publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/300322

4331 lines
363 KiB
Text
Raw Permalink Blame History

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
<head>
<!--
################################# CRAWLER WARNING #################################
- The terms of service and the robots.txt file disallows crawling of this site,
please see https://omim.org/help/agreement for more information.
- A number of data files are available for download at https://omim.org/downloads.
- We have an API which you can learn about at https://omim.org/help/api and register
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
- You should feel free to contact us at https://omim.org/contact to figure out the best
approach to getting the data you need for your work.
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
DISTRIBUTED CRAWLS OF THIS SITE.
################################# CRAWLER WARNING #################################
-->
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
<meta http-equiv="cache-control" content="no-cache" />
<meta http-equiv="pragma" content="no-cache" />
<meta name="robots" content="index, follow" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
contain copious links to other genetics resources." />
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
<meta name="theme-color" content="#333333" />
<link rel="icon" href="/static/omim/favicon.png" />
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
<link rel="manifest" href="/static/omim/manifest.json" />
<script id='mimBrowserCapability'>
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
</script>
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
<link rel="preconnect" href="https://www.googletagmanager.com" />
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag(){window.dataLayer.push(arguments);}
gtag("js", new Date());
gtag("config", "G-HMPSQC23JJ");
</script>
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
<div id="mimBootstrapDeviceSize">
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
</div>
<title>
Entry
- #300322 - LESCH-NYHAN SYNDROME; LNS
- OMIM
</title>
</head>
<body>
<div id="mimBody">
<div id="mimHeader" class="hidden-print">
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
<div class="container-fluid">
<!-- Brand and toggle get grouped for better mobile display -->
<div class="navbar-header">
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
<span class="sr-only"> Toggle navigation </span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
</button>
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
</div>
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
<ul class="nav navbar-nav">
<li>
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
</li>
<li class="dropdown">
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
<li>
<a href="/statistics/update"> Update List </a>
</li>
<li>
<a href="/statistics/entry"> Entry Statistics </a>
</li>
<li>
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
</li>
<li>
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
<li>
<a href="/downloads/"> Register for Downloads </a>
</li>
<li>
<a href="/api"> Register for API Access </a>
</li>
</ul>
</li>
<li>
<a href="/contact?mimNumber=300322"><span class="mim-navbar-menu-font"> Contact Us </span></a>
</li>
<li>
<a href="/mimmatch/">
<span class="mim-navbar-menu-font">
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
MIMmatch
</span>
</span>
</a>
</li>
<li class="dropdown">
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
<li>
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
</li>
<li>
<a href="/donors"> Donors </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
<li>
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/search"> Search Help </a>
</li>
<li>
<a href="/help/linking"> Linking Help </a>
</li>
<li>
<a href="/help/api"> API Help </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/external"> External Links </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/agreement"> Use Agreement </a>
</li>
<li>
<a href="/help/copyright"> Copyright </a>
</li>
</ul>
</li>
<li>
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
</li>
</ul>
</div>
</div>
</nav>
</div>
<div id="mimSearch" class="hidden-print">
<div class="container">
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
<input type="hidden" id="mimSearchStart" name="start" value="1" />
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
<div class="row">
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
<div class="form-group">
<div class="input-group">
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
<div class="input-group-btn">
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
<ul class="dropdown-menu dropdown-menu-right">
<li class="dropdown-header">
Advanced Search
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/entry"> OMIM </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/geneMap"> Gene Map </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/history"> Search History </a>
</li>
</ul>
</div>
</div>
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
</div>
</div>
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
<span class="small">
</span>
</div>
</div>
</form>
<div class="row">
<p />
</div>
</div>
</div>
<!-- <div id="mimSearch"> -->
<div id="mimContent">
<div class="container hidden-print">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<div id="mimAlertBanner">
</div>
</div>
</div>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
<div id="mimFloatingTocMenu" class="small" role="navigation">
<p>
<span class="h4">#300322</span>
<br />
<strong>Table of Contents</strong>
</p>
<nav>
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
<li role="presentation">
<a href="#title"><strong>Title</strong></a>
</li>
<li role="presentation">
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
</li>
<li role="presentation">
<a href="/clinicalSynopsis/300322"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#history">History</a>
</li>
<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">External Links</div>
</div>
</a>
</h4>
</div>
</div>
<div id="mimExternalLinksFold" class="collapse in">
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=LESCH-NYHAN SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=197&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1149/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/4181" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300322[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=510" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/654bc17a-802e-4450-95d9-7b52313618a7/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:1919" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/300322" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA002855/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:1919" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:300322" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 10406007<br />
<strong>ICD10CM:</strong> E79.1<br />
<strong>ORPHA:</strong> 510<br />
<strong>DO:</strong> 1919<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
300322
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
LESCH-NYHAN SYNDROME; LNS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1 DEFICIENCY<br />
HPRT1 DEFICIENCY<br />
HPRT DEFICIENCY<br />
HPRT DEFICIENCY, COMPLETE
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
HPRT DEFICIENCY, NEUROLOGIC VARIANT, INCLUDED
</span>
</div>
<div>
<span class="h4 mim-font">
LESCH-NYHAN SYNDROME, NEUROLOGIC VARIANT, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/697?start=-3&limit=10&highlight=697">
Xq26.2-q26.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Lesch-Nyhan syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300322"> 300322 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
HPRT1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/308000"> 308000 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/300322" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/300322" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/300322" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- X-linked recessive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845977</a>, <a href="https://bioportal.bioontology.org/search?q=C1279481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279481</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Growth retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59576002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59576002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444896005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444896005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Testicular atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17585008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17585008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N50.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N50.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/608.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">608.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0156312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0156312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000029" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000029</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000029" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000029</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Nephrolithiasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95570007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95570007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N20.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N20.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/592.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">592.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000787" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000787</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000787" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000787</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Gout <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90560007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90560007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M10</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M10.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M10.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/274.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">274.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">274</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018099&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018099</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001997</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001997</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Uric acid tophi <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806613&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806613</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Motor delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/307653008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">307653008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57187006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57187006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F82</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a>, <a href="https://bioportal.bioontology.org/search?q=C0520947&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0520947</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br /> -
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Self-injurious behavior, median onset age 2 years <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845894&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845894</a>]</span><br /> -
Extrapyramidal signs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43378000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43378000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234133</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span><br /> -
Choreoathetosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43105007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43105007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085583</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span><br /> -
Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
Basal ganglia dysfunction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845895&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845895</a>]</span><br /> -
Spasticity, hyperreflexia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845896&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845896</a>]</span><br /> -
Opisthotonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8652009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8652009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002179</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002179</a>]</span><br /> -
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br /> -
Mental retardation (IQ 45-75) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845897&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845897</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271737000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271737000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D64.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D64.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/285.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">285.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002871</a>, <a href="https://bioportal.bioontology.org/search?q=C1000483&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1000483</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001903" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001903</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001903" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001903</a>]</span><br /> -
Megaloblastic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53165003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53165003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D53.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D53.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001889</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001889</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hyperuricemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35885006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35885006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740394</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002149</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002149</a>]</span><br /> -
Hyperuricosuria <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R82.993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R82.993</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0948643&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0948643</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003149</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003149</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Classic Lesch-Nyhan, < 1.5% hypoxanthine phosphoribosyltransferase (HPRT) activity<br /> -
