; more often if clinically indicated due to pain or joint swelling.</td></tr><tr><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Plain x-rays</td><td headers="hd_h_lns.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for any joint damage.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">BUN = blood urea nitrogen; HRH = <i>HPRT1</i>-related hyperuricemia; US = ultrasound</p></div></dd></dl></div></div></div><div id="lns.T.additional_recommended_surveillanc" class="table"><h3><span class="label">Table 10. </span></h3><div class="caption"><p>Additional Recommended Surveillance for Individuals with <i>HPRT1</i> Disorders: HND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_recommended_surveillanc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_recommended_surveillanc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.additional_recommended_surveillanc_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_lns.T.additional_recommended_surveillanc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic or developmental assessment for new or worsening problems (e.g., contractures, dysarthria/dysphagia, seizures)</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At least annually</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD/ID</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>New onset of self-injurious or</b>
|
||
<br />
|
||
<b>other deleterious behaviors</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">History & physical exam</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually through teen yrs</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of caregiver needs (e.g., respite care, home nursing, coordination of multiple subspecialty appointments, equipment, medications, & supplies)</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_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">DD = developmental delay; HND = <i>HPRT1</i>-related neurologic dysfunction; ID = intellectual disability</p></div></dd></dl></div></div></div><div id="lns.T.additional_recommended_surveillanc_1" class="table"><h3><span class="label">Table 11. </span></h3><div class="caption"><p>Additional Recommended Surveillance for Individuals with <i>HPRT1</i> Disorders: LND</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.additional_recommended_surveillanc_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.additional_recommended_surveillanc_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_lns.T.additional_recommended_surveillanc_1_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_lns.T.additional_recommended_surveillanc_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Behavioral</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">History & physical exam for evidence of uncontrolled self injury</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">At least annually</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Self biting</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental exam for evidence of occult biting (e.g., of buccal mucosa, tongue)</td></tr><tr><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/</b>
|
||
<br />
|
||
<b>Community</b>
|
||
</td><td headers="hd_h_lns.T.additional_recommended_surveillanc_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of caregiver needs (e.g., respite care, home nursing, coordination of multiple subspecialty appointments, equipment, medications, & supplies)</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">LND = Lesch-Nyhan disease</p></div></dd></dl></div></div></div></div><div id="lns.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid the following:</p><ul><li class="half_rhythm"><div>Probenecid and other drugs that reduce serum uric acid concentration by increasing renal excretion of uric acid; these drugs increase the risk of precipitation of uric acid in the urinary system and may cause acute renal failure.</div></li><li class="half_rhythm"><div>Certain chemotherapy agents, such as methotrexate, that block synthesis or use of purines. Individuals with all <i>HPRT1</i> disorders are especially sensitive to these agents, since all tissue purines derive from purine synthesis when HGprt-mediated purine salvage is deficient.</div></li><li class="half_rhythm"><div>Periods of relative dehydration because they concentrate purine metabolites in the urinary system and increase the risk for renal stones or urate nephropathy</div></li></ul></div><div id="lns.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the status of males at risk for <i>HPRT1</i> disorders immediately after birth in order to identify as early as possible those who would benefit from prompt initiation of xanthine oxidase inhibitors and preparation for future needs.</p><p>See <a href="#lns.Related_Genetic_Counseling_Issues">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="lns.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Numerous small-scale studies have reported benefits from a wide array of therapies including various types of mouth guards and dental appliances, deep brain stimulation, bone marrow transplantation, gabapentin, carbamazepine, S-adenosylmethionine, risperidone, and others. In all instances, follow-up experiences have not confirmed a significant long-term benefit. Because of their follow-on nature and frequent negative outcome, these attempts to confirm benefits often are not published. However, many families post their experience online using social media and, by searching these posts, the clinician can get a good feel for the likelihood that an experimental therapy will have a positive (or negative) impact on the affected individual and their family [<a class="bk_pop" href="#lns.REF.cotton.2018.25">Cotton et al 2018</a>].