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/248600

5441 lines
480 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
- #248600 - MAPLE SYRUP URINE DISEASE, TYPE IA; MSUD1A
- 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=248600"><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">#248600</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/248600"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="/phenotypicSeries/PS248600"> <strong>Phenotypic Series</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="#clinicalManagement">Clinical Management</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#heterogeneity">Heterogeneity</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</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="#populationGenetics">Population Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</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=MAPLE SYRUP URINE DISEASE, TYPE IA" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</div>
<div id="mimEuroGentestFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20168&Typ=Pat" title="Classic maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Classic maple syrup urine …&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20169&Typ=Pat" title="Intermediate maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Intermediate maple syrup u…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20170&Typ=Pat" title="Intermittent maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Intermittent maple syrup u…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20171&Typ=Pat" title="Thiamine-responsive maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Thiamine-responsive maple …&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=708&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Maple syrup urine disease&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1319/" 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/4453" 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=248600[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="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Newborn Screening</div>
<div id="mimNewbornScreeningFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Leucine.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Leucine-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
</div>
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268145" title="Classic maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Classic maple syrup urine …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268162" title="Intermediate maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Intermediate maple syrup u…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268173" title="Intermittent maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Intermittent maple syrup u…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268184" title="Thiamine-responsive maple syrup urine disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Thiamine-responsive maple …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=511" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Maple syrup urine disease</a></div>
</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:9269" 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/248600" 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/OMIA000627/" 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:9269" 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:248600" 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>ORPHA:</strong> 268145, 268162, 268173, 268184, 511<br />
<strong>DO:</strong> 9269<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>
248600
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MAPLE SYRUP URINE DISEASE, TYPE IA; MSUD1A
</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">
MAPLE SYRUP URINE DISEASE; MSUD<br />
BRANCHED-CHAIN KETOACIDURIA<br />
BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY<br />
BCKD DEFICIENCY<br />
KETO ACID DECARBOXYLASE DEFICIENCY
</span>
</h4>
</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/19/730?start=-3&limit=10&highlight=730">
19q13.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Maple syrup urine disease, type Ia
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248600"> 248600 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
BCKDHA
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608348"> 608348 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/248600" 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">
<a href="/phenotypicSeries/PS248600" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', '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/248600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/248600" 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">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</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> Pancreas </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pancreatitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75694006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75694006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K85.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K85.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030305&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030305</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001733</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001733</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Feeding problems <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274540003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a>, <a href="https://bioportal.bioontology.org/search?q=C0699815&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0699815</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br /> -
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> 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">
- Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
Coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/371632003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">371632003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405809000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405809000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0543874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0543874</a>, <a href="https://bioportal.bioontology.org/search?q=C3146279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3146279</a>, <a href="https://bioportal.bioontology.org/search?q=C0009421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span><br /> -
Mental retardation if untreated <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856609&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856609</a>]</span><br /> -
Hypertonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56731001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56731001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41581000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41581000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026826&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026826</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001276</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001276</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 /> -
Cerebral edema <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2032001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2032001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span><br /> -
Hallucinations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7011001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7011001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R44.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R44.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018524</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000738</a>]</span><br /> -
Brain MRI shows diffusion abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550524</a>]</span><br /> -
White matter signal abnormalities in various brain regions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550525</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Life-threatening metabolic decompensation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1968665&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1968665</a>]</span><br /> -
Ketosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56051008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56051008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2538008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2538008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220982&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220982</a>, <a href="https://bioportal.bioontology.org/search?q=C0022638&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022638</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001946" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001946</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001993</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001946" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001946</a>]</span><br /> -
Hypoglycemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237630007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237630007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271327008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271327008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302866003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302866003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1179458001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1179458001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E16.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E16.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/251.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">251.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020615</a>, <a href="https://bioportal.bioontology.org/search?q=C5767385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5767385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span><br /> -
Lactic acidosis in E3-deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855387&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855387</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">
- Elevated plasma branched chain amino acids (leucine, isoleucine, valine) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855374</a>]</span><br /> -
Maple syrup urine odor <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241584</a>]</span><br /> -
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855375&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855375</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27718001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27718001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E71.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E71.0</a>]</span><br /> -
Elevated plasma alloisoleucine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855376</a>]</span><br /> -
Positive urine DNPH screening test <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855377</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">
- Five clinical variants of MSUD unassociated with genotype<br /> -
(1) Classic severe (onset of symptoms 4 to 7 days of age) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255333006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255333006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255301002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255301002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0439858&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0439858</a>, <a href="https://bioportal.bioontology.org/search?q=C0439658&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0439658</a>]</span><br /> -
(2) Intermittent <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7087005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7087005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0205267&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0205267</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031796" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031796</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031796" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031796</a>]</span><br /> -
(3) Intermediate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11896004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11896004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5202835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5202835</a>, <a href="https://bioportal.bioontology.org/search?q=C0205103&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0205103</a>, <a href="https://bioportal.bioontology.org/search?q=C1550465&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1550465</a>, <a href="https://bioportal.bioontology.org/search?q=C4722218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4722218</a>]</span><br /> -
(4) Thiamine-responsive form<br /> -
(5) Dihydrolipoyl dehydrogenase (E3)-deficient<br /> -
Worldwide incidence of 1 in 185,000 live births<br /> -
In inbred Old Order Mennonite population of Lancaster County, MSUD prevalence is 1/176 newborns<br /> -
Death in untreated children<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 branched chain keto acid dehydrogenase E1, alpha polypeptide gene (BCKDHA, <a href="/entry/608348#0001">608348.0001</a>)<br /> -
Caused by mutation in the branched chain keto acid dehydrogenase E1, beta polypeptide gene (BCKDHB, <a href="/entry/248611#0001">248611.0001</a>)<br /> -