Variant Lesch-Nyhan, 1.5-8% HPRT activity with neurologic abnormalities, but no self-injurious behavior<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the hypoxanthine phosphoribosyltransferase gene (HPRT1, <a href="/entry/308000#0004">308000.0004</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because Lesch-Nyhan syndrome (LNS) is caused by mutation in the HPRT gene (<a href="/entry/308000">308000</a>), which encodes hypoxanthine guanine phosphoribosyltransferase, on chromosome Xq26.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>The features of Lesch-Nyhan syndrome (LNS) are intellectual disability, spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive biting of fingers and lips. Megaloblastic anemia has been found in some patients (summary by <a href="#41" class="mim-tip-reference" title="van der Zee, S. P. M., Schretlen, E. D. A. M., Monnens, L. A. H. &lt;strong&gt;Megaloblastic anaemia in the Lesch-Nyhan syndrome. (Letter)&lt;/strong&gt; Lancet 291: 1427 only, 1968. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4173010/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4173010&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(68)92002-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4173010">van der Zee et al., 1968</a>, <a href="#24" class="mim-tip-reference" title="Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I. &lt;strong&gt;Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.&lt;/strong&gt; Molec. Genet. Metab. 127: 147-157, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31182398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31182398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.06.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31182398">Madeo et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4173010+31182398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>Virtually complete deficiency of HPRT residual activity (less than 1.5%) is associated with the Lesch-Nyhan syndrome, whereas partial deficiency (at least 8%) is associated with HPRT-related hyperuricemia (HRH; <a href="/entry/300323">300323</a>), also known as Kelley-Seegmiller syndrome. LNS is characterized by abnormal metabolic and neurologic manifestations. In contrast, Kelley-Seegmiller syndrome is usually associated only with the clinical manifestations of excessive purine production. Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. After puberty, the hyperuricemia in Kelley-Seegmiller syndrome may cause gout. A third group of patients, with 1.5 to 8% of HPRT activity, is associated with a neurologic variant of LNS, with uric acid overproduction and neurologic disability that varies from minor clumsiness to debilitating extrapyramidal and pyramidal motor dysfunction (<a href="#20" class="mim-tip-reference" title="Jinnah, H. A., Friedmann, T. &lt;strong&gt;Lesch-Nyhan disease and its variants. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic &amp; Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. P. 2537."None>Jinnah and Friedmann, 2001</a>).</p><p><a href="#2" class="mim-tip-reference" title="Bakay, B., Nissinen, E., Sweetman, L., Francke, U., Nyhan, W. L. &lt;strong&gt;Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome.&lt;/strong&gt; Pediat. Res. 13: 1365-1370, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/523196/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;523196&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197912000-00013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="523196">Bakay et al. (1979)</a> restudied a patient with HPRT deficiency, choreoathetosis, spasticity, dysarthria, and hyperuricemia, but normal intelligence and no self-mutilation. (A maternal uncle had been identically affected.) Although HPRT deficiency seemed to be complete, cultured fibroblasts had some capacity for metabolism of hypoxanthine and guanine. <a href="#32" class="mim-tip-reference" title="Page, T., Nyhan, W. L., Morena de Vega, V. &lt;strong&gt;Syndrome of mild mental retardation, spastic gait, and skeletal malformations in a family with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.&lt;/strong&gt; Pediatrics 79: 713-717, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3575027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3575027&lt;/a&gt;]" pmid="3575027">Page et al. (1987)</a> described 2 brothers and 2 of their maternal uncles who had HPRT deficiency as the cause of mild mental retardation, spastic gait, and pyramidal tract sign. They were, furthermore, short of stature with proximally placed thumbs and fifth finger clinodactyly. Activity of the enzyme was virtually zero in lysates of red cells or hair roots, but in intact fibroblasts the level of activity was 7.5% of normal. Kinetic studies also demonstrated differences. A sister of the brothers was, by enzyme assay, heterozygous. One of the affected uncles had advanced tophaceous gout by age 32 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=523196+3575027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
<a href="#18" class="mim-tip-reference" title="Hladnik, U., Nyhan, W. L., Bertelli, M. &lt;strong&gt;Variable expression of HPRT deficiency in 5 members of a family with the same mutation.&lt;/strong&gt; Arch. Neurol. 65: 1240-1243, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18779430/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18779430&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.65.9.1240&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18779430">Hladnik et al. (2008)</a> reported a family in which 5 individuals carrying the same splice site mutation in the HPRT gene showed marked phenotypic variability resulting from HPRT deficiency. One patient had classic Lesch-Nyhan syndrome with delayed development, spasticity, dystonia, and self-injurious behavior. Two patients had an intermediate phenotype with mild cognitive and learning difficulties, dystonia, and increased uric acid, but no self-injurious behavior, and 2 had mild spasticity, gout, and normal IQ. <a href="#18" class="mim-tip-reference" title="Hladnik, U., Nyhan, W. L., Bertelli, M. &lt;strong&gt;Variable expression of HPRT deficiency in 5 members of a family with the same mutation.&lt;/strong&gt; Arch. Neurol. 65: 1240-1243, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18779430/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18779430&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.65.9.1240&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18779430">Hladnik et al. (2008)</a> postulated that each individual had various expression of the mutant and wildtype transcript, and emphasized that individuals with the same genotype may not necessarily have the identical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18779430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Sarafoglou, K., Grosse-Redlinger, K., Boys, C. J., Charnas, L., Otten, N., Broock, R., Nyhan, W. L. &lt;strong&gt;Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.&lt;/strong&gt; Arch. Neurol. 67: 761-764, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20558399/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20558399&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2010.116&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20558399">Sarafoglou et al. (2010)</a> reported a 3-generation family in which 3 individuals carrying the same missense mutation in the HPRT1 gene showed phenotypic variability. The proband presented at age 14.5 months with increased uric acid levels and later showed mildly delayed development. His cousin was diagnosed at age 26 months, and had mild generalized hypotonia, delayed motor development, focal dystonia of the lower limbs, and mild developmental impairment with speech delay. The boys' 65-year-old grandfather was more severely affected, with borderline cognitive function, severe dyslexia, spasticity, and flexion contractures leading to motor impairment. He had a long history of gout, nephrolithiasis, and progressive renal dysfunction. Medical history revealed that his symptoms had been attributed to cerebral palsy due to perinatal asphyxia. Enzymatic studies of cultured fibroblasts showed decreased activity in the proband, more severely decreased activity in the cousin, and the most severely decreased activity in the grandfather, consistent with their phenotypes. Cells from the grandfather grew more slowly than those from the grandchildren and appeared less robust. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20558399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I. &lt;strong&gt;Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.&lt;/strong&gt; Molec. Genet. Metab. 127: 147-157, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31182398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31182398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.06.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31182398">Madeo et al. (2019)</a> described clinical features in 101 French and Italian patients with HPRT mutations, including 66 with LNS, 22 with the LNS neurologic variant (which the authors called HPRT-related neurologic dysfunction; HND), and 13 with HRH. The clinical manifestations at disease onset were nonspecific, but orange discoloration in the diaper was reported in 22% of patients. Neurologic involvement was overall more severe in LNS than in HND. The median age of presentation of involuntary movements and self-injurious behavior in LNS was 1.0 and 3 years, respectively. At least one epileptic episode was reported in approximately 13% of patients with LNS and HND. Of the approximately 40% of LNS patients and 30% of HND patients who had an MRI, a quarter of the LNS patients had variable abnormalities, the most frequent being mild to moderate brain atrophy, and all HND patients had normal findings. Language delay was common in LNS and HND, but the majority of HND patients could speak in complex sentences whereas the majority of LNS patients could speak in simple sentences or speak single words. Language comprehension was generally preserved. Approximately 60% of patients with HND had cognitive impairment. Renal disease, seen in approximately 66% of patients, occurred with a median onset age of 1.1 years. Six patients (2 with LNS, 2 with HND and 2 with HRH) developed chronic renal failure. In 3 cases, renal failure was a consequence of chronic lithiasis, and in 2 patients renal failure was secondary to focal segmental glomerulosclerosis and nephrotic syndrome. Two patients underwent kidney transplantation. Gout, seen in approximately 26% of patients, occurred with a median age of onset of 18 years and was more frequent in HND and HRH than in LNS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31182398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="biochemicalFeatures" class="mim-anchor"></a>
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>A 200-fold increase in the conversion of C(14)-labeled glycine to uric acid was observed by <a href="#29" class="mim-tip-reference" title="Nyhan, W. L., Oliver, W. J., Lesch, M. &lt;strong&gt;A familial disorder of uric acid metabolism and central nervous system function. II.&lt;/strong&gt; J. Pediat. 67: 257-263, 1965."None>Nyhan et al. (1965)</a>. <a href="#37" class="mim-tip-reference" title="Seegmiller, J. E., Rosenbloom, F. M., Kelley, W. N. &lt;strong&gt;Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis.&lt;/strong&gt; Science 155: 1682-1684, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6020292/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6020292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.155.3770.1682&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6020292">Seegmiller et al. (1967)</a> demonstrated deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). That the enzyme deficiency resulted in excessive purine synthesis suggested that the enzyme (or the product of its function) normally plays a controlling role in purine metabolism. Resistance to 8-azaguanine in cultured diploid human fibroblasts was induced by x-ray in pioneer experiments (<a href="#1" class="mim-tip-reference" title="Albertini, R. J., DeMars, R. &lt;strong&gt;Somatic cell mutation: detection and quantification of x-ray-induced mutation in cultured, diploid human fibroblasts.&lt;/strong&gt; Mutat. Res. 18: 199-224, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4711931/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4711931&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0027-5107(73)90037-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4711931">Albertini and DeMars, 1973</a>). Mutation in the HPRT gene is the basis for this resistance. Lesch-Nyhan cells are resistant to 8-azaguanine. <a href="#40" class="mim-tip-reference" title="Upchurch, K. S., Leyva, A., Arnold, W. J., Holmes, E. W., Kelley, W. N. &lt;strong&gt;Hypoxanthine phosphoribosyltransferase deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein.&lt;/strong&gt; Proc. Nat. Acad. Sci. 72: 4142-4146, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1060094/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1060094&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.72.10.4142&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1060094">Upchurch et al. (1975)</a> found a normal amount of cross-reacting material in 1 of 12 patients with HPRT deficiency. The others had less than 3% of the normal amount. <a href="#13" class="mim-tip-reference" title="Ghangas, G. S., Milman, G. &lt;strong&gt;Radioimmune determination of hypoxanthine phosphoribosyltransferase crossreacting material in erythrocytes of Lesch-Nyhan patients.&lt;/strong&gt; Proc. Nat. Acad. Sci. 72: 4147-4150, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1060095/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1060095&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.72.10.4147&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1060095">Ghangas and Milman (1975)</a> confirmed this by another method. <a href="#43" class="mim-tip-reference" title="Wilson, J. M., Stout, J. T., Palella, T. D., Davidson, B. L., Kelley, W. N., Caskey, C. T. &lt;strong&gt;A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man.&lt;/strong&gt; J. Clin. Invest. 77: 188-195, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3944251/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3944251&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI112275&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3944251">Wilson et al. (1986)</a> analyzed cell lines of 24 patients with HPRT deficiency at the levels of residual protein, mRNA, and DNA. At least 16 patients had unique mutations of the HPRT gene. Most cell lines had normal quantities of mRNA but undetectable quantities of enzyme. Eight of the patients retained significant quantities of structurally altered but functionally abnormal HPRT enzyme variants. A minority of patients lacked both enzyme and mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1060094+6020292+1060095+3944251+4711931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Fu, R., Sutcliffe, D., Zhao, H., Huang, X., Schretlen, D. J., Benkovic, S., Jinnah, H. A. &lt;strong&gt;Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways.&lt;/strong&gt; Molec. Genet. Metab. 114: 55-61, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25481104/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25481104&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25481104[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2014.11.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25481104">Fu et al. (2015)</a> created fibroblast cultures for 21 healthy controls and 36 patients with a broad spectrum of disease severity, including Lesch-Nyhan syndrome, related to HPRT deficiency. The authors assessed hypoxanthine recycling, guanine recycling, steady-state purine pools, and de novo purine synthesis. There was a strong correlation between disease severity and either hypoxanthine or guanine recycling. Intracellular purines were normal in the HPRT-deficient fibroblasts, but purine wasting was evident as increased purine metabolites excreted from cells. The normal intracellular purines in the HPRT-deficient fibroblasts were likely due in part to a compensatory increase in purine synthesis, as demonstrated by a significant increase in purinosomes. However, the increase in purine synthesis did not appear to correlate with disease severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25481104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>There is variable disease severity in patients with Lesch-Nyhan syndrome, with an inverse relationship between HPRT1 enzyme activity measured in intact cells and clinical severity. Patients with classic Lesch-Nyhan disease, the most severe and frequent form, have the lowest HPRT enzyme activity (less than 1.5% of normal) in intact cultured fibroblasts. Patients with partial HPRT deficiency, designated as Lesch-Nyhan variants, have HPRT1 enzyme activity ranging from 1.5 to 8.0%. Individuals with an intermediate variant form known as the 'neurologic variant' are neurologically indistinguishable from patients with Lesch-Nyhan disease, but they do not have self-injurious behaviors and intelligence is normal or near-normal. The least-affected patients with the variant form have residual HPRT1 enzyme activity exceeding 8%; their only manifestations are attributed to hyperuricemia, and include gout, hematuria, and nephrolithiasis (summary by <a href="#36" class="mim-tip-reference" title="Sarafoglou, K., Grosse-Redlinger, K., Boys, C. J., Charnas, L., Otten, N., Broock, R., Nyhan, W. L. &lt;strong&gt;Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.&lt;/strong&gt; Arch. Neurol. 67: 761-764, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20558399/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20558399&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2010.116&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20558399">Sarafoglou et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20558399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalManagement" class="mim-anchor"></a>