</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="lns.Genetic_Counseling"><h2 id="_lns_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="lns.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>HPRT1</i> disorders – Lesch-Nyhan disease (LND), <i>HPRT1-</i>related neurologic dysfunction (HND), and <i>HPRT1-</i>related hyperuricemia (HRH) – are X linked. Males who are <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for an <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> are affected. Heterozygous females are virtually always clinically unaffected.</p></div><div id="lns.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disorder nor will he be <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for the <i>HPRT1</i> variant; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is likely to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a>. If a woman has more than one affected child and no other affected relatives and if the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a known <i>HPRT1</i> variant that cannot be detected in her leukocyte DNA, she most likely has <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li><li class="half_rhythm"><div>If a male is the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case), the mother may be a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> or the affected male may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>HPRT1</i> variant, in which case the mother is not a heterozygote. If a woman is the first in her family with an affected son, Haldane's rule predicts a two thirds chance that she is a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> and a one third chance that the son has a <i>de novo</i> <a class="def" href="/books/n/gene/glossary/def-item/germline-variant/">germline variant</a>.</div></li></ul><p><b>Sibs of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs of a male proband depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>HPRT1</i> variant, the chance of transmitting it in each pregnancy is 50%:</div><ul><li class="half_rhythm"><div>Males who inherit a pathogenic <i>HPRT1</i> variant will be affected;</div></li><li class="half_rhythm"><div>Females who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be heterozygotes and will virtually always be clinically normal. In rare instances, a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> female may become symptomatic because of skewed (nonrandom) <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a> of the normal <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>] (see Clinical Description, <a href="#lns.Heterozygous_Females">Heterozygous Females</a>).</div></li></ul></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family) and if the proband has a known <i>HPRT1</i> variant that cannot be detected in his mother’s leukocyte DNA, the risk to sibs is low but greater than that of the general population because of the possibility of maternal <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a> [<a class="bk_pop" href="#lns.REF.willers.2004.737">Willers 2004</a>].</div></li></ul><p>
|
||
<b>Offspring of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Males with LND or HND do not reproduce.</div></li><li class="half_rhythm"><div>Males with HRH transmit the <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> to:</div><ul><li class="half_rhythm"><div>All of their daughters, who will be heterozygotes and will virtually always be clinically normal (see Clinical Description, <a href="#lns.Heterozygous_Females">Heterozygous Females</a>);</div></li><li class="half_rhythm"><div>None of their sons.</div></li></ul></li></ul><p><b>Other family members of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The proband's maternal aunts may be at risk of being heterozygotes, and the aunt's offspring, depending on their sex, may be at risk of being heterozygotes (and virtually always clinically normal) or <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> and affected.</p><p>Molecular genetic testing may be able to identify the family member in whom a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> arose, information that could help determine genetic risk status of the extended family.</p></div><div id="lns.Carrier_Detection"><h3>Carrier Detection</h3><p><b>Molecular genetic testing</b> of at-risk female relatives to determine their genetic status is most informative if the <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</p><p>Note: (1) Females who are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> will virtually always be clinically normal but may have increased uric acid excretion and some may develop hyperuricemia in later years. (2) Identification of female heterozygotes requires either (a) prior identification of the <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the family or, (b) if an affected male is not available for testing, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> first by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, and if no pathogenic variant is identified, by <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>.</p><p><b>Biochemical testing.</b> In females, measurement of HGprt enzyme activity for <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> detection is technically demanding and not widely used.</p></div><div id="lns.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#lns.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>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of genetic 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 and reproductive options) to young adults who are affected, are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a>, or are at risk of being heterozygous.