Caused by mutation in the dihydrolipoamide branched chain transacylase gene (DBT, <a href="/entry/248610#0001">248610.0001</a>)<br /> -
Caused by mutation in the dihydrolipoamide dehydrogenase gene (DLD, <a href="/entry/238331#0001">238331.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Maple syrup urine disease
- <a href="/phenotypicSeries/PS248600">PS248600</a>
- 5 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/836?start=-3&limit=10&highlight=836"> 1p21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620699"> Maple syrup urine disease, type II </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/620699"> 620699 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248610"> DBT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248610"> 248610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/400?start=-3&limit=10&highlight=400"> 4q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615135"> Maple syrup urine disease, mild variant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/615135"> 615135 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611065"> PPM1K </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611065"> 611065 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/669?start=-3&limit=10&highlight=669"> 6q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620698"> Maple syrup urine disease, type Ib </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/620698"> 620698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248611"> BCKDHB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248611"> 248611 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/583?start=-3&limit=10&highlight=583"> 7q31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/246900"> Dihydrolipoamide dehydrogenase deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/246900"> 246900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/238331"> DLD </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/238331"> 238331 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/730?start=-3&limit=10&highlight=730"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248600"> Maple syrup urine disease, type Ia </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/248600"> 248600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608348"> BCKDHA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608348"> 608348 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" 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 maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (<a href="/entry/608348">608348</a>), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine.</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 major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; <a href="/entry/246900">246900</a>). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (<a href="#9" class="mim-tip-reference" title="Chuang, D. T., Shih, V. E. &lt;strong&gt;Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005."None>Chuang and Shih, 2001</a>).</p><p>The classic form, which comprises 75% of MSUD patients, is manifested within the first 2 weeks of life with poor feeding, lethargy, seizures, coma, and death if untreated. Intermediate MSUD is associated with elevated BCAAs and BCKA, with progressive mental retardation and developmental delay without a history of catastrophic illness. The diagnosis is usually delayed for many months. An intermittent form of MSUD may have normal levels of BCAAs, normal intelligence and development until a stress, e.g., infection, precipitates decompensation with ketoacidosis and neurologic symptoms, which are usually reversed with dietary treatment. Thiamine-responsive MSUD is similar to the intermediate phenotype but responds to pharmacologic doses of thiamine with normalization of BCAAs. The E3-deficient MSUD is caused by defects in the dehydrogenase (E3) component of the BCKAD complex that is common to the pyruvate and alpha-ketoglutarate dehydrogenase complexes. Patients with E3 deficiency have dysfunction of all 3 enzyme complexes, and patients usually die in infancy with severe lactic acidosis (summary by <a href="#10" class="mim-tip-reference" title="Chuang, J. L., Davie, J. R., Chinsky, J. M., Wynn, R. M., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular and biochemical basis of intermediate maple syrup urine disease: occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of Hispanic-Mexican patients.&lt;/strong&gt; J. Clin. Invest. 95: 954-963, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7883996/&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;7883996&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI117804&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="7883996">Chuang et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7883996" 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>Genetic Heterogeneity of Maple Syrup Urine Disease</em></strong></p><p>
MSUD1B (<a href="/entry/620698">620698</a>) is caused by mutation in the BCKDHB gene (<a href="/entry/248611">248611</a>) on chromosome 6q14, and MSUD2 (<a href="/entry/620699">620699</a>) is caused by mutation in the DBT gene (<a href="/entry/248610">248610</a>) on chromosome 1p21.</p><p>Mutation in the E3 component of the BCKDC complex, DLD (<a href="/entry/238331">238331</a>), on chromosome 7q31, causes an overlapping but more severe phenotype known as dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>). DLDD is sometimes referred to as MSUD3.</p><p>See also a mild variant of MSUD (MSUDMV; <a href="/entry/615135">615135</a>), caused by mutation in the regulatory gene PPM1K (<a href="/entry/611065">611065</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><strong><em>Early Reports of Classic MSUD</em></strong></p><p>
In classic MSUD, which is the most common form of the disorder, 50% or more of the keto acids are derived from leucine, and the activity of the BCKD complex is less than 2% of normal. Affected newborns appear normal at birth, with symptoms developing between 4 and 7 days of age. The infants show lethargy, weight loss, metabolic derangement, and progressive neurologic signs of altering hypotonia and hypertonia, reflecting a severe encephalopathy. Seizures and coma usually occur, followed by death if untreated (<a href="#9" class="mim-tip-reference" title="Chuang, D. T., Shih, V. E. &lt;strong&gt;Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005."None>Chuang and Shih, 2001</a>).</p><p><a href="#42" class="mim-tip-reference" title="Menkes, J. H., Hurst, P. L., Craig, J. M. &lt;strong&gt;A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance.&lt;/strong&gt; Pediatrics 14: 462-467, 1954.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13214961/&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;13214961&lt;/a&gt;]" pmid="13214961">Menkes et al. (1954)</a> reported a familial syndrome in which 4 sibs had progressive infantile cerebral dysfunction associated with an unusual urinary substance. Onset was in the first week of life, with death by 3 months of age. The urine had an odor resembling maple syrup. Referring to the syndrome as 'maple syrup urine disease,' <a href="#69" class="mim-tip-reference" title="Westall, R. G., Dancis, J., Miller, S. &lt;strong&gt;Maple syrup urine disease.&lt;/strong&gt; Am. J. Dis. Child. 94: 571-572, 1957."None>Westall et al. (1957)</a> found that the levels of branched-chain amino acids, leucine, isoleucine, and valine, were greatly elevated. <a href="#43" class="mim-tip-reference" title="Menkes, J. H. &lt;strong&gt;Maple syrup urine disease: isolation and identification of organic acids in the urine.&lt;/strong&gt; Pediatrics 23: 348-353, 1959.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13633350/&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;13633350&lt;/a&gt;]" pmid="13633350">Menkes (1959)</a> isolated and identified the corresponding keto acids in the urine of affected patients, suggesting that the catabolic pathways of the branched-chain amino acids were blocked at the decarboxylation step. <a href="#14" class="mim-tip-reference" title="Dancis, J., Levitz, M., Westall, R. G. &lt;strong&gt;Maple syrup urine disease: branched-chain ketoaciduria.&lt;/strong&gt; Pediatrics 25: 72-79, 1960.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13813934/&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;13813934&lt;/a&gt;]" pmid="13813934">Dancis et al. (1960)</a> also referred to the disorder as 'branched-chain ketoaciduria.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13214961+13633350+13813934" 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="#70" class="mim-tip-reference" title="Wong, P. W. K., Justice, P., Smith, G. F., Hsia, D. Y.-Y. &lt;strong&gt;A case of classical maple syrup urine disease, &#x27;thiamine non-responsive&#x27;.&lt;/strong&gt; Clin. Genet. 3: 27-33, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5066975/&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;5066975&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1972.tb01722.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="5066975">Wong et al. (1972)</a> reported a case of classic MSUD. <a href="#17" class="mim-tip-reference" title="DiGeorge, A. M., Rezvani, I., Garibaldi, L. R., Schwartz, M. &lt;strong&gt;Prospective study of maple-syrup-urine disease for the first four days of life.&lt;/strong&gt; New Eng. J. Med. 307: 1492-1495, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7144815/&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;7144815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198212093072405&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="7144815">DiGeorge et al. (1982)</a> made important observations on the course of classic MSUD in the first 4 days of life when an affected child was on a diet devoid of branched-chain amino acids. Although the branched-chain amino acids were normal in cord blood, serum leucine was significantly elevated by 4 to 14 hours of age and rose progressively thereafter, permitting an accurate and early diagnosis. However, <a href="#62" class="mim-tip-reference" title="Shih, V. E. &lt;strong&gt;Maple-syrup-urine disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 310: 596-597, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6694715/&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;6694715&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/nejm198403013100916&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="6694715">Shih (1984)</a> emphasized that classic MSUD may be missed in newborn screening because of slow rise of blood leucine levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7144815+5066975+6694715" 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="#25" class="mim-tip-reference" title="Frezal, J., Amedee-Manesme, O., Mitchell, G., Heuertz, S., Rey, F., Rey, J., Saudubray, J. M. &lt;strong&gt;Maple syrup urine disease: two different forms within a single family.&lt;/strong&gt; Hum. Genet. 71: 89-91, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4029957/&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;4029957&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00295676&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="4029957">Frezal et al. (1985)</a> observed a family in which 2 different forms of MSUD occurred. The proposita had an acute neonatal form; 2 of her sisters had an almost asymptomatic form which the authors thought represented compound heterozygosity for the classic mutant and a partial variant. The proband did not respond to thiamine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4029957" 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>Early Reports of Intermediate MSUD</em></strong></p><p>