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#24" class="mim-tip-reference" title="Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I. &lt;strong&gt;Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.&lt;/strong&gt; Molec. Genet. Metab. 127: 147-157, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31182398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31182398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.06.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31182398">Madeo et al. (2019)</a> reported the results of treatment in 67 French and Italian patients with LNS (51 patients) or the LNS neurologic variant (16 patients). Although none of the drugs used for neurologic involvement and behavioral abnormalities were fully effective, some therapies were associated with limited clinical improvement. Botulinum toxin and baclofen were partially beneficial for the control of dystonia. Gabapentin was partially efficacious for dystonia and self-injurious behavior in the 13 patients who received it. Among the 12 patients with LNS who were treated with levodopa, one half reported a partial benefit for dystonia and behavior. The average age of patients who improved with levodopa was 3.2 years, whereas the average age of the patients who did not improve was 9.0 years, suggesting improved efficacy with earlier administration. Tetrabenazine was associated with improvement of dystonia in most of the 6 patients to whom it was administered. <a href="#24" class="mim-tip-reference" title="Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I. &lt;strong&gt;Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.&lt;/strong&gt; Molec. Genet. Metab. 127: 147-157, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31182398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31182398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.06.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31182398">Madeo et al. (2019)</a> also described results of treatment for renal and joint symptoms in these patients as well as in 9 patients with HRH. Fifty-four patients had improvement with allopurinol treatment, but allopurinol was interrupted in 9.3% of cases due to lack of efficacy or appearance of xanthine stones. Febuxostat was the most frequent alternative therapy. Half of patients received urinary alkalinizing agents. Three patients with persistent uric acid lithiasis and 1 patient with severe gout who were not responsive to standard treatment responded to treatment with recombinant urate oxidase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31182398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>X-linkage was first suggested by <a href="#19" class="mim-tip-reference" title="Hoefnagel, D., Andrew, E. D., Mireault, N. G., Berndt, W. O. &lt;strong&gt;Hereditary choreoathetosis, self-mutilation and hyperuricemia in young males.&lt;/strong&gt; New Eng. J. Med. 273: 130-135, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14303658/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14303658&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196507152730303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14303658">Hoefnagel et al. (1965)</a> and was supported by a rapidly accumulated series of families with deficiency of HPRT. <a href="#34" class="mim-tip-reference" title="Rosenbloom, F. M., Kelley, W. N., Henderson, J. F., Seegmiller, J. E. &lt;strong&gt;Lyon hypothesis and X-linked disease. (Letter)&lt;/strong&gt; Lancet 290: 305-306, 1967. Note: Originally Volume II."None>Rosenbloom et al. (1967)</a> and <a href="#25" class="mim-tip-reference" title="Migeon, B. R., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J., Childs, B. &lt;strong&gt;X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations.&lt;/strong&gt; Science 160: 425-427, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4868511/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4868511&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.160.3826.425&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4868511">Migeon et al. (1968)</a> demonstrated 2 populations of fibroblasts, as regards the relevant enzyme activity, in heterozygous females, thus providing support both for X-linkage and for the Lyon hypothesis. Studies using human-mouse somatic cell hybrids indicate, by reasoning similar to that used for locating the thymidine kinase locus to chromosome 17 (<a href="/entry/188300">188300</a>), that the HPRT locus is on the X chromosome (<a href="#27" class="mim-tip-reference" title="Nabholz, M., Miggiano, V., Bodmer, W. &lt;strong&gt;Genetic analysis with human-mouse somatic cell hybrids.&lt;/strong&gt; Nature 223: 358-363, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4309885/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4309885&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/223358a0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4309885">Nabholz et al., 1969</a>). Mosaicism can be demonstrated by study of hair roots in women heterozygous for the Lesch-Nyhan syndrome (<a href="#38" class="mim-tip-reference" title="Silvers, D. N., Cox, R. P., Balis, M. E., Dancis, J. &lt;strong&gt;Detection of the heterozygote in Lesch-Nyhan disease by hair-root analysis.&lt;/strong&gt; New Eng. J. Med. 286: 390-395, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4333083/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4333083&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197202242860802&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4333083">Silvers et al., 1972</a>). <a href="#8" class="mim-tip-reference" title="Francke, U., Felsenstein, J., Gartler, S. M., Migeon, B. R., Dancis, J., Seegmiller, J. E., Bakay, B., Nyhan, W. L. &lt;strong&gt;The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.&lt;/strong&gt; Am. J. Hum. Genet. 28: 123-137, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1266847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1266847&lt;/a&gt;]" pmid="1266847">Francke et al. (1976)</a> studied the frequency of new mutations among affected males. The Lesch-Nyhan syndrome is particularly favorable for this purpose because no affected males reproduce, the diagnosis is unequivocal and cases come readily to attention, and particularly because heterozygosity can be demonstrated in females by the existence of 2 populations of cultured fibroblasts. There were few new mutations, contrary to the expected one-third. On the other hand, about one-half of heterozygous females were new mutations, as is predicted by theory. The finding may indicate a higher frequency of mutation in males than in females. Another possibility is the role of somatic and half-chromatid mutations (<a href="#12" class="mim-tip-reference" title="Gartler, S. M., Francke, U. &lt;strong&gt;Half-chromatid mutation: transmission in humans?&lt;/strong&gt; Am. J. Hum. Genet. 27: 218-223, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1124765/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1124765&lt;/a&gt;]" pmid="1124765">Gartler and Francke, 1975</a>). New mutation cases of heterozygous females had elevated parental age. <a href="#42" class="mim-tip-reference" title="Vogel, F. &lt;strong&gt;A probable sex difference in some mutation rates. (Editorial)&lt;/strong&gt; Am. J. Hum. Genet. 29: 312-319, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/868880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;868880&lt;/a&gt;]" pmid="868880">Vogel (1977)</a> reviewed the evidence concerning hemophilia and the Lesch-Nyhan syndrome leading to the conclusion that the mutation rate is higher in males than in females. Evidence that the mutation rate for the Lesch-Nyhan disease may be higher in males than in females was reviewed by <a href="#8" class="mim-tip-reference" title="Francke, U., Felsenstein, J., Gartler, S. M., Migeon, B. R., Dancis, J., Seegmiller, J. E., Bakay, B., Nyhan, W. L. &lt;strong&gt;The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.&lt;/strong&gt; Am. J. Hum. Genet. 28: 123-137, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1266847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1266847&lt;/a&gt;]" pmid="1266847">Francke et al. (1976)</a> and criticized by <a href="#26" class="mim-tip-reference" title="Morton, N. E., Lalouel, J. M. &lt;strong&gt;Genetic epidemiology of Lesch-Nyhan disease. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 29: 304-307, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/868879/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;868879&lt;/a&gt;]" pmid="868879">Morton and Lalouel (1977)</a>. <a href="#9" class="mim-tip-reference" title="Francke, U., Felsenstein, J., Gartler, S. M., Nyhan, W. L., Seegmiller, J. E. &lt;strong&gt;Answer to criticism of Morton and Lalouel. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 29: 307-310, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17948539/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17948539&lt;/a&gt;]" pmid="17948539">Francke et al. (1977)</a> answered the criticism. <a href="#39" class="mim-tip-reference" title="Strauss, G. H., Allen, E. F., Albertini, R. J. &lt;strong&gt;An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan mutation.&lt;/strong&gt; Biochem. Genet. 18: 529-547, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7437011/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7437011&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00484400&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7437011">Strauss et al. (1980)</a> showed that females heterozygous for the Lesch-Nyhan mutation have 2 populations of peripheral blood lymphocytes with regard to sensitivity to 6-thioguanine inhibition of tritiated thymidine incorporation following phytohemagglutinin stimulation. <a href="#17" class="mim-tip-reference" title="Henderson, J. F., Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E. &lt;strong&gt;Inheritance of purine phosphoribosyltransferases in man.&lt;/strong&gt; Am. J. Hum. Genet. 21: 61-70, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5763607/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5763607&lt;/a&gt;]" pmid="5763607">Henderson et al. (1969)</a> concluded that the locus for HPRT is closely linked to the Xg (<a href="/entry/314700">314700</a>) locus; <a href="#16" class="mim-tip-reference" title="Greene, M. L., Nyhan, W. L., Seegmiller, J. E. &lt;strong&gt;Hypoxanthine-guanine phosphoribosyltransferase deficiency and Xg blood group.&lt;/strong&gt; Am. J. Hum. Genet. 22: 50-54, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5411648/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5411648&lt;/a&gt;]" pmid="5411648">Greene et al. (1970)</a> concluded, however, that the HPRT and Xg loci 'are sufficient distance from each other on the human X chromosome that linkage cannot be detected.' <a href="#28" class="mim-tip-reference" title="Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F., Keele, D. K. &lt;strong&gt;Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 65: 214-218, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5263751/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5263751&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.65.1.214&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5263751">Nyhan et al. (1970)</a> observed a sibship in which both HPRT deficiency and G6PD deficiency (<a href="/entry/300908">300908</a>) were segregating and found 2 of 4 recombinants. <a href="#28" class="mim-tip-reference" title="Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F., Keele, D. K. &lt;strong&gt;Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 65: 214-218, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5263751/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5263751&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.65.1.214&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5263751">Nyhan et al. (1970)</a> also found that heterozygotes had normal levels of HPRT in red cells. They interpreted this as indicating a selective advantage of G6PD-normal over G6PD-deficient cells. (In adrenoleukodystrophy (<a href="/entry/300100">300100</a>), it is the mutant cell that enjoys the selective advantage.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14303658+1124765+4309885+4333083+5411648+868879+1266847+5763607+17948539+4868511+868880+7437011+5263751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Yukawa, T., Akazawa, H., Miyake, Y., Takahashi, Y., Nagao, H., Takeda, E. &lt;strong&gt;A female patient with Lesch-Nyhan syndrome.&lt;/strong&gt; Dev. Med. Child Neurol. 34: 543-546, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1612215/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1612215&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-8749.1992.tb11477.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1612215">Yukawa et al. (1992)</a> described a seemingly typical case of Lesch-Nyhan syndrome in a female with a normal karyotype. The parents were nonconsanguineous. In addition to unusual lyonization, uniparental disomy is a possible explanation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1612215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="pathogenesis" class="mim-anchor"></a>
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><strong><em>Pathogenesis of Mental Retardation and Self-injurious Behavior</em></strong></p><p>
<a href="#44" class="mim-tip-reference" title="Wong, D. F., Harris, J. C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R. F., Ravert, H. T., Yaster, M., Evans, A., Rousset, O., Bryan, R. N., Gjedde, A., Kuhar, M. J., Breese, G. R. &lt;strong&gt;Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.&lt;/strong&gt; Proc. Nat. Acad. Sci. 93: 5539-5543, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8643611/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8643611&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.93.11.5539&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8643611">Wong et al. (1996)</a> discussed 3 lines of evidence that had suggested that HPRT deficiency is associated with abnormal dopamine (DA) function in LNS: (1) an autopsy study of 3 LNS subjects demonstrated a marked reduction in the DA content and in the activity of DNA-synthesizing enzymes in the caudate and putamen (<a href="#23" class="mim-tip-reference" title="Lloyd, K. G., Hornykiewicz, O., Davidson, L., Shannak, K., Farley, I., Goldstein, M., Shibuya, M., Kelley, W. N., Fox, I. H. &lt;strong&gt;Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.&lt;/strong&gt; New Eng. J. Med. 305: 1106-1111, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6117011/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6117011&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198111053051902&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6117011">Lloyd et al., 1981</a>); (2) when neonatal rats are depleted of DA with the neurotoxin 6-hydroxydopamine, self-injurious behavior, similar to that seen in LNS, occurred when the rats were challenged with 3,4-dihydroxyphenylalanine (L-DOPA) as adults (<a href="#4" class="mim-tip-reference" title="Breese, G. R., Criswell, H. E., Duncan, G. E., Mueller, R. A. &lt;strong&gt;A dopamine deficiency model of Lesch-Nyhan disease: the neonatal-6-OHDA-lesioned rat.&lt;/strong&gt; Brain Res. Bull. 25: 477-484, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2127238/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2127238&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0361-9230(90)90240-z&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2127238">Breese et al., 1990</a>); and (3) in an HPRT-deficient mutant mouse strain, there is a reduction of striatal tyrosine hydroxylase and in the number of striatal dopamine transporters (<a href="#21" class="mim-tip-reference" title="Jinnah, H. A., Wojcik, B. E., Hunt, M., Narang, N., Lee, K. Y., Goldstein, M., Wamsley, J. K., Langlais, P. J., Friedmann, T. &lt;strong&gt;Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.&lt;/strong&gt; J. Neurosci. 14: 1164-1174, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7509865/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7509865&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1523/JNEUROSCI.14-03-01164.1994&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7509865">Jinnah et al., 1994</a>). To establish that DA deficiency is present in LNS, <a href="#44" class="mim-tip-reference" title="Wong, D. F., Harris, J. C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R. F., Ravert, H. T., Yaster, M., Evans, A., Rousset, O., Bryan, R. N., Gjedde, A., Kuhar, M. J., Breese, G. R. &lt;strong&gt;Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.&lt;/strong&gt; Proc. Nat. Acad. Sci. 93: 5539-5543, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8643611/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8643611&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.93.11.5539&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8643611">Wong et al. (1996)</a> used a ligand that binds to DA transporters to estimate the density of DA-containing neurons in the caudate and putamen of 6 subjects with classic LNS. They made comparisons with 10 control subjects and 3 patients with Rett syndrome (<a href="/entry/312750">312750</a>). Depending on the method of analysis, a 50 to 63% reduction of the binding to DA transporters in the caudate and a 64 to 75% reduction in the putamen of LNS patients was observed compared to the normal control group; similar reductions were found between Rett syndrome and LNS patients. Volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LNS patients. To ensure that a reduction in the caudate volume would not confound the results, <a href="#44" class="mim-tip-reference" title="Wong, D. F., Harris, J. C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R. F., Ravert, H. T., Yaster, M., Evans, A., Rousset, O., Bryan, R. N., Gjedde, A., Kuhar, M. J., Breese, G. R. &lt;strong&gt;Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.&lt;/strong&gt; Proc. Nat. Acad. Sci. 93: 5539-5543, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8643611/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8643611&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.93.11.5539&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8643611">Wong et al. (1996)</a> performed a rigorous partial volume correction of the caudate time activity curve. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LNS patients when contrasted to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8643611+7509865+6117011+2127238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ernst, M., Zametkin, A. J., Matochik, J. A., Pascualvaca, D., Jons, P. H., Hardy, K., Hankerson, J. G., Doudet, D. J., Cohen, R. M. &lt;strong&gt;Presynaptic dopaminergic deficits in Lesch-Nyhan disease.