</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="lns.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once an <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has 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 the variant are possible.</p><p><b>Biochemical testing.</b> Assay of HGprt enzyme activity in cultured amniocytes or chorionic villus cells is the preferred method for <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> if the <i>HPRT1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has not been identified in the family [<a class="bk_pop" href="#lns.REF.nyhan.2003.807">Nyhan et al 2003</a>].</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="lns.Resources"><h2 id="_lns_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>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/lesch-nyhan-syndrome/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lesch-Nyhan syndrome</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
|
||
</div><div>PO Box 5801</div><div>Bethesda MD 20824</div><div><b>Phone:</b> 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)</div><div>
|
||
<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Lesch-Nyhan-Syndrome-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lesch-Nyhan Syndrome Information Page</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>NCBI Genes and Disease</b>
|
||
</div><div>
|
||
<a href="/books/NBK22194/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lesch-Nyhan syndrome</a>
|
||
</div></li></ul>
|
||
</div><div id="lns.Molecular_Genetics"><h2 id="_lns_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="lns.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>HPRT1 Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_lns.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_lns.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_lns.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_lns.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_lns.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_lns.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_lns.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/3251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>HPRT1</i>
|
||
</a>
|
||
</td><td headers="hd_b_lns.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=3251" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xq26<wbr style="display:inline-block"></wbr>.2-q26.3</a>
|
||
</td><td headers="hd_b_lns.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P00492" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hypoxanthine-guanine phosphoribosyltransferase</a>
|
||
</td><td headers="hd_b_lns.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/HPRT1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HPRT1 database</a>
|
||
<br />
|
||
<a href="http://www.lesch-nyhan.org/en/research/mutations-database" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lesch-Nyhan<wbr style="display:inline-block"></wbr>.org</a>
|
||
</td><td headers="hd_b_lns.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=HPRT1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HPRT1</a>
|
||
</td><td headers="hd_b_lns.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=HPRT1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HPRT1</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="lns.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="lns.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for HPRT1 Disorders (<a href="/omim/300322,300323,308000" 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/NBK1149/table/lns.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/300322" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300322</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LESCH-NYHAN SYNDROME; LNS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/300323" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300323</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HYPERURICEMIA, HPRT-RELATED; HRH</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/308000" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">308000</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1; HPRT1</td></tr></tbody></table></div></div><div id="lns.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>HPRT1</i> encodes the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), which catalyzes the conversion of hypoxanthine to inosine monophosphate (inosinic acid, IMP) and guanine to guanine monophosphate (guanylic acid, GMP) in the presence of phosphoribosylpyrophosphate. Thus, it recycles purines from DNA and RNA that are otherwise degraded.</p><p><b>Mechanism of disease causation.</b> The proximate etiology is loss of function, or at least reduced function of the HGprt enzyme activity [<a class="bk_pop" href="#lns.REF.fu.2015.55">Fu et al 2015</a>].</p><p>The loss of HGprt-mediated purine recycling leads to secondary changes in purine synthesis, resulting in overproduction of uric acid as a purine waste product. Uric acid is not very soluble in body fluids, so its accumulation results in precipitation in the urinary system (nephrolithiasis) and joints (gouty arthritis).</p><p>The mechanisms responsible for the neurobehavioral <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> are not entirely understood, but are thought to relate to dysfunction of basal ganglia circuits [<a class="bk_pop" href="#lns.REF.visser.2000.449">Visser et al 2000</a>].</p><p><b>Notable <i>HPRT1</i> variants.