<a href="#58" class="mim-tip-reference" title="Schulman, J. D., Lustberg, T. J., Kennedy, J. L., Museles, M., Seegmiller, J. E. &lt;strong&gt;A new variant of maple syrup urine disease (branched-chain ketoaciduria): clinical and biochemical evaluation.&lt;/strong&gt; Am. J. Med. 49: 118-124, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5431474/&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;5431474&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0002-9343(70)80121-8&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="5431474">Schulman et al. (1970)</a> first described intermediate MSUD in a 19-month-old patient who was being evaluated for mental retardation. She had normal physical growth but severe developmental delay. She had mild systemic acidosis and markedly increased levels of plasma branched-chain amino acids and urinary branched-chain keto acids. Protein restriction was effective, but thiamine administration was not. The patient had 15 to 25% residual BCKD activity in leukocytes and fibroblasts. <a href="#35" class="mim-tip-reference" title="Kalyanaraman, K., Chamukuttan, S., Arjundas, G., Gajanan, N., Ramamurthi, B. &lt;strong&gt;Maple syrup urine disease (branched-chain keto-aciduria): variant type manifesting as hyperkinetic behaviour and mental retardation--report of two cases.&lt;/strong&gt; J. Neurol. Sci. 15: 209-218, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5010106/&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;5010106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(72)90008-1&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="5010106">Kalyanaraman et al. (1972)</a> reported 2 patients with the intermediate form of MSUD manifesting as hyperkinetic behavior and mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5431474+5010106" 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="Chhabria, S., Tomasi, L. G., Wong, W. K. &lt;strong&gt;Ophthalmoplegia and bulbar palsy in a variant form of maple syrup urine disease.&lt;/strong&gt; Ann. Neurol. 6: 71-72, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/507761/&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;507761&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410060118&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="507761">Chhabria et al. (1979)</a> reported a neonate who presented with ophthalmoplegia and was later found to have intermediate MSUD with residual BCKD complex activity. They noted that 2 similar cases with MSUD and ophthalmoplegia had previously been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=507761" 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="#28" class="mim-tip-reference" title="Gonzalez-Rios, M. C., Chuang, D. T., Cox, R. P., Schmidt, K., Knopf, K., Packman, S. &lt;strong&gt;A distinct variant of intermediate maple syrup urine disease.&lt;/strong&gt; Clin. Genet. 27: 153-159, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3978850/&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;3978850&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1985.tb00203.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="3978850">Gonzalez-Rios et al. (1985)</a> reported a boy with intermediate MSUD who presented at age 10 months in ketoacidotic coma, with a history of irritability, poor feeding, and growth and developmental delay. Branched-chain amino acid restriction resulted in normal growth and development by age 42 months, but thiamine was not effective. The authors determined that the defect was in the catalytic activity of the E1 component of the BCKD complex, but there was some residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3978850" 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="#57" class="mim-tip-reference" title="Schadewaldt, P., Bodner-Leidecker, A., Hammen, H.-W., Wendel, U. &lt;strong&gt;Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease.&lt;/strong&gt; Pediat. Res. 49: 627-635, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11328944/&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;11328944&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-200105000-00004&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="11328944">Schadewaldt et al. (2001)</a> determined whole-body L-leucine oxidation in MSUD patients. In 4 patients with classic MSUD, L-leucine oxidation was too low to be measurable. In 2 females with a severe variant form of the disease, L-leucine oxidation was about 4% of control. In 6 milder variants, including intermediates, the estimates for residual whole-body L-leucine oxidation ranged from 19 to 86% (59 +/- 24%) of control, and were substantially higher than the residual branched-chain 2-oxo acid dehydrogenase complex activities in the patients' fibroblasts (10 to 25% of control). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328944" 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>Early Reports of Intermittent MSUD</em></strong></p><p>
<a href="#46" class="mim-tip-reference" title="Morris, M. D., Lewis, B. D., Doolan, P. D., Harper, H. A. &lt;strong&gt;Clinical and biochemical observations on an apparently nonfatal variant of branched-chain ketoaciduria (maple syrup urine disease).&lt;/strong&gt; Pediatrics 28: 918-923, 1961.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14476272/&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;14476272&lt;/a&gt;]" pmid="14476272">Morris et al. (1961)</a> reported a 24-month-old female with intermittent MSUD. She was asymptomatic until age 16 months when she had recurrent episodic ataxia, lethargy, semicoma, and elevated urinary branched-chain keto acids following otitis media. Similarly, her younger brother was normal until about age 10 months when he had an acute episode. Dietary protein restriction was effective (see also <a href="#45" class="mim-tip-reference" title="Morris, M. D., Fisher, D. A., Fiser, R. &lt;strong&gt;Late-onset branched-chain ketoaciduria: (maple syrup urine disease).&lt;/strong&gt; J. Lancet 86: 149-152, 1966.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5904649/&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;5904649&lt;/a&gt;]" pmid="5904649">Morris et al., 1966</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5904649+14476272" 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>In 2 sibs of each of 2 families, <a href="#13" class="mim-tip-reference" title="Dancis, J., Hutzler, J., Rokkones, T. &lt;strong&gt;Intermittent branched-chain ketonuria: variant of maple-syrup-urine disease.&lt;/strong&gt; New Eng. J. Med. 276: 84-89, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6015521/&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;6015521&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196701122760204&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="6015521">Dancis et al. (1967)</a> observed intermittent MSUD. The children suffered from a transient neurologic disorder associated with elevation of branched-chain amino acids and keto acids in the urine as well as a distinctive odor to the urine. One sib of each family died during an attack. Late onset of symptoms and clinical normality between attacks differentiated the condition from classic MSUD. In addition, the level of leukocyte BCKD complex activity seemed to be higher than in the classic form of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6015521" 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>Two Norwegian families with the intermittent form were described by <a href="#26" class="mim-tip-reference" title="Goedde, H. W., Langenbeck, U., Brackertz, D., Keller, W., Rokkones, T., Halvorsen, S., Kiil, R., Merton, B. &lt;strong&gt;Clinical and biochemical-genetic aspects of intermittent branched-chain ketoaciduria. Report of two Scandinavian families.&lt;/strong&gt; Acta Paediat. Scand. 59: 83-87, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5452306/&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;5452306&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1970.tb15519.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="5452306">Goedde et al. (1970)</a>. They noted that in the intermittent form, only 1 parent shows decreased enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5452306" 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="#68" class="mim-tip-reference" title="Van der Horst, J. L., Wadman, S. K. &lt;strong&gt;A variant form of branched-chain keto aciduria: case report.&lt;/strong&gt; Acta Paediat. Scand. 60: 594-599, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5125167/&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;5125167&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1971.tb06996.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="5125167">Van der Horst and Wadman (1971)</a> described an intermittent form with severe episodes of acidosis with mental retardation that was partially reversed on dietary therapy. Other cases of intermittent MSUD were reported by <a href="#37" class="mim-tip-reference" title="Kiil, R., Rokkones, T. &lt;strong&gt;Late manifesting variant of branched-chain ketoaciduria (maple syrup urine disease).&lt;/strong&gt; Acta Paediat. (Stockh.) 53: 356-364, 1964.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14184314/&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;14184314&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1964.tb07789.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="14184314">Kiil and Rokkones (1964)</a>, <a href="#66" class="mim-tip-reference" title="Valman, H. B., Patrick, H. B., Seakins, A. D., Platt, J. W., Gompertz, D. &lt;strong&gt;Family with intermittent maple syrup urine disease.&lt;/strong&gt; Arch. Dis. Child. 48: 225-228, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4693464/&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;4693464&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.48.3.225&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="4693464">Valman et al. (1973)</a>, and <a href="#33" class="mim-tip-reference" title="Indo, Y., Akaboshi, I., Nobukuni, Y., Endo, F., Matsuda, I. &lt;strong&gt;Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity.&lt;/strong&gt; Hum. Genet. 80: 6-10, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3417306/&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;3417306&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00451447&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="3417306">Indo et al. (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5125167+4693464+3417306+14184314" 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>Early Reports of Thiamine-responsive MSUD</em></strong></p><p>
<a href="#60" class="mim-tip-reference" title="Scriver, C. R., MacKenzie, S., Clow, C. L., Delvin, E. &lt;strong&gt;Thiamine-responsive maple-syrup-urine disease.&lt;/strong&gt; Lancet 297: 310-312, 1971. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4100151/&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;4100151&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(71)91041-5&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="4100151">Scriver et al. (1971)</a> described a variant of MSUD in which the hyperaminoacidemia was completely corrected by thiamine hydrochloride (10 mg per day) with dietary restriction (see also <a href="#59" class="mim-tip-reference" title="Scriver, C. R., Clow, C. L., George, H. &lt;strong&gt;So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient.&lt;/strong&gt; J. Pediat. 107: 763-765, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4056978/&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;4056978&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(85)80413-3&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="4056978">Scriver et al., 1985</a>). <a href="#18" class="mim-tip-reference" title="Duran, M., Tielens, A. G. M., Wadman, S. K., Stigter, J. C. M., Kleijer, W. J. &lt;strong&gt;Effects of thiamine in a patient with a variant form branched-chain ketoaciduria.&lt;/strong&gt; Acta Paediat. Scand. 67: 367-372, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/654914/&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;654914&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1978.tb16336.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="654914">Duran et al. (1978)</a> and <a href="#19" class="mim-tip-reference" title="Duran, M., Wadman, S. K. &lt;strong&gt;Thiamine-responsive inborn errors of metabolism.&lt;/strong&gt; J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3930844/&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;3930844&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01800663&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="3930844">Duran and Wadman (1985)</a> reported successful treatment of MSUD with thiamine administration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4056978+654914+4100151+3930844" 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="Chuang, D. T., Ku, L. S., Cox, R. P. &lt;strong&gt;Biochemical basis of thiamin-responsive maple syrup urine disease.&lt;/strong&gt; Trans. Assoc. Am. Phys. 95: 196-204, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7182976/&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;7182976&lt;/a&gt;]" pmid="7182976">Chuang et al. (1982)</a> found that BCKDH complex activity in thiamine-responsive MSUD is about 30 to 40% the normal rate. Further studies showed that the primary defect in thiamine-responsive MSUD is reduced affinity of the mutant BCKD for thiamine pyrophosphate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7182976" 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>In 2 cases of MSUD responsive to thiamine administration, <a href="#74" class="mim-tip-reference" title="Zhang, B., Wappner, R. S., Brandt, I. K., Harris, R. A., Crabb, D. W. &lt;strong&gt;Sequence of the E1-alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease.&lt;/strong&gt; Am. J. Hum. Genet. 46: 843-846, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2316528/&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;2316528&lt;/a&gt;]" pmid="2316528">Zhang et al. (1990)</a> found that the sequence of the gene for the E1-alpha subunit was normal. The result was considered consistent with any of the following possibilities: that the thiamine-binding site involves the E1-beta subunit, that the binding site is on E1-alpha, but a mutation elsewhere in the complex alters the affinity of the thiamine-binding site by an allosteric interaction, or that the clinical response to thiamine is due to stabilization of the enzyme that has a mutation in either the E1-beta or the E2 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2316528" 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>Fenugreek Tea</em></strong></p><p>