&lt;/strong&gt; New Eng. J. Med. 334: 1568-1572, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8628337/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8628337&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199606133342403&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8628337">Ernst et al. (1996)</a> concluded that patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggested that they contribute to the characteristic neuropsychiatric manifestations of the disease. These studies were done with positron-emission tomography (PET) with the tracer fluorodopa-F18. This tracer, an analog of dopa, is a large, neutral amino acid that is transported into presynaptic neurons, where it is converted by the enzyme dopa decarboxylase (<a href="/entry/107930">107930</a>) into fluorodopamine F18, which subsequently enters catecholamine-storage vesicles. Hence, data obtained with the use of fluorodopa-F18 and PET reflect dopa decarboxylase activity and dopamine-storage processes. In an accompanying editorial, <a href="#30" class="mim-tip-reference" title="Nyhan, W. L., Wong, D. F. &lt;strong&gt;New approaches to understanding Lesch-Nyhan disease. (Editorial)&lt;/strong&gt; New Eng. J. Med. 334: 1602-1604, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8628345/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8628345&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199606133342411&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8628345">Nyhan and Wong (1996)</a> commented on the new findings and reviewed the normal function of HPRT with a diagram. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8628337+8628345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Ceballos-Picot, I., Mockel, L., Potier, M.-C., Dauphinot, L., Shirley, T. L., Torero-Ibad, R., Fuchs, J., Jinnah, H. A. &lt;strong&gt;Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.&lt;/strong&gt; Hum. Molec. Genet. 18: 2317-2327, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19342420/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19342420&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19342420[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp164&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19342420">Ceballos-Picot et al. (2009)</a> demonstrated that HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype. Microarray methods and quantitative PCR were applied to 10 different HPRT-deficient sublines derived from the hybrid MN9D cell line, derived from somatic fusion of embryonic mouse primary midbrain dopaminergic neurons with a mouse neuroblastoma line. There were consistent increases in mRNAs for engrailed-1 (EN1; <a href="/entry/131290">131290</a>) and -2 (EN2; <a href="/entry/131310">131310</a>), transcription factors known to play a role in the specification and survival of dopamine neurons. The increases in mRNAs were accompanied by increases in engrailed proteins, and restoration of HPRT reverted engrailed expression towards normal levels. The functional relevance of the abnormal developmental molecular signature of the HPRT-deficient MN9D cells was evident in impoverished neurite outgrowth when the cells were forced to differentiate chemically. These abnormalities were also seen in HPRT-deficient sublines from the SK-N-BE(2)-M17 human neuroblastoma line, and overexpression of engrailed was documented in primary fibroblasts from patients with Lesch-Nyhan disease. <a href="#5" class="mim-tip-reference" title="Ceballos-Picot, I., Mockel, L., Potier, M.-C., Dauphinot, L., Shirley, T. L., Torero-Ibad, R., Fuchs, J., Jinnah, H. A. &lt;strong&gt;Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.&lt;/strong&gt; Hum. Molec. Genet. 18: 2317-2327, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19342420/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19342420&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19342420[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp164&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19342420">Ceballos-Picot et al. (2009)</a> concluded that HPRT deficiency may affect dopaminergic neurons by influencing early developmental mechanisms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19342420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Cristini, S., Navone, S., Canzi, L., Acerbi, F., Ciusani, E., Hladnik, U., de Gemmis, P., Alessandri, G., Colombo, A., Parati, E., Invernici, G. &lt;strong&gt;Human neural stem cells: a model system for the study of Lesch-Nyhan disease neurological aspects.&lt;/strong&gt; Hum. Molec. Genet. 19: 1939-1950, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20159777/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20159777&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddq072&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20159777">Cristini et al. (2010)</a> examined the effect of HPRT deficiency on the differentiation of neurons in human neural stem cells (NSCs) isolated from human Lesch-Nyhan disease fetal brain. LNS NSCs demonstrated aberrant expression of several transcription factors and DA markers, and HPRT-deficient dopaminergic neurons demonstrated a striking deficit in neurite outgrowth. Exposure of the LNS NSCs to retinoic acid medium elicited the generation of dopaminergic neurons. The authors concluded that neurogenesis is aberrant in LNS NSCs and suggested a role for HPRT in neurodevelopment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20159777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
<a href="#11" class="mim-tip-reference" title="Fujimoto, W. Y., Seegmiller, J. E., Uhlendorf, B. W., Jacobson, C. B. &lt;strong&gt;Biochemical diagnosis of X-linked disease in utero. (Letter)&lt;/strong&gt; Lancet 292: 511-512, 1968. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4174524/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4174524&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(68)90671-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4174524">Fujimoto et al. (1968)</a> presented evidence that the disease can be recognized in the fetus well before 20 weeks, i.e., within the limit for elective abortion. The method used was an autoradiographic test for HPRT activity, applied to cells obtained by amniocentesis. <a href="#3" class="mim-tip-reference" title="Boyle, J. A., Raivio, K. O., Astrin, K. H., Shulman, J. D., Graf, M. L., Seegmiller, J. E., Jacobson, C. B. &lt;strong&gt;Lesch-Nyhan syndrome: preventive control by prenatal diagnosis.&lt;/strong&gt; Science 169: 688-689, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5464303/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5464303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.169.3946.688&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5464303">Boyle et al. (1970)</a> made the prenatal diagnosis and performed therapeutic abortion. <a href="#14" class="mim-tip-reference" title="Gibbs, D. A., McFadyen, I. R., Crawfurd, M. d&#x27;A., de Muinck Keizer, E. E., Headhouse-Benson, C. M., Wilson, T. M., Farrant, P. H. &lt;strong&gt;First-trimester diagnosis of Lesch-Nyhan syndrome.&lt;/strong&gt; Lancet 324: 1180-1183, 1984. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6150236/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6150236&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(84)92743-0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6150236">Gibbs et al. (1984)</a> showed that by ultramicroassay of HPRT it is possible to diagnose the Lesch-Nyhan syndrome on the basis of chorionic villi sampled at 8-9 weeks of gestation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5464303+4174524+6150236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Graham, G. W., Aitken, D. A., Connor, J. M. &lt;strong&gt;Prenatal diagnosis by enzyme analysis in 15 pregnancies at risk for the Lesch-Nyhan syndrome.&lt;/strong&gt; Prenatal Diag. 16: 647-651, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8843475/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8843475&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1097-0223(199607)16:7&lt;647::AID-PD932&gt;3.0.CO;2-S&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8843475">Graham et al. (1996)</a> investigated 15 pregnancies at risk for Lesch-Nyhan syndrome between 8 and 17 weeks' gestation by measurement of HPRT and APRT (<a href="/entry/102600">102600</a>) enzyme activities in chorionic villus samples (cultured and uncultured) or in cultured amniotic fluid cells. Ten pregnancies had normal enzyme levels and a normal outcome, while a further 2 predicted to be normal miscarried later in the pregnancy. Three pregnancies had low levels of residual HPRT activity in chorionic villi. Comparable levels of residual activity in the index case in 2 pregnancies and in cells from the abortus in the third case confirmed that the pregnancies were indeed affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8843475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>For a discussion of the molecular defects involved in Lesch-Nyhan syndrome, see the HPRT1 gene (<a href="/entry/308000">308000</a>).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#24" class="mim-tip-reference" title="Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I. &lt;strong&gt;Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.&lt;/strong&gt; Molec. Genet. Metab. 127: 147-157, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31182398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31182398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.06.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31182398">Madeo et al. (2019)</a> described the association between HPRT mutations and clinical findings in 76 French and Italian patients, including 52 with LNS from 47 families, 19 with the LNS neurologic variant from 12 families, and 12 with HPRT-related hyperuricemia (HRH) from 6 families. They found that overall, patients with missense mutations had significantly later onset of disease and less frequent neurologic manifestations or self-injurious behavior compared to patients with other mutation types including nonsense, deletion, splicing, or complex gene rearrangements. Mutation type was not associated with the development of gout or nephropathy. Intrafamilial phenotypic variability was seen in a few families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31182398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="history" class="mim-anchor"></a>
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#22" class="mim-tip-reference" title="Lesch, M., Nyhan, W. L. &lt;strong&gt;A familial disorder of uric acid metabolism and central nervous system function.&lt;/strong&gt; Am. J. Med. 36: 561-570, 1964.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14142409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14142409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(64)90104-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14142409">Lesch and Nyhan (1964)</a> described the disorder that bears their names on the basis of 2 brothers. <a href="#31" class="mim-tip-reference" title="Nyhan, W. L. &lt;strong&gt;The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 171-178, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9211189/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9211189&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005348504512&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9211189">Nyhan (1997)</a> gave an account of the recognition of the syndrome as an inborn error of purine metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14142409+9211189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Preston, R. &lt;strong&gt;An error in the code.&lt;/strong&gt; New Yorker August 13: 30-36, 2007."None>Preston (2007)</a> provided a popular description of the discovery of the disorder and what the study of a rare disorder such as this can tell us about human behavior.</p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Rosenbloom1967" class="mim-tip-reference" title="Rosenbloom, F. M., Kelley, W. N., Miller, J., Henderson, J. F., Seegmiller, J. E. &lt;strong&gt;Inherited disorder of purine metabolism: correlation between central nervous system dysfunction and biochemical defects.&lt;/strong&gt; JAMA 202: 175-177, 1967.">Rosenbloom et al. (1967)</a>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Albertini1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Albertini, R. J., DeMars, R.
<strong>Somatic cell mutation: detection and quantification of x-ray-induced mutation in cultured, diploid human fibroblasts.</strong>
Mutat. Res. 18: 199-224, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4711931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4711931</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4711931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0027-5107(73)90037-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Bakay1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bakay, B., Nissinen, E., Sweetman, L., Francke, U., Nyhan, W. L.
<strong>Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome.</strong>
Pediat. Res. 13: 1365-1370, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/523196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">523196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=523196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-197912000-00013" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Boyle1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Boyle, J. A., Raivio, K. O., Astrin, K. H., Shulman, J. D., Graf, M. L., Seegmiller, J. E., Jacobson, C. B.
<strong>Lesch-Nyhan syndrome: preventive control by prenatal diagnosis.</strong>
Science 169: 688-689, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5464303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5464303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5464303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.169.3946.688" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Breese1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Breese, G. R., Criswell, H. E., Duncan, G. E., Mueller, R. A.
<strong>A dopamine deficiency model of Lesch-Nyhan disease: the neonatal-6-OHDA-lesioned rat.</strong>
Brain Res. Bull. 25: 477-484, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2127238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2127238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2127238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0361-9230(90)90240-z" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Ceballos-Picot2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ceballos-Picot, I., Mockel, L., Potier, M.-C., Dauphinot, L., Shirley, T. L., Torero-Ibad, R., Fuchs, J., Jinnah, H. A.
<strong>Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.</strong>
Hum. Molec. Genet. 18: 2317-2327, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342420</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342420[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19342420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddp164" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Cristini2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cristini, S., Navone, S., Canzi, L., Acerbi, F., Ciusani, E., Hladnik, U., de Gemmis, P., Alessandri, G., Colombo, A., Parati, E., Invernici, G.
<strong>Human neural stem cells: a model system for the study of Lesch-Nyhan disease neurological aspects.</strong>
Hum. Molec. Genet. 19: 1939-1950, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20159777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20159777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20159777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddq072" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Ernst1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ernst, M., Zametkin, A. J., Matochik, J. A., Pascualvaca, D., Jons, P. H., Hardy, K., Hankerson, J. G., Doudet, D. J., Cohen, R. M.
<strong>Presynaptic dopaminergic deficits in Lesch-Nyhan disease.</strong>
New Eng. J. Med. 334: 1568-1572, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8628337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8628337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8628337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199606133342403" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Francke1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Francke, U., Felsenstein, J., Gartler, S. M., Migeon, B. R., Dancis, J., Seegmiller, J. E., Bakay, B., Nyhan, W. L.
<strong>The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.</strong>
Am. J. Hum. Genet. 28: 123-137, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1266847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1266847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1266847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Francke1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Francke, U., Felsenstein, J., Gartler, S. M., Nyhan, W. L., Seegmiller, J. E.
<strong>Answer to criticism of Morton and Lalouel. (Letter)</strong>
Am. J. Hum. Genet. 29: 307-310, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17948539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17948539</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17948539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Fu2015" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fu, R., Sutcliffe, D., Zhao, H., Huang, X., Schretlen, D. J., Benkovic, S., Jinnah, H. A.
<strong>Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways.</strong>
Molec. Genet. Metab. 114: 55-61, 2015.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25481104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25481104</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25481104[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25481104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2014.11.001" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Fujimoto1968" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fujimoto, W. Y., Seegmiller, J. E., Uhlendorf, B. W., Jacobson, C. B.