</b> The majority of <i>HPRT1</i> variants are <a class="def" href="/books/n/gene/glossary/def-item/private/">private</a>, and reported for individual families. However, some variants have arisen multiple times, apparently independently, in unrelated families [<a class="bk_pop" href="#lns.REF.sampat.2011.71">Sampat et al 2011</a>, <a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>]. There are a few recognized hot spots for specific pathogenic variants (see <a href="/books/NBK1149/table/lns.T.notable_hprt1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figoblnsTnotablehprt1pathogenicvariants">Table 12</a>).</p><p>Founder variants occurring in extended families are uncommon because males with LND do not reproduce. Males with HND rarely reproduce, but those with HRH may have families. Therefore, several families with multiple affected members have been reported [<a class="bk_pop" href="#lns.REF.fu.2014.1282">Fu et al 2014</a>].</p><p>For comprehensive information on <i>HPRT1</i> variants, see the database curated by the Lesch-Nyhan Disease International Study Group at <a href="http://www.lesch-nyhan.org/en/research/mutations-database" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.lesch-nyhan.org</a>.</p><div id="lns.T.notable_hprt1_pathogenic_variants" class="table"><h3><span class="label">Table 12. </span></h3><div class="caption"><p>Notable <i>HPRT1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1149/table/lns.T.notable_hprt1_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lns.T.notable_hprt1_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference<br />Sequences</th><th id="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_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_000194.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000194<wbr style="display:inline-block"></wbr>.3</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000185.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000185<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.143G>A</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg48His</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most common <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is HRH; mild neurologic impairment may be present (HND).</td></tr><tr><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.151C>T</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg51Ter</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">LND <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> expected due to enzyme activity <2%</td></tr><tr><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.289_290delGT</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frameshift</td></tr><tr><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.508C>T</td><td headers="hd_h_lns.T.notable_hprt1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg170Ter</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">HND = <i>HPRT1-</i>related neurologic dysfunction; HRH = <i>HPRT1-</i>related hyperuricemia; LND = Lesch-Nyhan disease</p></div></dd><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the author. <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></dl></div></div></div></div></div><div id="lns.Chapter_Notes"><h2 id="_lns_Chapter_Notes_">Chapter Notes</h2><div id="lns.Author_Notes"><h3>Author Notes</h3><p>Dr Jinnah is Professor of Neurology and Human Genetics with more than 20 years of experience in research on and clinical management of Lesch-Nyhan disease and its milder variants. He has an NIH-funded laboratory program devoted to developing a better understanding of the abnormalities in brain function that lead to the neurobehavioral aspects of the disease, and has conducted numerous experimental clinical trials.</p></div><div id="lns.Author_History"><h3>Author History</h3><p>James C Harris, MD; Johns Hopkins University (2000-2020)<br />Hyder A Jinnah, MD, PhD (2000-present)<br />Janice A Nicklas, PhD; University of Vermont (2000-2007)<br />William L Nyhan, MD, PhD; University of California, San Diego (2000-2020)<br />J Patrick O'Neill, PhD; University of Vermont (2000-2020)</p></div><div id="lns.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>6 August 2020 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>15 May 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>10 June 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 January 2009 (cd) Revision: <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> available clinically</div></li><li class="half_rhythm"><div>27 November 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>8 February 2005 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 February 2003 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 September 2000 (me) Review posted live</div></li><li class="half_rhythm"><div>20 March 2000 (jn) Original submission</div></li></ul></div></div><div id="lns.References"><h2 id="_lns_References_">References</h2><div id="lns.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="lns.REF.cakmakli.2019.353">Cakmakli HF, Torres RJ, Menendez A, Yalcin-Cakmakli G, Porter CC, Puig JG, Jinnah HA. Macrocytic anemia in Lesch-Nyhan disease and its variants. <span><span class="ref-journal">Genet Med. </span>2019;<span class="ref-vol">21</span>:353–60.</span> [<a href="/pmc/articles/PMC6281870/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6281870</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29875418" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29875418</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.ceballospicot.2013.268">Ceballos-Picot I, Auge F, Fu R, Olivier-Bandini A, Cahu J, Chabrol B, Aral B, de Martinville B, Lecain JP, Jinnah HA. Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase. <span><span class="ref-journal">Mol Genet Metab. </span>2013;<span class="ref-vol">110</span>:268–74.