In a report from Tunisia, <a href="#44" class="mim-tip-reference" title="Monastiri, K., Limame, K., Kaabachi, N., Kharrat, H., Bousnina, S., Pousse, H., Radhouane, M., Gueddiche, M. N., Snoussi, N. &lt;strong&gt;Fenugreek odour in maple syrup urine disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 614-615, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9266407/&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;9266407&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005335915708&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="9266407">Monastiri et al. (1997)</a> noted that since maple syrup is largely unknown by Mediterranean populations, the odor of the urine in MSUD is more reminiscent of fenugreek (Trigonella foenum graecum L.) than of maple syrup. Fenugreek beans are traditionally used by Mediterranean populations as an infusion for sick persons (<a href="#4" class="mim-tip-reference" title="Boukef, K., Souissi, H. R., Balansard, G. &lt;strong&gt;Contribution a l&#x27; etude des plantes utilisees en medecine traditionnelle Tunisienne.&lt;/strong&gt; Plantes medicinales Phytotherapie 16: 260-279, 1982."None>Boukef et al., 1982</a>), and its fragrant smell is disagreeable and well known in that area. <a href="#44" class="mim-tip-reference" title="Monastiri, K., Limame, K., Kaabachi, N., Kharrat, H., Bousnina, S., Pousse, H., Radhouane, M., Gueddiche, M. N., Snoussi, N. &lt;strong&gt;Fenugreek odour in maple syrup urine disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 614-615, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9266407/&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;9266407&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005335915708&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="9266407">Monastiri et al. (1997)</a> suggested that physicians in Mediterranean countries should keep in mind that a fenugreek odor of urine with neurologic distress in newborn infants, without a history of fenugreek ingestion by the mother of the baby, should raise a suspicion of MSUD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266407" 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="#61" class="mim-tip-reference" title="Sewell, A. C., Mosandl, A., Bohles, H. &lt;strong&gt;False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. (Letter)&lt;/strong&gt; New Eng. J. Med. 341: 769 only, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10475807/&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;10475807&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199909023411020&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="10475807">Sewell et al. (1999)</a> described a case of 'pseudo-maple syrup urine disease' caused by drinking fenugreek tea. The 5-week-old Egyptian infant had a 10-minute episode of unconsciousness while drinking bottled tea. He recovered spontaneously, but the parents nevertheless sought medical attention. On examination, the child was found to exude an aroma similar to that of Maggi (a widely available flavoring), and a spontaneously voided urine sample had a similar aroma. The parents indicated that the child had been given herbal tea (Helba tea) to reduce flatulence and prevent fever. This tea contains seeds of fenugreek. Analysis of the infant's urine revealed the presence of sotolone, the compound responsible for the aroma in maple syrup urine disease (<a href="#54" class="mim-tip-reference" title="Podebrad, F., Heil, M., Reichert, S., Mosandl, A., Sewell, A. C., Bohles, H. &lt;strong&gt;4,5-Dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 22: 107-114, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10234605/&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;10234605&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005433516026&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="10234605">Podebrad et al., 1999</a>). Tea prepared from fenugreek seeds was found to contain sotolone. <a href="#2" class="mim-tip-reference" title="Bartley, G. B., Hilty, M. D., Andreson, B. D., Clairmont, A. C., Maschke, S. P. &lt;strong&gt;&#x27;Maple-syrup&#x27; urine odor due to fenugreek ingestion.&lt;/strong&gt; New Eng. J. Med. 305: 467 only, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7254294/&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;7254294&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198108203050823&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="7254294">Bartley et al. (1981)</a> had reported a similar case. Since herbal teas are popular as home remedies, particularly in Middle Eastern countries, physicians should use caution when they are presented with young infants from such countries, to avoid unnecessary and costly investigations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10475807+10234605+7254294" 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="#36" class="mim-tip-reference" title="Kaplan, P., Mazur, A., Field, M. &lt;strong&gt;Psychometric assessment in maple syrup urine disease: prospective, controlled pilot study. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A7 only, 1989."None>Kaplan et al. (1989)</a> described psychometric testing on 9 girls and 7 boys with MSUD. They concluded that prospective or early treatment significantly improves the intellectual outcome and that poor biochemical control may adversely affect performance.</p><p><a href="#67" class="mim-tip-reference" title="Van Calcar, S. C., Harding, C. O., Davidson, S. R., Barness, L. A., Wolff, J. A. &lt;strong&gt;Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia.&lt;/strong&gt; Am. J. Med. Genet. 44: 641-646, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1481826/&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;1481826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440523&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="1481826">Van Calcar et al. (1992)</a> described a 25-year-old woman with classic MSUD who was diagnosed at the age of 11 days and was successfully treated with dietary restrictions. She was followed closely during a pregnancy, with delivery of a healthy baby whose length and weight were at the 5th centile. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1481826" 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="#3" class="mim-tip-reference" title="Bodner-Leidecker, A., Wendel, U., Saudubray, J.-M., Schadewaldt, P. &lt;strong&gt;Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation.&lt;/strong&gt; J. Inherit. Metab. Dis. 23: 805-818, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11196106/&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;11196106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026708618507&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="11196106">Bodner-Leidecker et al. (2000)</a> reported a patient with classic MSUD who had orthotopic liver transplantation at age 7 years due to a terminal liver failure triggered by a hepatitis A infection. The patient was maintained on an unrestricted diet, and plasma concentrations of branched-chain L-amino and 2-oxo acids were stable, yet at moderately increased levels (2- to 3-fold of control). L-alloisoleucine concentrations, however, remained remarkably elevated (greater than 5-fold of control). In vivo catabolism showed normal rates of L-alloisoleucine and leucine elimination. <a href="#3" class="mim-tip-reference" title="Bodner-Leidecker, A., Wendel, U., Saudubray, J.-M., Schadewaldt, P. &lt;strong&gt;Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation.&lt;/strong&gt; J. Inherit. Metab. Dis. 23: 805-818, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11196106/&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;11196106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026708618507&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="11196106">Bodner-Leidecker et al. (2000)</a> suggested that the enhanced substrate supply from extrahepatic sources was responsible for the elevation of plasma concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196106" 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="#47" class="mim-tip-reference" title="Morton, D. H., Strauss, K. A., Robinson, D. L., Puffenberger, E. G., Kelley, R. I. &lt;strong&gt;Diagnosis and treatment of maple syrup disease: a study of 36 patients.&lt;/strong&gt; Pediatrics 109: 999-1008, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12042535/&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;12042535&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.109.6.999&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="12042535">Morton et al. (2002)</a> reported 35 Mennonite patients with MSUD and homozygosity for the Y393N mutation (<a href="/entry/608348#0001">608348.0001</a>) in the BCKDHA gene and 1 non-Mennonite patient who was compound heterozygous for the Y393N mutation and a splice-site mutation. Using amino acid analysis of plasma or whole blood collected on filter paper, they identified 18 affected neonates between 12 and 24 hours of age. None of the infants identified before 3 days of age and managed according to the protocol suggested by the authors became ill during the neonatal period. MSUD was diagnosed after age 3 days in 18 infants, all of whom had the characteristic maple syrup-like odor and neurologic deficits, including dystonic posturing, seizures, and cerebral edema. Follow-up of all 36 patients showed that the overall rate of hospitalization after the neonatal period was only 0.56 days per patient per year (25% of which was accounted for by 2 patients), and all showed uniformly good developmental outcomes. Four patients developed life-threatening cerebral edema as a consequence of infection and metabolism intoxication, but all recovered. <a href="#47" class="mim-tip-reference" title="Morton, D. H., Strauss, K. A., Robinson, D. L., Puffenberger, E. G., Kelley, R. I. &lt;strong&gt;Diagnosis and treatment of maple syrup disease: a study of 36 patients.&lt;/strong&gt; Pediatrics 109: 999-1008, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12042535/&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;12042535&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.109.6.999&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="12042535">Morton et al. (2002)</a> presented a detailed treatment protocol for MSUD that was designed to inhibit endogenous protein catabolism, sustain protein synthesis, prevent amino acid deficiencies, and maintain normal serum osmolarity. The authors emphasized the importance of diagnosis within the first days of life and concluded that classic MSUD can be properly managed to allow a benign neonatal course, normal growth and development, and low hospitalization rates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12042535" 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="heterogeneity" class="mim-anchor"></a>
<h4 href="#mimHeterogeneityFold" id="mimHeterogeneityToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHeterogeneityToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<div id="mimHeterogeneityFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><strong><em>Genetic Heterogeneity</em></strong></p><p>
<a href="#39" class="mim-tip-reference" title="Lyons, L. B., Cox, R. P., Dancis, J. &lt;strong&gt;Complementation analysis of maple syrup urine disease in heterokaryons derived from cultured human fibroblasts.&lt;/strong&gt; Nature 243: 533-535, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4355237/&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;4355237&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/243533a0&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="4355237">Lyons et al. (1973)</a> sought genetic heterogeneity in maple syrup urine disease by the study of heterokaryons derived from cultured fibroblasts of different patients. Fibroblasts from one patient consistently complemented those from other particular patients by increasing the level of BCKD. Correlation with clinical expression could not be made. <a href="#63" class="mim-tip-reference" title="Singh, S., Willers, I., Goedde, H. W. &lt;strong&gt;Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.&lt;/strong&gt; Clin. Genet. 11: 277-284, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/192504/&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;192504&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1977.tb01313.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="192504">Singh et al. (1977)</a> and <a href="#34" class="mim-tip-reference" title="Jinno, Y., Akaboshi, I., Matsuda, I. &lt;strong&gt;Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease.&lt;/strong&gt; Hum. Genet. 68: 54-56, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6500555/&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;6500555&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00293872&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="6500555">Jinno et al. (1984)</a> likewise did complementation analysis to answer the question of genetic heterogeneity. <a href="#34" class="mim-tip-reference" title="Jinno, Y., Akaboshi, I., Matsuda, I. &lt;strong&gt;Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease.&lt;/strong&gt; Hum. Genet. 68: 54-56, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6500555/&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;6500555&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00293872&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="6500555">Jinno et al. (1984)</a> demonstrated the usefulness of lymphoid cell lines in such studies and found 2 complementation groups. Unlike the earlier 2 studies, the 2 groups corresponded to clinical groups: 3 cell lines were from patients with the variant type and 2 were from patients with the classic type. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4355237+6500555+192504" 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="Indo, Y., Akaboshi, I., Nobukuni, Y., Endo, F., Matsuda, I. &lt;strong&gt;Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity.&lt;/strong&gt; Hum. Genet. 80: 6-10, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3417306/&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;3417306&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00451447&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="3417306">Indo et al. (1988)</a> found altered BCKDH complex enzyme activity and kinetics that appeared to correspond with MSUD phenotype: classic, intermediate, and intermittent types of MSUD demonstrated increasing levels of complex activity, and were associated with sigmoidal, near-sigmoidal, and hyperbolic kinetics, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3417306" 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>By Northern and Western blot analysis of the E1-alpha and E2 proteins in cell cultures from 7 unrelated MSUD patients, <a href="#22" class="mim-tip-reference" title="Fisher, C. W., Chuang, J. L., Griffin, T. A., Lau, K. S., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular phenotypes in cultured maple syrup urine disease cells: complete E(1)-alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex.&lt;/strong&gt; J. Biol. Chem. 264: 3448-3453, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2914958/&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;2914958&lt;/a&gt;]" pmid="2914958">Fisher et al. (1989)</a> demonstrated several distinct molecular phenotypes according to mRNA and protein-subunit contents, demonstrating the genetic complexity of MSUD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2914958" 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>The transmission pattern of MSUD1A in the family reported by Zhang et al. (<a href="#73" class="mim-tip-reference" title="Zhang, B., Edenberg, H. J., Crabb, D. W., Harris, R. A. &lt;strong&gt;Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.&lt;/strong&gt; J. Clin. Invest. 83: 1425-1429, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2703538/&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;2703538&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI114033&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="2703538">1989</a>, <a href="#75" class="mim-tip-reference" title="Zhang, B., Zhao, Y., Harris, R. A., Crabb, D. W. &lt;strong&gt;Molecular defects in the E1-alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.&lt;/strong&gt; Molec. Biol. Med. 8: 39-47, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1943689/&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;1943689&lt;/a&gt;]" pmid="1943689">1991</a>) and <a href="#11" class="mim-tip-reference" title="Chuang, J. L., Fisher, C. R., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular basis of maple syrup urine disease: novel mutations at the E1-alpha locus that impair E1(alpha-2-beta-2) assembly or decrease steady-state E1-alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.&lt;/strong&gt; Am. J. Hum. Genet. 55: 297-304, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8037208/&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;8037208&lt;/a&gt;]" pmid="8037208">Chuang et al. (1994)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1943689+2703538+8037208" 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>In a patient with classic MSUD, Zhang et al. (<a href="#73" class="mim-tip-reference" title="Zhang, B., Edenberg, H. J., Crabb, D. W., Harris, R. A. &lt;strong&gt;Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.&lt;/strong&gt; J. Clin. Invest. 83: 1425-1429, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2703538/&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;2703538&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI114033&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="2703538">1989</a>, <a href="#75" class="mim-tip-reference" title="Zhang, B., Zhao, Y., Harris, R. A., Crabb, D. W. &lt;strong&gt;Molecular defects in the E1-alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.&lt;/strong&gt; Molec. Biol. Med. 8: 39-47, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1943689/&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;1943689&lt;/a&gt;]" pmid="1943689">1991</a>) identified a mutation in the gene encoding the E1-alpha subunit (<a href="/entry/608348#0001">608348.0001</a>). <a href="#11" class="mim-tip-reference" title="Chuang, J. L., Fisher, C. R., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular basis of maple syrup urine disease: novel mutations at the E1-alpha locus that impair E1(alpha-2-beta-2) assembly or decrease steady-state E1-alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.&lt;/strong&gt; Am. J. Hum. Genet. 55: 297-304, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8037208/&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;8037208&lt;/a&gt;]" pmid="8037208">Chuang et al. (1994)</a> later identified a second mutation in the BCKDHA gene in this patient (<a href="/entry/608348#0002">608348.0002</a>). Each parent was heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1943689+2703538+8037208" 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>In 3 of 4 unrelated Hispanic-Mexican patients with intermediate MSUD, <a href="#10" class="mim-tip-reference" title="Chuang, J. L., Davie, J. R., Chinsky, J. M., Wynn, R. M., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular and biochemical basis of intermediate maple syrup urine disease: occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of Hispanic-Mexican patients.&lt;/strong&gt; J. Clin. Invest. 95: 954-963, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7883996/&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;7883996&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI117804&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="7883996">Chuang et al. (1995)</a> identified a homozygous mutation in the BCKDHA gene (<a href="/entry/608348#0003">608348.0003</a>). The fourth patient was homozygous for a different mutation in the BCKDHA gene (<a href="/entry/608348#0004">608348.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7883996" 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="#53" class="mim-tip-reference" title="Patel, M. S., Harris, R. A. &lt;strong&gt;Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.&lt;/strong&gt; FASEB J. 9: 1164-1172, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7672509/&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;7672509&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1096/fasebj.9.12.7672509&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="7672509">Patel and Harris (1995)</a> provided a schematic representation of 7 point mutations, 1 small deletion, and 1 small insertion reported in the BCKDHA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7672509" 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="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="#51" class="mim-tip-reference" title="Nellis, M. M., Kasinski, A., Carlson, M., Allen, R., Schaefer, A. M., Schwartz, E. M., Danner, D. J. &lt;strong&gt;Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression.&lt;/strong&gt; Molec. Genet. Metab. 80: 189-195, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14567968/&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;14567968&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s1096-7192(03)00144-6&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="14567968">Nellis et al. (2003)</a> evaluated and compared the clinical course of 11 unrelated patients with MSUD, including 3 with mutations in the E1-alpha gene, 5 with mutations in the E1-beta gene, and 3 with mutations in the E2 gene (2 were sibs). All had residual BCKD activity less than 3% of control values. All patients except 2, 1 with E1-alpha and 1 with an E1-beta mutations, had documented episodes of metabolic decompensation. IQ greater than 90 was observed in 70% of patients. Patients with mutations in the E1-alpha gene tended to have decreased IQs compared to other patients. In general, however, the results indicated no significant impact of 1 mutant locus to another in determining clinical outcome. The most important factor in determining outcome was early identification and institution of a protein-modified diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14567968" 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>Among 15 patients with variant forms of MSUD, <a href="#24" class="mim-tip-reference" title="Flaschker, N., Feyen, O., Fend, S., Simon, E., Schadewaldt, P., Wendel, U. &lt;strong&gt;Description of the mutations in 15 subjects with variant forms of maple syrup urine disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 30: 903-909, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17922217/&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;17922217&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-007-0579-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="17922217">Flaschker et al. (2007)</a> found that more severe phenotypes tended to be associated with mutations in the BCKDHA gene, whereas milder variants tended to be associated with mutations in the BCKDHB and DBT genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17922217" 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="populationGenetics" class="mim-anchor"></a>
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In a mobile, urban, predominantly white population of New England, <a href="#38" class="mim-tip-reference" title="Levy, H. L. &lt;strong&gt;To genetic screening.&lt;/strong&gt; Adv. Hum. Genet. 4: 389-394, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4783333/&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;4783333&lt;/a&gt;]" pmid="4783333">Levy (1973)</a> found a frequency of MSUD of 1 in 290,000 on newborn screening. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4783333" 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>The highest reported frequency of MSUD was observed among the Old Order Mennonites of Pennsylvania (<a href="#1" class="mim-tip-reference" title="Auerbach, V. H., DiGeorge, A. &lt;strong&gt;Maple syrup urine disease. In: Hommes, F. A.; Van den Berg, C. J. (eds.): Inborn Errors of Metabolism.&lt;/strong&gt; London: Academic Press (pub.) 1973. P. 337."None>Auerbach and DiGeorge, 1973</a>; <a href="#49" class="mim-tip-reference" title="Naylor, E. W. &lt;strong&gt;Newborn screening for maple syrup urine disease (branched chain ketoaciduria). In: Bickel, H.; Guthrie, R.; Hammersen, G. (eds.): Neonatal Screening for Inborn Errors of Metabolism.&lt;/strong&gt; Berlin: Springer-Verlag (pub.) 1980. P. 19."None>Naylor, 1980</a>; <a href="#40" class="mim-tip-reference" title="Marshall, L., DiGeorge, A. &lt;strong&gt;Maple syrup urine disease in the Old Order Mennonites. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 33: 139A only, 1981."None>Marshall and DiGeorge, 1981</a>). In conservative Mennonites of eastern Pennsylvania, classic MSUD has a frequency as high as 1 in 176 births (<a href="#17" class="mim-tip-reference" title="DiGeorge, A. M., Rezvani, I., Garibaldi, L. R., Schwartz, M. &lt;strong&gt;Prospective study of maple-syrup-urine disease for the first four days of life.&lt;/strong&gt; New Eng. J. Med. 307: 1492-1495, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7144815/&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;7144815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198212093072405&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="7144815">DiGeorge et al., 1982</a>). <a href="#41" class="mim-tip-reference" title="Matsuda, I., Nobukuni, Y., Mitsubuchi, H., Indo, Y., Endo, F., Asaka, J., Harada, A. &lt;strong&gt;A T-to-A substitution in the E1-alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite (sic) maple syrup urine disease patients.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 172: 646-651, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2241958/&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;2241958&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0006-291x(90)90723-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="2241958">Matsuda et al. (1990)</a> demonstrated the specific defect in the Mennonite cases (see <a href="/entry/608348#0001">608348.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7144815+2241958" 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="#9" class="mim-tip-reference" title="Chuang, D. T., Shih, V. E. &lt;strong&gt;Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005."None>Chuang and Shih (2001)</a> noted a worldwide incidence of MSUD of 1 in 185,000 live births.</p><p>Using complementation assays in cells from 63 individuals with clinically diagnosed MSUD, <a href="#50" class="mim-tip-reference" title="Nellis, M. M., Danner, D. J. &lt;strong&gt;Gene preference in maple syrup urine disease.&lt;/strong&gt; Am. J. Hum. Genet. 68: 232-237, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11112664/&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;11112664&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11112664[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/10.1086/316950&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="11112664">Nellis and Danner (2001)</a> found that 33% of the cases were caused by mutations in the E1-alpha gene, 38% by mutations in the E1-beta gene, and 19% by mutations in the E2 gene. Ten percent of the tested cell lines gave ambiguous results by showing no complementation or restoration of activity with 2 gene products. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11112664" 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>In 11 children with MSUD from a Gypsy community in southern Portugal, <a href="#56" class="mim-tip-reference" title="Quental, S., Macedo-Ribeiro, S., Matos, R., Vilarinho, L., Martins, E., Teles, E. L., Rodrigues, E., Diogo, L., Garcia, P., Eusebio, F., Gaspar, A., Sequeira, S., Furtado, F., Lanca, I., Amorim, A., Prata, M. J. &lt;strong&gt;Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community.&lt;/strong&gt; Molec. Genet. Metab. 94: 148-156, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18378174/&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;18378174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2008.02.008&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="18378174">Quental et al. (2008)</a> identified a homozygous 1-bp deletion (117delC; <a href="/entry/608348#0009">608348.0009</a>) in the BCKDHA gene. By haplotype analysis, <a href="#55" class="mim-tip-reference" title="Quental, S., Gusmao, A., Rodriguez-Pombo, P., Ugarte, M., Vilarinho, L., Amorim, A., Prata, M. J. &lt;strong&gt;Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene.&lt;/strong&gt; Ann. Hum. Genet. 73: 298-303, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19456321/&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;19456321&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-1809.2009.00518.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="19456321">Quental et al. (2009)</a> showed that the 117delC mutation is a founder mutation in Portuguese Gypsies with a carrier frequency estimated to be 1.4%. An unrelated Spanish patient with the deletion who was not of Gypsy origin did not share the haplotype, indicating that it occurred independently. The deletion occurs within a poly-C tract and may represent a mutation hotspot in the BCKDHA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18378174+19456321" 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="#21" class="mim-tip-reference" title="Feuchtbaum, L., Carter, J., Dowray, S., Currier, R. J., Lorey, F. &lt;strong&gt;Birth prevalence of disorders detectable through newborn screening by race/ethnicity.&lt;/strong&gt; Genet. Med. 14: 937-945, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22766612/&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;22766612&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2012.76&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="22766612">Feuchtbaum et al. (2012)</a> reported the birth rates of selected metabolic, endocrine, hemoglobin, and cystic fibrosis disorders for specific racial/ethnic groups in a total of 2,282,138 newborns born between 2005 and 2010 in California who were screened using a blood sample collected via heel stick. Screening of 21,973 individuals of Middle Eastern ancestry gave an estimated birth prevalence for maple syrup urine disease of approximately 14 per 100,000 births; of 61,120 individuals of Filipino ancestry, approximately 2 per 100,000 births; and of 1,183,044 Hispanic individuals, approximately 1 per 100,000 births. Results for other ethnic groups were less than 1 per 100,000 births. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22766612" 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="animalModel" class="mim-anchor"></a>
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In polled Hereford calves with maple syrup urine disease, <a href="#75" class="mim-tip-reference" title="Zhang, B., Zhao, Y., Harris, R. A., Crabb, D. W. &lt;strong&gt;Molecular defects in the E1-alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.&lt;/strong&gt; Molec. Biol. Med. 8: 39-47, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1943689/&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;1943689&lt;/a&gt;]" pmid="1943689">Zhang et al. (1991)</a> demonstrated a C-to-T substitution in the E1-alpha gene that introduced a stop codon into the leader peptide of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1943689" 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="#29" class="mim-tip-reference" title="Gortz, P., Koller, H., Schwahn, B., Wendel, U., Siebler, M. &lt;strong&gt;Disturbance of cultured rat neuronal network activity depends on concentration and ratio of leucine and alpha-ketoisocaproate: implication for acute encephalopathy of maple syrup urine disease.&lt;/strong&gt; Pediat. Res. 53: 320-324, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12538793/&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;12538793&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/01.PDR.0000047521.50656.16&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="12538793">Gortz et al. (2003)</a> found that spontaneous network activity in primary dissociated embryonic rat neurons was reversibly reduced or blocked by increased extracellular leucine or alpha-ketoisocaproate in a dose-dependent fashion. In contrast, resting potential, various membrane currents, and intracellular calcium were unaffected by the substances. <a href="#29" class="mim-tip-reference" title="Gortz, P., Koller, H., Schwahn, B., Wendel, U., Siebler, M. &lt;strong&gt;Disturbance of cultured rat neuronal network activity depends on concentration and ratio of leucine and alpha-ketoisocaproate: implication for acute encephalopathy of maple syrup urine disease.&lt;/strong&gt; Pediat. Res. 53: 320-324, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12538793/&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;12538793&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/01.PDR.0000047521.50656.16&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="12538793">Gortz et al. (2003)</a> concluded that an abnormality of release or imbalance of concentration of glutaminergic/GABAergic neurotransmitters causes the acute neuronal dysfunction in maple syrup urine disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12538793" 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>In a large N-ethyl-N-nitrosourea (ENU)-induced mouse mutagenesis program, <a href="#72" class="mim-tip-reference" title="Wu, J.-Y., Kao, H.-J., Li, S.-C., Stevens, R., Hillman, S., Millington, D., Chen, Y.-T. &lt;strong&gt;ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease.&lt;/strong&gt; J. Clin. Invest. 113: 434-440, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14755340/&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;14755340&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14755340[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/10.1172/JCI19574&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="14755340">Wu et al. (2004)</a> identified a phenotype characterized by striking elevation of serum branched-chain amino acids and a moderate increase in arginine. Clinically, the affected mice also showed failure to thrive, weakness, decreased spontaneous movement, and thin hair, features seen in humans with maple syrup urine disease. In the affected mice, <a href="#72" class="mim-tip-reference" title="Wu, J.-Y., Kao, H.-J., Li, S.-C., Stevens, R., Hillman, S., Millington, D., Chen, Y.-T. &lt;strong&gt;ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease.&lt;/strong&gt; J. Clin. Invest. 113: 434-440, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14755340/&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;14755340&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14755340[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/10.1172/JCI19574&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="14755340">Wu et al. (2004)</a> identified a homozygous T-to-C transition in the 5-prime splicing site consensus sequence of exon 2 and intron 2 of the Bcat2 gene (<a href="/entry/113530">113530</a>), resulting in deletion of exon 2. RT-PCR showed markedly reduced amounts of Bcat2 mRNA in muscle and liver compared to controls. The authors noted that exon 2 contains the mitochondrial targeting leader sequence. A diet low in branched-chain amino acids resulted in clinical improvement in the mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14755340" 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>
<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="#Chuang1982" class="mim-tip-reference" title="Chuang, D. T., Ku, L. S., Kerr, D. S., Cox, R. P. &lt;strong&gt;Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures.&lt;/strong&gt; Am. J. Hum. Genet. 34: 416-424, 1982.">Chuang et al. (1982)</a>; <a href="#Chuang1982" class="mim-tip-reference" title="Chuang, D. T., Ku, L. S., Kerr, D. S., Cox, R. P. &lt;strong&gt;Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures.&lt;/strong&gt; Am. J. Hum. Genet. 34: 416-424, 1982.">Chuang et al. (1982)</a>; <a href="#Dancis1963" class="mim-tip-reference" title="Dancis, J., Hutzler, J., Levitz, M. &lt;strong&gt;The diagnosis of maple syrup disease (branched chain ketoaciduria) by the in vitro study of the peripheral leukocyte.&lt;/strong&gt; Pediatrics 32: 234-238, 1963.">Dancis et al. (1963)</a>; <a href="#Danner1985" class="mim-tip-reference" title="Danner, D. J., Armstrong, N., Heffelfinger, S. C., Sewell, E. T., Priest, J. H., Elsas, L. J. &lt;strong&gt;Absence of branched chain acyl-transferase as a cause of maple syrup urine disease.&lt;/strong&gt; J. Clin. Invest. 75: 858-860, 1985.">Danner et al. (1985)</a>; <a href="#Danner1978" class="mim-tip-reference" title="Danner, D. J., Wheeler, F. B., Lemmon, S. K., Elsas, L. J., II. &lt;strong&gt;In vivo and in vitro response of human branched chain alpha-ketoacid thiamine pyrophosphate.&lt;/strong&gt; Pediat. Res. 12: 235-238, 1978.">Danner et al. (1978)</a>; <a href="#Fekete1989" class="mim-tip-reference" title="Fekete, G., Plattner, R., Crabb, D. W., Zhang, B., Harris, R. A., Heerema, N., Palmer, C. G. &lt;strong&gt;Localization of the human gene for the E1-alpha subunit of branched chain keto acid dehydrogenase (BCKDHA) to chromosome 19q13.1-q13.2.&lt;/strong&gt; Cytogenet. Cell Genet. 50: 236-237, 1989.">Fekete et al. (1989)</a>; <a href="#Fisher1991" class="mim-tip-reference" title="Fisher, C. W., Lau, K. S., Fisher, C. R., Wynn, R. M., Cox, R. P., Chuang, D. T. &lt;strong&gt;A 17-bp insertion and a phe215-to-cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 174: 804-809, 1991.">Fisher et al. (1991)</a>; <a href="#Goedde1968" class="mim-tip-reference" title="Goedde, H. W., Langenbeck, U., Brackertz, D. &lt;strong&gt;Detection of heterozygotes in maple syrup urine disease: role of lymphocyte count.&lt;/strong&gt; Humangenetik 6: 189-190, 1968.">Goedde et al. (1968)</a>; <a href="#Heffelfinger1983" class="mim-tip-reference" title="Heffelfinger, S. C., Sewell, E. T., Danner, D. J. &lt;strong&gt;Identification of specific subunits of highly purified bovine liver branched chain ketoacid dehydrogenase.&lt;/strong&gt; Biochemistry 22: 5519-5522, 1983.">Heffelfinger et al.
(1983)</a>; <a href="#Heffelfinger1984" class="mim-tip-reference" title="Heffelfinger, S. C., Sewell, E. T., Elsas, L. J., Danner, D. J. &lt;strong&gt;Direct physical evidence for stabilization of branched-chain alpha-ketoacid dehydrogenase by thiamin pyrophosphate.&lt;/strong&gt; Am. J. Hum. Genet. 36: 802-807, 1984.">Heffelfinger et al. (1984)</a>; <a href="#Hong1996" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. &lt;strong&gt;Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.&lt;/strong&gt; Hum. Molec. Genet. 5: 1925-1930, 1996.">Hong et al. (1996)</a>; <a href="#Naughten1982" class="mim-tip-reference" title="Naughten, E. R., Jenkins, J., Francis, D. E. M., Leonard, J. V. &lt;strong&gt;Outcome of maple syrup urine disease.&lt;/strong&gt; Arch. Dis. Child. 57: 918-921, 1982.">Naughten et
al. (1982)</a>; <a href="#Norton1962" class="mim-tip-reference" title="Norton, P. M., Roitman, E., Snyderman, S. E., Holt, L. E., Jr. &lt;strong&gt;A new finding in maple-syrup-urine disease.&lt;/strong&gt; Lancet 279: 26-27, 1962. Note: Originally Volume I.">Norton et al. (1962)</a>; <a href="#Snyderman1967" class="mim-tip-reference" title="Snyderman, S. E. &lt;strong&gt;The therapy of maple syrup urine disease.&lt;/strong&gt; Am. J. Dis. Child. 113: 68-73, 1967.">Snyderman (1967)</a>; <a href="#Tiu1988" class="mim-tip-reference" title="Tiu, A. B., Naujokas, M., Eisenstein, R., Francke, U., Barton, D. E., Hoganson, G. E. &lt;strong&gt;Cloning and chromosome mapping of a cDNA encoding the E1-alpha subunit of branched chain ketoacid dehydrogenase (BCKAD). (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 43: A17 only, 1988.">Tiu et al.
(1988)</a>; <a href="#Woody1965" class="mim-tip-reference" title="Woody, N. C., Harris, J. A. &lt;strong&gt;Family screening studies in maple syrup urine disease (branched-chain ketoaciduria).&lt;/strong&gt; J. Pediat. 66: 1042-1048, 1965.">Woody and Harris (1965)</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="Auerbach1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Auerbach, V. H., DiGeorge, A.
<strong>Maple syrup urine disease. In: Hommes, F. A.; Van den Berg, C. J. (eds.): Inborn Errors of Metabolism.</strong>
London: Academic Press (pub.) 1973. P. 337.
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Bartley1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bartley, G. B., Hilty, M. D., Andreson, B. D., Clairmont, A. C., Maschke, S. P.
<strong>'Maple-syrup' urine odor due to fenugreek ingestion.</strong>
New Eng. J. Med. 305: 467 only, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7254294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7254294</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7254294" 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/NEJM198108203050823" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Bodner-Leidecker2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bodner-Leidecker, A., Wendel, U., Saudubray, J.-M., Schadewaldt, P.
<strong>Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation.</strong>
J. Inherit. Metab. Dis. 23: 805-818, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11196106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11196106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196106" 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:1026708618507" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Boukef1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Boukef, K., Souissi, H. R., Balansard, G.
<strong>Contribution a l' etude des plantes utilisees en medecine traditionnelle Tunisienne.</strong>
Plantes medicinales Phytotherapie 16: 260-279, 1982.
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Chhabria1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chhabria, S., Tomasi, L. G., Wong, W. K.