<strong>Biochemical diagnosis of X-linked disease in utero. (Letter)</strong>
Lancet 292: 511-512, 1968. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4174524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4174524</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4174524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(68)90671-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Gartler1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gartler, S. M., Francke, U.
<strong>Half-chromatid mutation: transmission in humans?</strong>
Am. J. Hum. Genet. 27: 218-223, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1124765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1124765</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1124765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Ghangas1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ghangas, G. S., Milman, G.
<strong>Radioimmune determination of hypoxanthine phosphoribosyltransferase crossreacting material in erythrocytes of Lesch-Nyhan patients.</strong>
Proc. Nat. Acad. Sci. 72: 4147-4150, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1060095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1060095</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1060095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.72.10.4147" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Gibbs1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbs, D. A., McFadyen, I. R., Crawfurd, M. d'A., de Muinck Keizer, E. E., Headhouse-Benson, C. M., Wilson, T. M., Farrant, P. H.
<strong>First-trimester diagnosis of Lesch-Nyhan syndrome.</strong>
Lancet 324: 1180-1183, 1984. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6150236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6150236</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6150236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(84)92743-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Graham1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Graham, G. W., Aitken, D. A., Connor, J. M.
<strong>Prenatal diagnosis by enzyme analysis in 15 pregnancies at risk for the Lesch-Nyhan syndrome.</strong>
Prenatal Diag. 16: 647-651, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8843475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8843475</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8843475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1097-0223(199607)16:7&lt;647::AID-PD932&gt;3.0.CO;2-S" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Greene1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Greene, M. L., Nyhan, W. L., Seegmiller, J. E.
<strong>Hypoxanthine-guanine phosphoribosyltransferase deficiency and Xg blood group.</strong>
Am. J. Hum. Genet. 22: 50-54, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5411648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5411648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5411648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Henderson1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Henderson, J. F., Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E.
<strong>Inheritance of purine phosphoribosyltransferases in man.</strong>
Am. J. Hum. Genet. 21: 61-70, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5763607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5763607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5763607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Hladnik2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hladnik, U., Nyhan, W. L., Bertelli, M.
<strong>Variable expression of HPRT deficiency in 5 members of a family with the same mutation.</strong>
Arch. Neurol. 65: 1240-1243, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18779430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18779430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18779430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.65.9.1240" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Hoefnagel1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hoefnagel, D., Andrew, E. D., Mireault, N. G., Berndt, W. O.
<strong>Hereditary choreoathetosis, self-mutilation and hyperuricemia in young males.</strong>
New Eng. J. Med. 273: 130-135, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14303658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14303658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14303658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM196507152730303" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Jinnah2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jinnah, H. A., Friedmann, T.
<strong>Lesch-Nyhan disease and its variants. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic & Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. P. 2537.
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Jinnah1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jinnah, H. A., Wojcik, B. E., Hunt, M., Narang, N., Lee, K. Y., Goldstein, M., Wamsley, J. K., Langlais, P. J., Friedmann, T.
<strong>Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.</strong>
J. Neurosci. 14: 1164-1174, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7509865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1523/JNEUROSCI.14-03-01164.1994" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Lesch1964" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lesch, M., Nyhan, W. L.
<strong>A familial disorder of uric acid metabolism and central nervous system function.</strong>
Am. J. Med. 36: 561-570, 1964.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14142409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14142409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14142409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9343(64)90104-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Lloyd1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lloyd, K. G., Hornykiewicz, O., Davidson, L., Shannak, K., Farley, I., Goldstein, M., Shibuya, M., Kelley, W. N., Fox, I. H.
<strong>Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.</strong>
New Eng. J. Med. 305: 1106-1111, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6117011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6117011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6117011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198111053051902" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Madeo2019" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I.
<strong>Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.</strong>
Molec. Genet. Metab. 127: 147-157, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31182398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31182398</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31182398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2019.06.001" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Migeon1968" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Migeon, B. R., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J., Childs, B.
<strong>X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations.</strong>
Science 160: 425-427, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4868511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4868511</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4868511" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.160.3826.425" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Morton1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morton, N. E., Lalouel, J. M.
<strong>Genetic epidemiology of Lesch-Nyhan disease. (Letter)</strong>
Am. J. Hum. Genet. 29: 304-307, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/868879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">868879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=868879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Nabholz1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nabholz, M., Miggiano, V., Bodmer, W.
<strong>Genetic analysis with human-mouse somatic cell hybrids.</strong>
Nature 223: 358-363, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4309885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4309885</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4309885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/223358a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Nyhan1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F., Keele, D. K.
<strong>Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome.</strong>
Proc. Nat. Acad. Sci. 65: 214-218, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5263751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5263751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5263751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.65.1.214" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Nyhan1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nyhan, W. L., Oliver, W. J., Lesch, M.
<strong>A familial disorder of uric acid metabolism and central nervous system function. II.</strong>
J. Pediat. 67: 257-263, 1965.
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Nyhan1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nyhan, W. L., Wong, D. F.
<strong>New approaches to understanding Lesch-Nyhan disease. (Editorial)</strong>
New Eng. J. Med. 334: 1602-1604, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8628345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8628345</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8628345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199606133342411" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Nyhan1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nyhan, W. L.
<strong>The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism.</strong>
J. Inherit. Metab. Dis. 20: 171-178, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9211189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9211189</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9211189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1005348504512" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Page1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Page, T., Nyhan, W. L., Morena de Vega, V.
<strong>Syndrome of mild mental retardation, spastic gait, and skeletal malformations in a family with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.</strong>
Pediatrics 79: 713-717, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3575027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3575027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3575027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Preston2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Preston, R.
<strong>An error in the code.</strong>
New Yorker August 13: 30-36, 2007.
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Rosenbloom1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rosenbloom, F. M., Kelley, W. N., Henderson, J. F., Seegmiller, J. E.
<strong>Lyon hypothesis and X-linked disease. (Letter)</strong>
Lancet 290: 305-306, 1967. Note: Originally Volume II.
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Rosenbloom1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rosenbloom, F. M., Kelley, W. N., Miller, J., Henderson, J. F., Seegmiller, J. E.
<strong>Inherited disorder of purine metabolism: correlation between central nervous system dysfunction and biochemical defects.</strong>
JAMA 202: 175-177, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6072350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6072350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6072350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/jama.202.3.175" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Sarafoglou2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sarafoglou, K., Grosse-Redlinger, K., Boys, C. J., Charnas, L., Otten, N., Broock, R., Nyhan, W. L.
<strong>Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.</strong>
Arch. Neurol. 67: 761-764, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20558399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20558399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20558399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneurol.2010.116" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Seegmiller1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Seegmiller, J. E., Rosenbloom, F. M., Kelley, W. N.
<strong>Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis.</strong>
Science 155: 1682-1684, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6020292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6020292</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6020292" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.155.3770.1682" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Silvers1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Silvers, D. N., Cox, R. P., Balis, M. E., Dancis, J.
<strong>Detection of the heterozygote in Lesch-Nyhan disease by hair-root analysis.</strong>
New Eng. J. Med. 286: 390-395, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4333083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4333083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4333083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197202242860802" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Strauss1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Strauss, G. H., Allen, E. F., Albertini, R. J.
<strong>An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan mutation.</strong>
Biochem. Genet. 18: 529-547, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7437011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7437011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7437011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00484400" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Upchurch1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Upchurch, K. S., Leyva, A., Arnold, W. J., Holmes, E. W., Kelley, W. N.
<strong>Hypoxanthine phosphoribosyltransferase deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein.</strong>
Proc. Nat. Acad. Sci. 72: 4142-4146, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1060094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1060094</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1060094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.72.10.4142" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="van der Zee1968" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van der Zee, S. P. M., Schretlen, E. D. A. M., Monnens, L. A. H.
<strong>Megaloblastic anaemia in the Lesch-Nyhan syndrome. (Letter)</strong>
Lancet 291: 1427 only, 1968. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4173010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4173010</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4173010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(68)92002-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Vogel1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Vogel, F.
<strong>A probable sex difference in some mutation rates. (Editorial)</strong>
Am. J. Hum. Genet. 29: 312-319, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/868880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">868880</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=868880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Wilson1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilson, J. M., Stout, J. T., Palella, T. D., Davidson, B. L., Kelley, W. N., Caskey, C. T.
<strong>A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man.</strong>
J. Clin. Invest. 77: 188-195, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3944251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3944251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3944251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI112275" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Wong1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wong, D. F., Harris, J. C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R. F., Ravert, H. T., Yaster, M., Evans, A., Rousset, O., Bryan, R. N., Gjedde, A., Kuhar, M. J., Breese, G. R.
<strong>Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.</strong>
Proc. Nat. Acad. Sci. 93: 5539-5543, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643611</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8643611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.93.11.5539" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Yukawa1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yukawa, T., Akazawa, H., Miyake, Y., Takahashi, Y., Nagao, H., Takeda, E.