</span> [<a href="/pmc/articles/PMC3830450/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3830450</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24075303" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24075303</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.cotton.2018.25">Cotton AC, Bell RB, Jinnah HA. Expert opinion vs patient perspective in treatment of rare disorders: tooth extraction in Lesch-Nyhan disease as an example. <span><span class="ref-journal">JIMD Rep. </span>2018;<span class="ref-vol">41</span>:25–7.</span> [<a href="/pmc/articles/PMC6122048/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6122048</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29243037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29243037</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.de_gregorio.2005.70">De Gregorio L, Jinnah HA, Harris JC, Nyhan WL, Schretlen DJ, Trombley LM, O'Neill JP. Lesch-Nyhan disease in a female with a clinically normal monozygotic twin. <span><span class="ref-journal">Mol Genet Metab. </span>2005;<span class="ref-vol">85</span>:70–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15862283" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15862283</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.fu.2014.1282">Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA, et al. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. <span><span class="ref-journal">Brain. </span>2014;<span class="ref-vol">137</span>:1282–303.</span> [<a href="/pmc/articles/PMC3999711/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3999711</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23975452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23975452</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.fu.2015.55">Fu R, Sutcliffe D, Zhao H, Huang X, Schretlen DJ, Benkovic S, Jinnah HA. Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways. <span><span class="ref-journal">Mol Genet Metab. </span>2015;<span class="ref-vol">114</span>:55–61.</span> [<a href="/pmc/articles/PMC4277921/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4277921</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25481104" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25481104</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.g_ttle.2014.95">Göttle M, Prudente CN, Fu R, Sutcliffe D, Pang H, Cooper D, Veledar E, Glass JD, Gearing M, Visser JE, Jinnah HA. Loss of neurotransmitter phenotype among midbrain dopamine neurons in Lesch-Nyhan disease. <span><span class="ref-journal">Ann Neurol. </span>2014;<span class="ref-vol">76</span>:95–107.</span> [<a href="/pmc/articles/PMC4827147/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4827147</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24891139" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24891139</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.jinnah.2010.671">Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Laróvere LE, Chen C-J, Cossu A, Wu Ch-H, Sampat R, Chang S-J, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG. Attenuated variants of Lesch-Nyhan disease. <span><span class="ref-journal">Brain. </span>2010;<span class="ref-vol">133</span>:671–89.</span> [<a href="/pmc/articles/PMC2842514/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2842514</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20176575" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20176575</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.jinnah.2006.1201">Jinnah HA, Visser JE, Harris JC, Verdu A, Larovere L, Ceballos-Picot I, Gonzalez-Alegre P, Neychev V, Torres RJ, Dulac O, Desguerre I, Schretlen DJ, Robey KL, Barabas G, Bloem BR, Nyhan W, De Kremer R, Eddey GE, Puig JG, Reich SG. Delineation of the motor disorder of Lesch-Nyhan disease. <span><span class="ref-journal">Brain. </span>2006;<span class="ref-vol">129</span>:1201–17.</span> [<a href="/pmc/articles/PMC3508431/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3508431</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16549399" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16549399</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.leemanmarkowski.2018">Leeman-Markowski BA, Jinnah HA. Lesch-Nyhan disease and epilepsy. In: Pearl PL, ed. <em>Inherited Metabolic Epilepsies</em>. 2 ed. New York, NY: Demos Medical Publishing LLC; 2018:371-93.</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.madeo.2019.147">Madeo A, Di Rocco M, Brassier A, Bahi-Buisson N, De Lonlay P, Ceballos-Picot I. Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency. <span><span class="ref-journal">Mol Genet Metab. </span>2019;<span class="ref-vol">127</span>:147–57.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31182398" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31182398</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.neychev.2006.923">Neychev VK, Jinnah HA. Sudden death in Lesch-Nyhan disease. <span><span class="ref-journal">Dev Med Child Neurol. </span>2006;<span class="ref-vol">48</span>:923–6.