<strong>Ophthalmoplegia and bulbar palsy in a variant form of maple syrup urine disease.</strong>
Ann. Neurol. 6: 71-72, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/507761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">507761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=507761" 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/ana.410060118" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Chuang1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Cox, R. P.
<strong>Biochemical basis of thiamin-responsive maple syrup urine disease.</strong>
Trans. Assoc. Am. Phys. 95: 196-204, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7182976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7182976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7182976" 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="7" class="mim-anchor"></a>
<a id="Chuang1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Cox, R. P.
<strong>Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate.</strong>
Proc. Nat. Acad. Sci. 79: 3300-3304, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6954481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6954481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6954481" 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.79.10.3300" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Chuang1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Kerr, D. S., Cox, R. P.
<strong>Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures.</strong>
Am. J. Hum. Genet. 34: 416-424, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7081220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7081220</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7081220" 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="Chuang2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, D. T., Shih, V. E.
<strong>Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005.
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Chuang1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, J. L., Davie, J. R., Chinsky, J. M., Wynn, R. M., Cox, R. P., Chuang, D. T.
<strong>Molecular and biochemical basis of intermediate maple syrup urine disease: occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of Hispanic-Mexican patients.</strong>
J. Clin. Invest. 95: 954-963, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7883996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7883996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7883996" 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/JCI117804" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Chuang1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, J. L., Fisher, C. R., Cox, R. P., Chuang, D. T.
<strong>Molecular basis of maple syrup urine disease: novel mutations at the E1-alpha locus that impair E1(alpha-2-beta-2) assembly or decrease steady-state E1-alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.</strong>
Am. J. Hum. Genet. 55: 297-304, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8037208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8037208</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8037208" 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="12" class="mim-anchor"></a>
<a id="Dancis1963" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dancis, J., Hutzler, J., Levitz, M.
<strong>The diagnosis of maple syrup disease (branched chain ketoaciduria) by the in vitro study of the peripheral leukocyte.</strong>
Pediatrics 32: 234-238, 1963.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14044451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14044451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14044451" 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="Dancis1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dancis, J., Hutzler, J., Rokkones, T.
<strong>Intermittent branched-chain ketonuria: variant of maple-syrup-urine disease.</strong>
New Eng. J. Med. 276: 84-89, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6015521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6015521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6015521" 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/NEJM196701122760204" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Dancis1960" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dancis, J., Levitz, M., Westall, R. G.
<strong>Maple syrup urine disease: branched-chain ketoaciduria.</strong>
Pediatrics 25: 72-79, 1960.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13813934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13813934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13813934" 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="15" class="mim-anchor"></a>
<a id="Danner1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danner, D. J., Armstrong, N., Heffelfinger, S. C., Sewell, E. T., Priest, J. H., Elsas, L. J.
<strong>Absence of branched chain acyl-transferase as a cause of maple syrup urine disease.</strong>
J. Clin. Invest. 75: 858-860, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3980729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3980729</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3980729" 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/JCI111783" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Danner1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danner, D. J., Wheeler, F. B., Lemmon, S. K., Elsas, L. J., II.
<strong>In vivo and in vitro response of human branched chain alpha-ketoacid thiamine pyrophosphate.</strong>
Pediat. Res. 12: 235-238, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/643394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">643394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=643394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-197803000-00016" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="DiGeorge1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
DiGeorge, A. M., Rezvani, I., Garibaldi, L. R., Schwartz, M.
<strong>Prospective study of maple-syrup-urine disease for the first four days of life.</strong>
New Eng. J. Med. 307: 1492-1495, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7144815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7144815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7144815" 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/NEJM198212093072405" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Duran1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Duran, M., Tielens, A. G. M., Wadman, S. K., Stigter, J. C. M., Kleijer, W. J.
<strong>Effects of thiamine in a patient with a variant form branched-chain ketoaciduria.</strong>
Acta Paediat. Scand. 67: 367-372, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/654914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">654914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=654914" 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.1651-2227.1978.tb16336.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Duran1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3930844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3930844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3930844" 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/BF01800663" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Fekete1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fekete, G., Plattner, R., Crabb, D. W., Zhang, B., Harris, R. A., Heerema, N., Palmer, C. G.
<strong>Localization of the human gene for the E1-alpha subunit of branched chain keto acid dehydrogenase (BCKDHA) to chromosome 19q13.1-q13.2.</strong>
Cytogenet. Cell Genet. 50: 236-237, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2805821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2805821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2805821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000132768" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Feuchtbaum2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Feuchtbaum, L., Carter, J., Dowray, S., Currier, R. J., Lorey, F.
<strong>Birth prevalence of disorders detectable through newborn screening by race/ethnicity.</strong>
Genet. Med. 14: 937-945, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22766612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22766612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22766612" 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/gim.2012.76" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Fisher1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fisher, C. W., Chuang, J. L., Griffin, T. A., Lau, K. S., Cox, R. P., Chuang, D. T.
<strong>Molecular phenotypes in cultured maple syrup urine disease cells: complete E(1)-alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex.</strong>
J. Biol. Chem. 264: 3448-3453, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2914958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2914958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2914958" 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="23" class="mim-anchor"></a>
<a id="Fisher1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fisher, C. W., Lau, K. S., Fisher, C. R., Wynn, R. M., Cox, R. P., Chuang, D. T.
<strong>A 17-bp insertion and a phe215-to-cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34.</strong>
Biochem. Biophys. Res. Commun. 174: 804-809, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0006-291x(91)91489-y" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Flaschker2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Flaschker, N., Feyen, O., Fend, S., Simon, E., Schadewaldt, P., Wendel, U.
<strong>Description of the mutations in 15 subjects with variant forms of maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 30: 903-909, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17922217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17922217</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17922217" 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/s10545-007-0579-x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Frezal1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Frezal, J., Amedee-Manesme, O., Mitchell, G., Heuertz, S., Rey, F., Rey, J., Saudubray, J. M.
<strong>Maple syrup urine disease: two different forms within a single family.</strong>
Hum. Genet. 71: 89-91, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4029957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4029957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4029957" 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/BF00295676" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Goedde1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goedde, H. W., Langenbeck, U., Brackertz, D., Keller, W., Rokkones, T., Halvorsen, S., Kiil, R., Merton, B.
<strong>Clinical and biochemical-genetic aspects of intermittent branched-chain ketoaciduria. Report of two Scandinavian families.</strong>
Acta Paediat. Scand. 59: 83-87, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5452306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5452306</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5452306" 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.1651-2227.1970.tb15519.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Goedde1968" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goedde, H. W., Langenbeck, U., Brackertz, D.
<strong>Detection of heterozygotes in maple syrup urine disease: role of lymphocyte count.</strong>
Humangenetik 6: 189-190, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5704438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5704438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5704438" 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/BF00297728" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Gonzalez-Rios1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gonzalez-Rios, M. C., Chuang, D. T., Cox, R. P., Schmidt, K., Knopf, K., Packman, S.
<strong>A distinct variant of intermediate maple syrup urine disease.</strong>
Clin. Genet. 27: 153-159, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3978850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3978850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3978850" 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.1399-0004.1985.tb00203.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Gortz2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gortz, P., Koller, H., Schwahn, B., Wendel, U., Siebler, M.
<strong>Disturbance of cultured rat neuronal network activity depends on concentration and ratio of leucine and alpha-ketoisocaproate: implication for acute encephalopathy of maple syrup urine disease.</strong>
Pediat. Res. 53: 320-324, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12538793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12538793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12538793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/01.PDR.0000047521.50656.16" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Heffelfinger1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Heffelfinger, S. C., Sewell, E. T., Danner, D. J.
<strong>Identification of specific subunits of highly purified bovine liver branched chain ketoacid dehydrogenase.</strong>
Biochemistry 22: 5519-5522, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6652074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6652074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6652074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1021/bi00293a011" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Heffelfinger1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Heffelfinger, S. C., Sewell, E. T., Elsas, L. J., Danner, D. J.
<strong>Direct physical evidence for stabilization of branched-chain alpha-ketoacid dehydrogenase by thiamin pyrophosphate.</strong>
Am. J. Hum. Genet. 36: 802-807, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6475955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6475955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6475955" 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="32" class="mim-anchor"></a>
<a id="Hong1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
Hum. Molec. Genet. 5: 1925-1930, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968745" 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/5.12.1925" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Indo1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Indo, Y., Akaboshi, I., Nobukuni, Y., Endo, F., Matsuda, I.
<strong>Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity.</strong>
Hum. Genet. 80: 6-10, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3417306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3417306</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3417306" 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/BF00451447" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Jinno1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jinno, Y., Akaboshi, I., Matsuda, I.
<strong>Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease.</strong>
Hum. Genet. 68: 54-56, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6500555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6500555</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6500555" 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/BF00293872" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Kalyanaraman1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kalyanaraman, K., Chamukuttan, S., Arjundas, G., Gajanan, N., Ramamurthi, B.
<strong>Maple syrup urine disease (branched-chain keto-aciduria): variant type manifesting as hyperkinetic behaviour and mental retardation--report of two cases.</strong>
J. Neurol. Sci. 15: 209-218, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5010106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5010106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5010106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(72)90008-1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Kaplan1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kaplan, P., Mazur, A., Field, M.
<strong>Psychometric assessment in maple syrup urine disease: prospective, controlled pilot study. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A7 only, 1989.
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Kiil1964" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kiil, R., Rokkones, T.
<strong>Late manifesting variant of branched-chain ketoaciduria (maple syrup urine disease).</strong>
Acta Paediat. (Stockh.) 53: 356-364, 1964.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14184314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14184314</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14184314" 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.1651-2227.1964.tb07789.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Levy1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Levy, H. L.
<strong>To genetic screening.</strong>
Adv. Hum. Genet. 4: 389-394, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4783333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4783333</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4783333" 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="39" class="mim-anchor"></a>
<a id="Lyons1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lyons, L. B., Cox, R. P., Dancis, J.