<strong>A female patient with Lesch-Nyhan syndrome.</strong>
Dev. Med. Child Neurol. 34: 543-546, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1612215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1612215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1612215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1469-8749.1992.tb11477.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 09/09/2020
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 2/26/2015<br>George E. Tiller - updated : 8/14/2013<br>Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Victor A. McKusick - updated : 8/10/2007
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh : 4/4/2001
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 11/01/2022
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 11/01/2022<br>carol : 09/11/2020<br>carol : 09/10/2020<br>carol : 09/09/2020<br>carol : 09/01/2017<br>carol : 08/31/2017<br>joanna : 08/30/2017<br>carol : 07/09/2016<br>alopez : 2/26/2015<br>mcolton : 2/24/2014<br>carol : 10/24/2013<br>carol : 8/16/2013<br>tpirozzi : 8/15/2013<br>tpirozzi : 8/14/2013<br>wwang : 7/26/2011<br>ckniffin : 7/21/2011<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>terry : 6/3/2009<br>wwang : 4/13/2009<br>ckniffin : 4/6/2009<br>terry : 3/27/2009<br>carol : 8/10/2007<br>terry : 8/10/2007<br>joanna : 4/9/2003<br>carol : 4/11/2001<br>mcapotos : 4/6/2001<br>carol : 4/5/2001<br>carol : 4/5/2001<br>carol : 4/4/2001<br>carol : 4/4/2001
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 300322
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
LESCH-NYHAN SYNDROME; LNS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1 DEFICIENCY<br />
HPRT1 DEFICIENCY<br />
HPRT DEFICIENCY<br />
HPRT DEFICIENCY, COMPLETE
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
HPRT DEFICIENCY, NEUROLOGIC VARIANT, INCLUDED
</span>
</div>
<div>
<span class="h4 mim-font">
LESCH-NYHAN SYNDROME, NEUROLOGIC VARIANT, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 10406007; &nbsp;
<strong>ICD10CM:</strong> E79.1; &nbsp;
<strong>ORPHA:</strong> 510; &nbsp;
<strong>DO:</strong> 1919; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
Xq26.2-q26.3
</span>
</td>
<td>
<span class="mim-font">
Lesch-Nyhan syndrome
</span>
</td>
<td>
<span class="mim-font">
300322
</span>
</td>
<td>
<span class="mim-font">
X-linked recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
HPRT1
</span>
</td>
<td>
<span class="mim-font">
308000
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because Lesch-Nyhan syndrome (LNS) is caused by mutation in the HPRT gene (308000), which encodes hypoxanthine guanine phosphoribosyltransferase, on chromosome Xq26.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The features of Lesch-Nyhan syndrome (LNS) are intellectual disability, spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive biting of fingers and lips. Megaloblastic anemia has been found in some patients (summary by van der Zee et al., 1968, Madeo et al., 2019). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Virtually complete deficiency of HPRT residual activity (less than 1.5%) is associated with the Lesch-Nyhan syndrome, whereas partial deficiency (at least 8%) is associated with HPRT-related hyperuricemia (HRH; 300323), also known as Kelley-Seegmiller syndrome. LNS is characterized by abnormal metabolic and neurologic manifestations. In contrast, Kelley-Seegmiller syndrome is usually associated only with the clinical manifestations of excessive purine production. Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. After puberty, the hyperuricemia in Kelley-Seegmiller syndrome may cause gout. A third group of patients, with 1.5 to 8% of HPRT activity, is associated with a neurologic variant of LNS, with uric acid overproduction and neurologic disability that varies from minor clumsiness to debilitating extrapyramidal and pyramidal motor dysfunction (Jinnah and Friedmann, 2001).</p><p>Bakay et al. (1979) restudied a patient with HPRT deficiency, choreoathetosis, spasticity, dysarthria, and hyperuricemia, but normal intelligence and no self-mutilation. (A maternal uncle had been identically affected.) Although HPRT deficiency seemed to be complete, cultured fibroblasts had some capacity for metabolism of hypoxanthine and guanine. Page et al. (1987) described 2 brothers and 2 of their maternal uncles who had HPRT deficiency as the cause of mild mental retardation, spastic gait, and pyramidal tract sign. They were, furthermore, short of stature with proximally placed thumbs and fifth finger clinodactyly. Activity of the enzyme was virtually zero in lysates of red cells or hair roots, but in intact fibroblasts the level of activity was 7.5% of normal. Kinetic studies also demonstrated differences. A sister of the brothers was, by enzyme assay, heterozygous. One of the affected uncles had advanced tophaceous gout by age 32 years. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Hladnik et al. (2008) reported a family in which 5 individuals carrying the same splice site mutation in the HPRT gene showed marked phenotypic variability resulting from HPRT deficiency. One patient had classic Lesch-Nyhan syndrome with delayed development, spasticity, dystonia, and self-injurious behavior. Two patients had an intermediate phenotype with mild cognitive and learning difficulties, dystonia, and increased uric acid, but no self-injurious behavior, and 2 had mild spasticity, gout, and normal IQ. Hladnik et al. (2008) postulated that each individual had various expression of the mutant and wildtype transcript, and emphasized that individuals with the same genotype may not necessarily have the identical phenotype. </p><p>Sarafoglou et al. (2010) reported a 3-generation family in which 3 individuals carrying the same missense mutation in the HPRT1 gene showed phenotypic variability. The proband presented at age 14.5 months with increased uric acid levels and later showed mildly delayed development. His cousin was diagnosed at age 26 months, and had mild generalized hypotonia, delayed motor development, focal dystonia of the lower limbs, and mild developmental impairment with speech delay. The boys' 65-year-old grandfather was more severely affected, with borderline cognitive function, severe dyslexia, spasticity, and flexion contractures leading to motor impairment. He had a long history of gout, nephrolithiasis, and progressive renal dysfunction. Medical history revealed that his symptoms had been attributed to cerebral palsy due to perinatal asphyxia. Enzymatic studies of cultured fibroblasts showed decreased activity in the proband, more severely decreased activity in the cousin, and the most severely decreased activity in the grandfather, consistent with their phenotypes. Cells from the grandfather grew more slowly than those from the grandchildren and appeared less robust. </p><p>Madeo et al. (2019) described clinical features in 101 French and Italian patients with HPRT mutations, including 66 with LNS, 22 with the LNS neurologic variant (which the authors called HPRT-related neurologic dysfunction; HND), and 13 with HRH. The clinical manifestations at disease onset were nonspecific, but orange discoloration in the diaper was reported in 22% of patients. Neurologic involvement was overall more severe in LNS than in HND. The median age of presentation of involuntary movements and self-injurious behavior in LNS was 1.0 and 3 years, respectively. At least one epileptic episode was reported in approximately 13% of patients with LNS and HND. Of the approximately 40% of LNS patients and 30% of HND patients who had an MRI, a quarter of the LNS patients had variable abnormalities, the most frequent being mild to moderate brain atrophy, and all HND patients had normal findings. Language delay was common in LNS and HND, but the majority of HND patients could speak in complex sentences whereas the majority of LNS patients could speak in simple sentences or speak single words. Language comprehension was generally preserved. Approximately 60% of patients with HND had cognitive impairment. Renal disease, seen in approximately 66% of patients, occurred with a median onset age of 1.1 years. Six patients (2 with LNS, 2 with HND and 2 with HRH) developed chronic renal failure. In 3 cases, renal failure was a consequence of chronic lithiasis, and in 2 patients renal failure was secondary to focal segmental glomerulosclerosis and nephrotic syndrome. Two patients underwent kidney transplantation. Gout, seen in approximately 26% of patients, occurred with a median age of onset of 18 years and was more frequent in HND and HRH than in LNS. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>A 200-fold increase in the conversion of C(14)-labeled glycine to uric acid was observed by Nyhan et al. (1965). Seegmiller et al. (1967) demonstrated deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). That the enzyme deficiency resulted in excessive purine synthesis suggested that the enzyme (or the product of its function) normally plays a controlling role in purine metabolism. Resistance to 8-azaguanine in cultured diploid human fibroblasts was induced by x-ray in pioneer experiments (Albertini and DeMars, 1973). Mutation in the HPRT gene is the basis for this resistance. Lesch-Nyhan cells are resistant to 8-azaguanine. Upchurch et al. (1975) found a normal amount of cross-reacting material in 1 of 12 patients with HPRT deficiency. The others had less than 3% of the normal amount. Ghangas and Milman (1975) confirmed this by another method. Wilson et al. (1986) analyzed cell lines of 24 patients with HPRT deficiency at the levels of residual protein, mRNA, and DNA. At least 16 patients had unique mutations of the HPRT gene. Most cell lines had normal quantities of mRNA but undetectable quantities of enzyme. Eight of the patients retained significant quantities of structurally altered but functionally abnormal HPRT enzyme variants. A minority of patients lacked both enzyme and mRNA. </p><p>Fu et al. (2015) created fibroblast cultures for 21 healthy controls and 36 patients with a broad spectrum of disease severity, including Lesch-Nyhan syndrome, related to HPRT deficiency. The authors assessed hypoxanthine recycling, guanine recycling, steady-state purine pools, and de novo purine synthesis. There was a strong correlation between disease severity and either hypoxanthine or guanine recycling. Intracellular purines were normal in the HPRT-deficient fibroblasts, but purine wasting was evident as increased purine metabolites excreted from cells. The normal intracellular purines in the HPRT-deficient fibroblasts were likely due in part to a compensatory increase in purine synthesis, as demonstrated by a significant increase in purinosomes. However, the increase in purine synthesis did not appear to correlate with disease severity. </p><p>There is variable disease severity in patients with Lesch-Nyhan syndrome, with an inverse relationship between HPRT1 enzyme activity measured in intact cells and clinical severity. Patients with classic Lesch-Nyhan disease, the most severe and frequent form, have the lowest HPRT enzyme activity (less than 1.5% of normal) in intact cultured fibroblasts. Patients with partial HPRT deficiency, designated as Lesch-Nyhan variants, have HPRT1 enzyme activity ranging from 1.5 to 8.0%. Individuals with an intermediate variant form known as the 'neurologic variant' are neurologically indistinguishable from patients with Lesch-Nyhan disease, but they do not have self-injurious behaviors and intelligence is normal or near-normal. The least-affected patients with the variant form have residual HPRT1 enzyme activity exceeding 8%; their only manifestations are attributed to hyperuricemia, and include gout, hematuria, and nephrolithiasis (summary by Sarafoglou et al., 2010). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Madeo et al. (2019) reported the results of treatment in 67 French and Italian patients with LNS (51 patients) or the LNS neurologic variant (16 patients). Although none of the drugs used for neurologic involvement and behavioral abnormalities were fully effective, some therapies were associated with limited clinical improvement. Botulinum toxin and baclofen were partially beneficial for the control of dystonia. Gabapentin was partially efficacious for dystonia and self-injurious behavior in the 13 patients who received it. Among the 12 patients with LNS who were treated with levodopa, one half reported a partial benefit for dystonia and behavior. The average age of patients who improved with levodopa was 3.2 years, whereas the average age of the patients who did not improve was 9.0 years, suggesting improved efficacy with earlier administration. Tetrabenazine was associated with improvement of dystonia in most of the 6 patients to whom it was administered. Madeo et al. (2019) also described results of treatment for renal and joint symptoms in these patients as well as in 9 patients with HRH. Fifty-four patients had improvement with allopurinol treatment, but allopurinol was interrupted in 9.3% of cases due to lack of efficacy or appearance of xanthine stones. Febuxostat was the most frequent alternative therapy. Half of patients received urinary alkalinizing agents. Three patients with persistent uric acid lithiasis and 1 patient with severe gout who were not responsive to standard treatment responded to treatment with recombinant urate oxidase. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>X-linkage was first suggested by Hoefnagel et al. (1965) and was supported by a rapidly accumulated series of families with deficiency of HPRT. Rosenbloom et al. (1967) and Migeon et al. (1968) demonstrated 2 populations of fibroblasts, as regards the relevant enzyme activity, in heterozygous females, thus providing support both for X-linkage and for the Lyon hypothesis. Studies using human-mouse somatic cell hybrids indicate, by reasoning similar to that used for locating the thymidine kinase locus to chromosome 17 (188300), that the HPRT locus is on the X chromosome (Nabholz et al., 1969). Mosaicism can be demonstrated by study of hair roots in women heterozygous for the Lesch-Nyhan syndrome (Silvers et al., 1972). Francke et al. (1976) studied the frequency of new mutations among affected males. The Lesch-Nyhan syndrome is particularly favorable for this purpose because no affected males reproduce, the diagnosis is unequivocal and cases come readily to attention, and particularly because heterozygosity can be demonstrated in females by the existence of 2 populations of cultured fibroblasts. There were few new mutations, contrary to the expected one-third. On the other hand, about one-half of heterozygous females were new mutations, as is predicted by theory. The finding may indicate a higher frequency of mutation in males than in females. Another possibility is the role of somatic and half-chromatid mutations (Gartler and Francke, 1975). New mutation cases of heterozygous females had elevated parental age. Vogel (1977) reviewed the evidence concerning hemophilia and the Lesch-Nyhan syndrome leading to the conclusion that the mutation rate is higher in males than in females. Evidence that the mutation rate for the Lesch-Nyhan disease may be higher in males than in females was reviewed by Francke et al. (1976) and criticized by Morton and Lalouel (1977). Francke et al. (1977) answered the criticism. Strauss et al. (1980) showed that females heterozygous for the Lesch-Nyhan mutation have 2 populations of peripheral blood lymphocytes with regard to sensitivity to 6-thioguanine inhibition of tritiated thymidine incorporation following phytohemagglutinin stimulation. Henderson et al. (1969) concluded that the locus for HPRT is closely linked to the Xg (314700) locus; Greene et al. (1970) concluded, however, that the HPRT and Xg loci 'are sufficient distance from each other on the human X chromosome that linkage cannot be detected.' Nyhan et al. (1970) observed a sibship in which both HPRT deficiency and G6PD deficiency (300908) were segregating and found 2 of 4 recombinants. Nyhan et al. (1970) also found that heterozygotes had normal levels of HPRT in red cells. They interpreted this as indicating a selective advantage of G6PD-normal over G6PD-deficient cells. (In adrenoleukodystrophy (300100), it is the mutant cell that enjoys the selective advantage.) </p><p>Yukawa et al. (1992) described a seemingly typical case of Lesch-Nyhan syndrome in a female with a normal karyotype. The parents were nonconsanguineous. In addition to unusual lyonization, uniparental disomy is a possible explanation. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Pathogenesis of Mental Retardation and Self-injurious Behavior</em></strong></p><p>
Wong et al. (1996) discussed 3 lines of evidence that had suggested that HPRT deficiency is associated with abnormal dopamine (DA) function in LNS: (1) an autopsy study of 3 LNS subjects demonstrated a marked reduction in the DA content and in the activity of DNA-synthesizing enzymes in the caudate and putamen (Lloyd et al., 1981); (2) when neonatal rats are depleted of DA with the neurotoxin 6-hydroxydopamine, self-injurious behavior, similar to that seen in LNS, occurred when the rats were challenged with 3,4-dihydroxyphenylalanine (L-DOPA) as adults (Breese et al., 1990); and (3) in an HPRT-deficient mutant mouse strain, there is a reduction of striatal tyrosine hydroxylase and in the number of striatal dopamine transporters (Jinnah et al., 1994). To establish that DA deficiency is present in LNS, Wong et al. (1996) used a ligand that binds to DA transporters to estimate the density of DA-containing neurons in the caudate and putamen of 6 subjects with classic LNS. They made comparisons with 10 control subjects and 3 patients with Rett syndrome (312750). Depending on the method of analysis, a 50 to 63% reduction of the binding to DA transporters in the caudate and a 64 to 75% reduction in the putamen of LNS patients was observed compared to the normal control group; similar reductions were found between Rett syndrome and LNS patients. Volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LNS patients. To ensure that a reduction in the caudate volume would not confound the results, Wong et al. (1996) performed a rigorous partial volume correction of the caudate time activity curve. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LNS patients when contrasted to controls. </p><p>Ernst et al. (1996) concluded that patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggested that they contribute to the characteristic neuropsychiatric manifestations of the disease. These studies were done with positron-emission tomography (PET) with the tracer fluorodopa-F18. This tracer, an analog of dopa, is a large, neutral amino acid that is transported into presynaptic neurons, where it is converted by the enzyme dopa decarboxylase (107930) into fluorodopamine F18, which subsequently enters catecholamine-storage vesicles. Hence, data obtained with the use of fluorodopa-F18 and PET reflect dopa decarboxylase activity and dopamine-storage processes. In an accompanying editorial, Nyhan and Wong (1996) commented on the new findings and reviewed the normal function of HPRT with a diagram. </p><p>Ceballos-Picot et al. (2009) demonstrated that HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype. Microarray methods and quantitative PCR were applied to 10 different HPRT-deficient sublines derived from the hybrid MN9D cell line, derived from somatic fusion of embryonic mouse primary midbrain dopaminergic neurons with a mouse neuroblastoma line. There were consistent increases in mRNAs for engrailed-1 (EN1; 131290) and -2 (EN2; 131310), transcription factors known to play a role in the specification and survival of dopamine neurons. The increases in mRNAs were accompanied by increases in engrailed proteins, and restoration of HPRT reverted engrailed expression towards normal levels. The functional relevance of the abnormal developmental molecular signature of the HPRT-deficient MN9D cells was evident in impoverished neurite outgrowth when the cells were forced to differentiate chemically. These abnormalities were also seen in HPRT-deficient sublines from the SK-N-BE(2)-M17 human neuroblastoma line, and overexpression of engrailed was documented in primary fibroblasts from patients with Lesch-Nyhan disease. Ceballos-Picot et al. (2009) concluded that HPRT deficiency may affect dopaminergic neurons by influencing early developmental mechanisms. </p><p>Cristini et al. (2010) examined the effect of HPRT deficiency on the differentiation of neurons in human neural stem cells (NSCs) isolated from human Lesch-Nyhan disease fetal brain. LNS NSCs demonstrated aberrant expression of several transcription factors and DA markers, and HPRT-deficient dopaminergic neurons demonstrated a striking deficit in neurite outgrowth. Exposure of the LNS NSCs to retinoic acid medium elicited the generation of dopaminergic neurons. The authors concluded that neurogenesis is aberrant in LNS NSCs and suggested a role for HPRT in neurodevelopment. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Fujimoto et al. (1968) presented evidence that the disease can be recognized in the fetus well before 20 weeks, i.e., within the limit for elective abortion. The method used was an autoradiographic test for HPRT activity, applied to cells obtained by amniocentesis. Boyle et al. (1970) made the prenatal diagnosis and performed therapeutic abortion. Gibbs et al. (1984) showed that by ultramicroassay of HPRT it is possible to diagnose the Lesch-Nyhan syndrome on the basis of chorionic villi sampled at 8-9 weeks of gestation. </p><p>Graham et al. (1996) investigated 15 pregnancies at risk for Lesch-Nyhan syndrome between 8 and 17 weeks' gestation by measurement of HPRT and APRT (102600) enzyme activities in chorionic villus samples (cultured and uncultured) or in cultured amniotic fluid cells. Ten pregnancies had normal enzyme levels and a normal outcome, while a further 2 predicted to be normal miscarried later in the pregnancy. Three pregnancies had low levels of residual HPRT activity in chorionic villi. Comparable levels of residual activity in the index case in 2 pregnancies and in cells from the abortus in the third case confirmed that the pregnancies were indeed affected. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>For a discussion of the molecular defects involved in Lesch-Nyhan syndrome, see the HPRT1 gene (308000).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Madeo et al. (2019) described the association between HPRT mutations and clinical findings in 76 French and Italian patients, including 52 with LNS from 47 families, 19 with the LNS neurologic variant from 12 families, and 12 with HPRT-related hyperuricemia (HRH) from 6 families. They found that overall, patients with missense mutations had significantly later onset of disease and less frequent neurologic manifestations or self-injurious behavior compared to patients with other mutation types including nonsense, deletion, splicing, or complex gene rearrangements. Mutation type was not associated with the development of gout or nephropathy. Intrafamilial phenotypic variability was seen in a few families. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Lesch and Nyhan (1964) described the disorder that bears their names on the basis of 2 brothers. Nyhan (1997) gave an account of the recognition of the syndrome as an inborn error of purine metabolism. </p><p>Preston (2007) provided a popular description of the discovery of the disorder and what the study of a rare disorder such as this can tell us about human behavior.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Rosenbloom et al. (1967)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Albertini, R. J., DeMars, R.
<strong>Somatic cell mutation: detection and quantification of x-ray-induced mutation in cultured, diploid human fibroblasts.</strong>
Mutat. Res. 18: 199-224, 1973.
[PubMed: 4711931]
[Full Text: https://doi.org/10.1016/0027-5107(73)90037-7]
</p>
</li>
<li>
<p class="mim-text-font">
Bakay, B., Nissinen, E., Sweetman, L., Francke, U., Nyhan, W. L.
<strong>Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome.</strong>
Pediat. Res. 13: 1365-1370, 1979.
[PubMed: 523196]
[Full Text: https://doi.org/10.1203/00006450-197912000-00013]
</p>
</li>
<li>
<p class="mim-text-font">
Boyle, J. A., Raivio, K. O., Astrin, K. H., Shulman, J. D., Graf, M. L., Seegmiller, J. E., Jacobson, C. B.
<strong>Lesch-Nyhan syndrome: preventive control by prenatal diagnosis.</strong>
Science 169: 688-689, 1970.
[PubMed: 5464303]
[Full Text: https://doi.org/10.1126/science.169.3946.688]
</p>
</li>
<li>
<p class="mim-text-font">
Breese, G. R., Criswell, H. E., Duncan, G. E., Mueller, R. A.
<strong>A dopamine deficiency model of Lesch-Nyhan disease: the neonatal-6-OHDA-lesioned rat.</strong>
Brain Res. Bull. 25: 477-484, 1990.
[PubMed: 2127238]
[Full Text: https://doi.org/10.1016/0361-9230(90)90240-z]
</p>
</li>
<li>
<p class="mim-text-font">
Ceballos-Picot, I., Mockel, L., Potier, M.-C., Dauphinot, L., Shirley, T. L., Torero-Ibad, R., Fuchs, J., Jinnah, H. A.
<strong>Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.</strong>
Hum. Molec. Genet. 18: 2317-2327, 2009.
[PubMed: 19342420]
[Full Text: https://doi.org/10.1093/hmg/ddp164]
</p>
</li>
<li>
<p class="mim-text-font">
Cristini, S., Navone, S., Canzi, L., Acerbi, F., Ciusani, E., Hladnik, U., de Gemmis, P., Alessandri, G., Colombo, A., Parati, E., Invernici, G.
<strong>Human neural stem cells: a model system for the study of Lesch-Nyhan disease neurological aspects.</strong>
Hum. Molec. Genet. 19: 1939-1950, 2010.
[PubMed: 20159777]
[Full Text: https://doi.org/10.1093/hmg/ddq072]
</p>
</li>
<li>
<p class="mim-text-font">
Ernst, M., Zametkin, A. J., Matochik, J. A., Pascualvaca, D., Jons, P. H., Hardy, K., Hankerson, J. G., Doudet, D. J., Cohen, R. M.
<strong>Presynaptic dopaminergic deficits in Lesch-Nyhan disease.</strong>
New Eng. J. Med. 334: 1568-1572, 1996.
[PubMed: 8628337]
[Full Text: https://doi.org/10.1056/NEJM199606133342403]
</p>
</li>
<li>
<p class="mim-text-font">
Francke, U., Felsenstein, J., Gartler, S. M., Migeon, B. R., Dancis, J., Seegmiller, J. E., Bakay, B., Nyhan, W. L.
<strong>The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.</strong>
Am. J. Hum. Genet. 28: 123-137, 1976.
[PubMed: 1266847]
</p>
</li>
<li>
<p class="mim-text-font">
Francke, U., Felsenstein, J., Gartler, S. M., Nyhan, W. L., Seegmiller, J. E.
<strong>Answer to criticism of Morton and Lalouel. (Letter)</strong>
Am. J. Hum. Genet. 29: 307-310, 1977.
[PubMed: 17948539]
</p>
</li>
<li>
<p class="mim-text-font">
Fu, R., Sutcliffe, D., Zhao, H., Huang, X., Schretlen, D. J., Benkovic, S., Jinnah, H. A.
<strong>Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways.</strong>
Molec. Genet. Metab. 114: 55-61, 2015.
[PubMed: 25481104]
[Full Text: https://doi.org/10.1016/j.ymgme.2014.11.001]
</p>
</li>
<li>
<p class="mim-text-font">
Fujimoto, W. Y., Seegmiller, J. E., Uhlendorf, B. W., Jacobson, C. B.
<strong>Biochemical diagnosis of X-linked disease in utero. (Letter)</strong>
Lancet 292: 511-512, 1968. Note: Originally Volume II.
[PubMed: 4174524]
[Full Text: https://doi.org/10.1016/s0140-6736(68)90671-5]
</p>
</li>
<li>
<p class="mim-text-font">
Gartler, S. M., Francke, U.
<strong>Half-chromatid mutation: transmission in humans?</strong>
Am. J. Hum. Genet. 27: 218-223, 1975.
[PubMed: 1124765]
</p>
</li>
<li>
<p class="mim-text-font">
Ghangas, G. S., Milman, G.
<strong>Radioimmune determination of hypoxanthine phosphoribosyltransferase crossreacting material in erythrocytes of Lesch-Nyhan patients.</strong>
Proc. Nat. Acad. Sci. 72: 4147-4150, 1975.
[PubMed: 1060095]
[Full Text: https://doi.org/10.1073/pnas.72.10.4147]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbs, D. A., McFadyen, I. R., Crawfurd, M. d'A., de Muinck Keizer, E. E., Headhouse-Benson, C. M., Wilson, T. M., Farrant, P. H.
<strong>First-trimester diagnosis of Lesch-Nyhan syndrome.</strong>
Lancet 324: 1180-1183, 1984. Note: Originally Volume II.
[PubMed: 6150236]
[Full Text: https://doi.org/10.1016/s0140-6736(84)92743-0]
</p>
</li>
<li>
<p class="mim-text-font">
Graham, G. W., Aitken, D. A., Connor, J. M.
<strong>Prenatal diagnosis by enzyme analysis in 15 pregnancies at risk for the Lesch-Nyhan syndrome.</strong>
Prenatal Diag. 16: 647-651, 1996.
[PubMed: 8843475]
[Full Text: https://doi.org/10.1002/(SICI)1097-0223(199607)16:7&lt;647::AID-PD932&gt;3.0.CO;2-S]
</p>
</li>
<li>
<p class="mim-text-font">
Greene, M. L., Nyhan, W. L., Seegmiller, J. E.
<strong>Hypoxanthine-guanine phosphoribosyltransferase deficiency and Xg blood group.</strong>
Am. J. Hum. Genet. 22: 50-54, 1970.
[PubMed: 5411648]
</p>
</li>
<li>
<p class="mim-text-font">
Henderson, J. F., Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E.
<strong>Inheritance of purine phosphoribosyltransferases in man.</strong>
Am. J. Hum. Genet. 21: 61-70, 1969.