</span> [<a href="/pmc/articles/PMC3507438/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3507438</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17044962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17044962</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.nyhan.2003.807">Nyhan WL, Vuong LU, Broock R. Prenatal diagnosis of Lesch-Nyhan disease. <span><span class="ref-journal">Prenat Diagn. </span>2003;<span class="ref-vol">23</span>:807–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14558024" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14558024</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.olson.2000.202">Olson L, Houlihan D. A review of behavioral treatments used for Lesch-Nyhan syndrome. <span><span class="ref-journal">Behav Modif. </span>2000;<span class="ref-vol">24</span>:202–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10804680" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10804680</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.puig.1998.950">Puig JG, Mateos FA, Torres RJ, Buno AS. Purine metabolism in female heterozygotes for hypoxanthine-guanine phosphoribosyltransferase deficiency. <span><span class="ref-journal">Eur J Clin Invest. </span>1998;<span class="ref-vol">28</span>:950–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9824441" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9824441</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.robey.2003.167">Robey KL, Reck JF, Giacomini KD, Barabas G, Eddey GE. Modes and patterns of self-mutilation in persons with Lesch-Nyhan disease. <span><span class="ref-journal">Dev Med Child Neurol. </span>2003;<span class="ref-vol">45</span>:167–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12613772" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12613772</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.sampat.2011.71">Sampat R, Fu R, Larovere LE, Torres RJ, Ceballos-Picot I, Fischbach M, de Kremer R, Schretlen DJ, Puig JG, Jinnah HA. Mechanisms for phenotypic variation in Lesch-Nyhan disease and its variants. <span><span class="ref-journal">Hum Genet. </span>2011;<span class="ref-vol">129</span>:71–8.</span> [<a href="/pmc/articles/PMC3034646/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3034646</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20981450" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20981450</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.schretlen.2001.805">Schretlen DJ, Harris JC, Park KS, Jinnah HA, del Pozo NO. Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency. <span><span class="ref-journal">J Int Neuropsychol Soc. </span>2001;<span class="ref-vol">7</span>:805–12.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11771623" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11771623</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.schretlen.2013.1151">Schretlen DJ, Varvaris M, Ho TE, Vannorsdall TD, Gordon B, Harris JC, Jinnah HA. Regional brain abnormalities in Lesch-Nyhan disease and its variants: a cross-sectional analysis. <span><span class="ref-journal">Lancet Neurol. </span>2013;<span class="ref-vol">12</span>:1151–8.</span> [<a href="/pmc/articles/PMC3932536/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3932536</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24383089" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24383089</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.schretlen.2005.673">Schretlen DJ, Ward J, Meyer SM, Yun J, Puig JG, Nyhan WL, Jinnah HA, Harris JC. Behavioral aspects of Lesch-Nyhan disease and its variants. <span><span class="ref-journal">Dev Med Child Neurol. </span>2005;<span class="ref-vol">47</span>:673–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16174310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16174310</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.visser.2000.449">Visser JE, Baer PR, Jinnah HA. Lesch-Nyhan syndrome and the basal ganglia. <span><span class="ref-journal">Brain Res Rev. </span>2000;<span class="ref-vol">32</span>:449–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10760551" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10760551</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="lns.REF.willers.2004.737">Willers I. Germline mosaicism complicates molecular diagnosis of Lesch-Nyhan syndrome. <span><span class="ref-journal">Prenat Diagn. </span>2004;<span class="ref-vol">24</span>:737–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15386453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15386453</span></a>]</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/NBK1149/?report=reader">PubReader</a></li><li><a href="/books/NBK1149/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1149" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1149" style="display:none" title="Cite this Page"><div class="bk_tt">Jinnah HA. HPRT1 Disorders. 2000 Sep 25 [Updated 2020 Aug 6]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. 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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=medgen&DbFrom=books&Cmd=Link&LinkName=books_medgen&IdsFromResult=1488526" ref="log$=recordlinks">MedGen</a><div class="brieflinkpop offscreen_noflow">Related information in MedGen</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=1488526" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=1488526" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=1488526" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=1488526" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301668" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24006547" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lichter-Konecki U, Caldovic L, Morizono H, Simpson K, Ah Mew N, MacLeod E. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301734" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phosphoribosylpyrophosphate Synthetase Superactivity.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phosphoribosylpyrophosphate Synthetase Superactivity.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">de Brouwer APM, Christodoulou J. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301578" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24278995" 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