[PubMed: 5763607]
</p>
</li>
<li>
<p class="mim-text-font">
Hladnik, U., Nyhan, W. L., Bertelli, M.
<strong>Variable expression of HPRT deficiency in 5 members of a family with the same mutation.</strong>
Arch. Neurol. 65: 1240-1243, 2008.
[PubMed: 18779430]
[Full Text: https://doi.org/10.1001/archneur.65.9.1240]
</p>
</li>
<li>
<p class="mim-text-font">
Hoefnagel, D., Andrew, E. D., Mireault, N. G., Berndt, W. O.
<strong>Hereditary choreoathetosis, self-mutilation and hyperuricemia in young males.</strong>
New Eng. J. Med. 273: 130-135, 1965.
[PubMed: 14303658]
[Full Text: https://doi.org/10.1056/NEJM196507152730303]
</p>
</li>
<li>
<p class="mim-text-font">
Jinnah, H. A., Friedmann, T.
<strong>Lesch-Nyhan disease and its variants. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic &amp; Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. P. 2537.
</p>
</li>
<li>
<p class="mim-text-font">
Jinnah, H. A., Wojcik, B. E., Hunt, M., Narang, N., Lee, K. Y., Goldstein, M., Wamsley, J. K., Langlais, P. J., Friedmann, T.
<strong>Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.</strong>
J. Neurosci. 14: 1164-1174, 1994.
[PubMed: 7509865]
[Full Text: https://doi.org/10.1523/JNEUROSCI.14-03-01164.1994]
</p>
</li>
<li>
<p class="mim-text-font">
Lesch, M., Nyhan, W. L.
<strong>A familial disorder of uric acid metabolism and central nervous system function.</strong>
Am. J. Med. 36: 561-570, 1964.
[PubMed: 14142409]
[Full Text: https://doi.org/10.1016/0002-9343(64)90104-4]
</p>
</li>
<li>
<p class="mim-text-font">
Lloyd, K. G., Hornykiewicz, O., Davidson, L., Shannak, K., Farley, I., Goldstein, M., Shibuya, M., Kelley, W. N., Fox, I. H.
<strong>Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.</strong>
New Eng. J. Med. 305: 1106-1111, 1981.
[PubMed: 6117011]
[Full Text: https://doi.org/10.1056/NEJM198111053051902]
</p>
</li>
<li>
<p class="mim-text-font">
Madeo, A., Di Rocco, M., Brassier, A., Bahi-Buisson, N., De Lonlay, P., Ceballos-Picot, I.
<strong>Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.</strong>
Molec. Genet. Metab. 127: 147-157, 2019.
[PubMed: 31182398]
[Full Text: https://doi.org/10.1016/j.ymgme.2019.06.001]
</p>
</li>
<li>
<p class="mim-text-font">
Migeon, B. R., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J., Childs, B.
<strong>X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations.</strong>
Science 160: 425-427, 1968.
[PubMed: 4868511]
[Full Text: https://doi.org/10.1126/science.160.3826.425]
</p>
</li>
<li>
<p class="mim-text-font">
Morton, N. E., Lalouel, J. M.
<strong>Genetic epidemiology of Lesch-Nyhan disease. (Letter)</strong>
Am. J. Hum. Genet. 29: 304-307, 1977.
[PubMed: 868879]
</p>
</li>
<li>
<p class="mim-text-font">
Nabholz, M., Miggiano, V., Bodmer, W.
<strong>Genetic analysis with human-mouse somatic cell hybrids.</strong>
Nature 223: 358-363, 1969.
[PubMed: 4309885]
[Full Text: https://doi.org/10.1038/223358a0]
</p>
</li>
<li>
<p class="mim-text-font">
Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F., Keele, D. K.
<strong>Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome.</strong>
Proc. Nat. Acad. Sci. 65: 214-218, 1970.
[PubMed: 5263751]
[Full Text: https://doi.org/10.1073/pnas.65.1.214]
</p>
</li>
<li>
<p class="mim-text-font">
Nyhan, W. L., Oliver, W. J., Lesch, M.
<strong>A familial disorder of uric acid metabolism and central nervous system function. II.</strong>
J. Pediat. 67: 257-263, 1965.
</p>
</li>
<li>
<p class="mim-text-font">
Nyhan, W. L., Wong, D. F.
<strong>New approaches to understanding Lesch-Nyhan disease. (Editorial)</strong>
New Eng. J. Med. 334: 1602-1604, 1996.
[PubMed: 8628345]
[Full Text: https://doi.org/10.1056/NEJM199606133342411]
</p>
</li>
<li>
<p class="mim-text-font">
Nyhan, W. L.
<strong>The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism.</strong>
J. Inherit. Metab. Dis. 20: 171-178, 1997.
[PubMed: 9211189]
[Full Text: https://doi.org/10.1023/a:1005348504512]
</p>
</li>
<li>
<p class="mim-text-font">
Page, T., Nyhan, W. L., Morena de Vega, V.
<strong>Syndrome of mild mental retardation, spastic gait, and skeletal malformations in a family with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.</strong>
Pediatrics 79: 713-717, 1987.
[PubMed: 3575027]
</p>
</li>
<li>
<p class="mim-text-font">
Preston, R.
<strong>An error in the code.</strong>
New Yorker August 13: 30-36, 2007.
</p>
</li>
<li>
<p class="mim-text-font">
Rosenbloom, F. M., Kelley, W. N., Henderson, J. F., Seegmiller, J. E.
<strong>Lyon hypothesis and X-linked disease. (Letter)</strong>
Lancet 290: 305-306, 1967. Note: Originally Volume II.
</p>
</li>
<li>
<p class="mim-text-font">
Rosenbloom, F. M., Kelley, W. N., Miller, J., Henderson, J. F., Seegmiller, J. E.
<strong>Inherited disorder of purine metabolism: correlation between central nervous system dysfunction and biochemical defects.</strong>
JAMA 202: 175-177, 1967.
[PubMed: 6072350]
[Full Text: https://doi.org/10.1001/jama.202.3.175]
</p>
</li>
<li>
<p class="mim-text-font">
Sarafoglou, K., Grosse-Redlinger, K., Boys, C. J., Charnas, L., Otten, N., Broock, R., Nyhan, W. L.
<strong>Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.</strong>
Arch. Neurol. 67: 761-764, 2010.
[PubMed: 20558399]
[Full Text: https://doi.org/10.1001/archneurol.2010.116]
</p>
</li>
<li>
<p class="mim-text-font">
Seegmiller, J. E., Rosenbloom, F. M., Kelley, W. N.
<strong>Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis.</strong>
Science 155: 1682-1684, 1967.
[PubMed: 6020292]
[Full Text: https://doi.org/10.1126/science.155.3770.1682]
</p>
</li>
<li>
<p class="mim-text-font">
Silvers, D. N., Cox, R. P., Balis, M. E., Dancis, J.
<strong>Detection of the heterozygote in Lesch-Nyhan disease by hair-root analysis.</strong>
New Eng. J. Med. 286: 390-395, 1972.
[PubMed: 4333083]
[Full Text: https://doi.org/10.1056/NEJM197202242860802]
</p>
</li>
<li>
<p class="mim-text-font">
Strauss, G. H., Allen, E. F., Albertini, R. J.
<strong>An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan mutation.</strong>
Biochem. Genet. 18: 529-547, 1980.
[PubMed: 7437011]
[Full Text: https://doi.org/10.1007/BF00484400]
</p>
</li>
<li>
<p class="mim-text-font">
Upchurch, K. S., Leyva, A., Arnold, W. J., Holmes, E. W., Kelley, W. N.
<strong>Hypoxanthine phosphoribosyltransferase deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein.</strong>
Proc. Nat. Acad. Sci. 72: 4142-4146, 1975.
[PubMed: 1060094]
[Full Text: https://doi.org/10.1073/pnas.72.10.4142]
</p>
</li>
<li>
<p class="mim-text-font">
van der Zee, S. P. M., Schretlen, E. D. A. M., Monnens, L. A. H.
<strong>Megaloblastic anaemia in the Lesch-Nyhan syndrome. (Letter)</strong>
Lancet 291: 1427 only, 1968. Note: Originally Volume I.
[PubMed: 4173010]
[Full Text: https://doi.org/10.1016/s0140-6736(68)92002-3]
</p>
</li>
<li>
<p class="mim-text-font">
Vogel, F.
<strong>A probable sex difference in some mutation rates. (Editorial)</strong>
Am. J. Hum. Genet. 29: 312-319, 1977.
[PubMed: 868880]
</p>
</li>
<li>
<p class="mim-text-font">
Wilson, J. M., Stout, J. T., Palella, T. D., Davidson, B. L., Kelley, W. N., Caskey, C. T.
<strong>A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man.</strong>
J. Clin. Invest. 77: 188-195, 1986.
[PubMed: 3944251]
[Full Text: https://doi.org/10.1172/JCI112275]
</p>
</li>
<li>
<p class="mim-text-font">
Wong, D. F., Harris, J. C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R. F., Ravert, H. T., Yaster, M., Evans, A., Rousset, O., Bryan, R. N., Gjedde, A., Kuhar, M. J., Breese, G. R.
<strong>Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.</strong>
Proc. Nat. Acad. Sci. 93: 5539-5543, 1996.
[PubMed: 8643611]
[Full Text: https://doi.org/10.1073/pnas.93.11.5539]
</p>
</li>
<li>
<p class="mim-text-font">
Yukawa, T., Akazawa, H., Miyake, Y., Takahashi, Y., Nagao, H., Takeda, E.
<strong>A female patient with Lesch-Nyhan syndrome.</strong>
Dev. Med. Child Neurol. 34: 543-546, 1992.
[PubMed: 1612215]
[Full Text: https://doi.org/10.1111/j.1469-8749.1992.tb11477.x]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 09/09/2020<br>Ada Hamosh - updated : 2/26/2015<br>George E. Tiller - updated : 8/14/2013<br>Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Victor A. McKusick - updated : 8/10/2007
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh : 4/4/2001
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 11/01/2022<br>alopez : 11/01/2022<br>carol : 09/11/2020<br>carol : 09/10/2020<br>carol : 09/09/2020<br>carol : 09/01/2017<br>carol : 08/31/2017<br>joanna : 08/30/2017<br>carol : 07/09/2016<br>alopez : 2/26/2015<br>mcolton : 2/24/2014<br>carol : 10/24/2013<br>carol : 8/16/2013<br>tpirozzi : 8/15/2013<br>tpirozzi : 8/14/2013<br>wwang : 7/26/2011<br>ckniffin : 7/21/2011<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>terry : 6/3/2009<br>wwang : 4/13/2009<br>ckniffin : 4/6/2009<br>terry : 3/27/2009<br>carol : 8/10/2007<br>terry : 8/10/2007<br>joanna : 4/9/2003<br>carol : 4/11/2001<br>mcapotos : 4/6/2001<br>carol : 4/5/2001<br>carol : 4/5/2001<br>carol : 4/4/2001<br>carol : 4/4/2001
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
</div>
</div>
</div>
<div class="visible-print-block mim-footer" style="position: relative;">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
<br />
Printed: March 5, 2025
</div>
</div>
</div>
</div>
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
<div class="modal-dialog" role="document">
<div class="modal-content">
<div class="modal-header">
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">&times;</span></button>
<h4 class="modal-title" id="mimDonationPopupModalTitle">
OMIM Donation:
</h4>
</div>
<div class="modal-body">
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Dear OMIM User,
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
To ensure long-term funding for the OMIM project, we have diversified
our revenue stream. We are determined to keep this website freely
accessible. Unfortunately, it is not free to produce. Expert curators
review the literature and organize it to facilitate your work. Over 90%
of the OMIM's operating expenses go to salary support for MD and PhD
science writers and biocurators. Please join your colleagues by making a
donation now and again in the future. Donations are an important
component of our efforts to ensure long-term funding to provide you the
information that you need at your fingertips.
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Thank you in advance for your generous support, <br />
Ada Hamosh, MD, MPH <br />
Scientific Director, OMIM <br />
</p>
</div>
</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
Reference in a new issue View git blame Copy permalink