<strong>Complementation analysis of maple syrup urine disease in heterokaryons derived from cultured human fibroblasts.</strong>
Nature 243: 533-535, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4355237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4355237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4355237" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/243533a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Marshall1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Marshall, L., DiGeorge, A.
<strong>Maple syrup urine disease in the Old Order Mennonites. (Abstract)</strong>
Am. J. Hum. Genet. 33: 139A only, 1981.
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Matsuda1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matsuda, I., Nobukuni, Y., Mitsubuchi, H., Indo, Y., Endo, F., Asaka, J., Harada, A.
<strong>A T-to-A substitution in the E1-alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite (sic) maple syrup urine disease patients.</strong>
Biochem. Biophys. Res. Commun. 172: 646-651, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2241958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2241958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2241958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0006-291x(90)90723-z" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Menkes1954" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Menkes, J. H., Hurst, P. L., Craig, J. M.
<strong>A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance.</strong>
Pediatrics 14: 462-467, 1954.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13214961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13214961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13214961" 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="Menkes1959" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Menkes, J. H.
<strong>Maple syrup urine disease: isolation and identification of organic acids in the urine.</strong>
Pediatrics 23: 348-353, 1959.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13633350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13633350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13633350" 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="44" class="mim-anchor"></a>
<a id="Monastiri1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Monastiri, K., Limame, K., Kaabachi, N., Kharrat, H., Bousnina, S., Pousse, H., Radhouane, M., Gueddiche, M. N., Snoussi, N.
<strong>Fenugreek odour in maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 20: 614-615, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266407</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266407" 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:1005335915708" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Morris1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morris, M. D., Fisher, D. A., Fiser, R.
<strong>Late-onset branched-chain ketoaciduria: (maple syrup urine disease).</strong>
J. Lancet 86: 149-152, 1966.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5904649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5904649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5904649" 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="46" class="mim-anchor"></a>
<a id="Morris1961" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morris, M. D., Lewis, B. D., Doolan, P. D., Harper, H. A.
<strong>Clinical and biochemical observations on an apparently nonfatal variant of branched-chain ketoaciduria (maple syrup urine disease).</strong>
Pediatrics 28: 918-923, 1961.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14476272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14476272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14476272" 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="47" class="mim-anchor"></a>
<a id="Morton2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morton, D. H., Strauss, K. A., Robinson, D. L., Puffenberger, E. G., Kelley, R. I.
<strong>Diagnosis and treatment of maple syrup disease: a study of 36 patients.</strong>
Pediatrics 109: 999-1008, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12042535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12042535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12042535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1542/peds.109.6.999" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Naughten1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naughten, E. R., Jenkins, J., Francis, D. E. M., Leonard, J. V.
<strong>Outcome of maple syrup urine disease.</strong>
Arch. Dis. Child. 57: 918-921, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7181520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7181520</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7181520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.57.12.918" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Naylor1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naylor, E. W.
<strong>Newborn screening for maple syrup urine disease (branched chain ketoaciduria). In: Bickel, H.; Guthrie, R.; Hammersen, G. (eds.): Neonatal Screening for Inborn Errors of Metabolism.</strong>
Berlin: Springer-Verlag (pub.) 1980. P. 19.
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Nellis2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nellis, M. M., Danner, D. J.
<strong>Gene preference in maple syrup urine disease.</strong>
Am. J. Hum. Genet. 68: 232-237, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11112664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11112664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11112664[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=11112664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/316950" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Nellis2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nellis, M. M., Kasinski, A., Carlson, M., Allen, R., Schaefer, A. M., Schwartz, E. M., Danner, D. J.
<strong>Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression.</strong>
Molec. Genet. Metab. 80: 189-195, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14567968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14567968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14567968" 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/s1096-7192(03)00144-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Norton1962" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Norton, P. M., Roitman, E., Snyderman, S. E., Holt, L. E., Jr.
<strong>A new finding in maple-syrup-urine disease.</strong>
Lancet 279: 26-27, 1962. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14480431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14480431</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14480431" 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(62)92646-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Patel1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Patel, M. S., Harris, R. A.
<strong>Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.</strong>
FASEB J. 9: 1164-1172, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7672509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7672509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7672509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1096/fasebj.9.12.7672509" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Podebrad1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Podebrad, F., Heil, M., Reichert, S., Mosandl, A., Sewell, A. C., Bohles, H.
<strong>4,5-Dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 22: 107-114, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10234605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10234605</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10234605" 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:1005433516026" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Quental2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Quental, S., Gusmao, A., Rodriguez-Pombo, P., Ugarte, M., Vilarinho, L., Amorim, A., Prata, M. J.
<strong>Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene.</strong>
Ann. Hum. Genet. 73: 298-303, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19456321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19456321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19456321" 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.1469-1809.2009.00518.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Quental2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Quental, S., Macedo-Ribeiro, S., Matos, R., Vilarinho, L., Martins, E., Teles, E. L., Rodrigues, E., Diogo, L., Garcia, P., Eusebio, F., Gaspar, A., Sequeira, S., Furtado, F., Lanca, I., Amorim, A., Prata, M. J.
<strong>Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community.</strong>
Molec. Genet. Metab. 94: 148-156, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18378174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18378174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18378174" 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.2008.02.008" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="Schadewaldt2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schadewaldt, P., Bodner-Leidecker, A., Hammen, H.-W., Wendel, U.
<strong>Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease.</strong>
Pediat. Res. 49: 627-635, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328944</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-200105000-00004" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" class="mim-anchor"></a>
<a id="Schulman1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schulman, J. D., Lustberg, T. J., Kennedy, J. L., Museles, M., Seegmiller, J. E.
<strong>A new variant of maple syrup urine disease (branched-chain ketoaciduria): clinical and biochemical evaluation.</strong>
Am. J. Med. 49: 118-124, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5431474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5431474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5431474" 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/s0002-9343(70)80121-8" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Scriver1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scriver, C. R., Clow, C. L., George, H.
<strong>So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient.</strong>
J. Pediat. 107: 763-765, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4056978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4056978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4056978" 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/s0022-3476(85)80413-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="60" class="mim-anchor"></a>
<a id="Scriver1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scriver, C. R., MacKenzie, S., Clow, C. L., Delvin, E.
<strong>Thiamine-responsive maple-syrup-urine disease.</strong>
Lancet 297: 310-312, 1971. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4100151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4100151</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4100151" 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(71)91041-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="61" class="mim-anchor"></a>
<a id="Sewell1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sewell, A. C., Mosandl, A., Bohles, H.
<strong>False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. (Letter)</strong>
New Eng. J. Med. 341: 769 only, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10475807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10475807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10475807" 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/NEJM199909023411020" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="62" class="mim-anchor"></a>
<a id="Shih1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shih, V. E.
<strong>Maple-syrup-urine disease. (Letter)</strong>
New Eng. J. Med. 310: 596-597, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6694715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6694715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6694715" 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/nejm198403013100916" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="63" class="mim-anchor"></a>
<a id="Singh1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Singh, S., Willers, I., Goedde, H. W.
<strong>Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.</strong>
Clin. Genet. 11: 277-284, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/192504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">192504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=192504" 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.1399-0004.1977.tb01313.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="64" class="mim-anchor"></a>
<a id="Snyderman1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Snyderman, S. E.
<strong>The therapy of maple syrup urine disease.</strong>
Am. J. Dis. Child. 113: 68-73, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6015908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6015908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6015908" 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/archpedi.1967.02090160118014" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="65" class="mim-anchor"></a>
<a id="Tiu1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tiu, A. B., Naujokas, M., Eisenstein, R., Francke, U., Barton, D. E., Hoganson, G. E.
<strong>Cloning and chromosome mapping of a cDNA encoding the E1-alpha subunit of branched chain ketoacid dehydrogenase (BCKAD). (Abstract)</strong>
Am. J. Hum. Genet. 43: A17 only, 1988.
</p>
</div>
</li>
<li>
<a id="66" class="mim-anchor"></a>
<a id="Valman1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Valman, H. B., Patrick, H. B., Seakins, A. D., Platt, J. W., Gompertz, D.
<strong>Family with intermittent maple syrup urine disease.</strong>
Arch. Dis. Child. 48: 225-228, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4693464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4693464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4693464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.48.3.225" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="67" class="mim-anchor"></a>
<a id="Van Calcar1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van Calcar, S. C., Harding, C. O., Davidson, S. R., Barness, L. A., Wolff, J. A.
<strong>Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia.</strong>
Am. J. Med. Genet. 44: 641-646, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1481826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1481826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1481826" 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/ajmg.1320440523" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="68" class="mim-anchor"></a>
<a id="Van der Horst1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van der Horst, J. L., Wadman, S. K.
<strong>A variant form of branched-chain keto aciduria: case report.</strong>
Acta Paediat. Scand. 60: 594-599, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5125167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5125167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5125167" 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.1651-2227.1971.tb06996.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="69" class="mim-anchor"></a>
<a id="Westall1957" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Westall, R. G., Dancis, J., Miller, S.
<strong>Maple syrup urine disease.</strong>
Am. J. Dis. Child. 94: 571-572, 1957.
</p>
</div>
</li>
<li>
<a id="70" class="mim-anchor"></a>
<a id="Wong1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wong, P. W. K., Justice, P., Smith, G. F., Hsia, D. Y.-Y.
<strong>A case of classical maple syrup urine disease, 'thiamine non-responsive'.</strong>
Clin. Genet. 3: 27-33, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5066975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5066975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5066975" 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.1399-0004.1972.tb01722.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="71" class="mim-anchor"></a>
<a id="Woody1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Woody, N. C., Harris, J. A.
<strong>Family screening studies in maple syrup urine disease (branched-chain ketoaciduria).</strong>
J. Pediat. 66: 1042-1048, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14288457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14288457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14288457" 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/s0022-3476(65)80090-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="72" class="mim-anchor"></a>
<a id="Wu2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wu, J.-Y., Kao, H.-J., Li, S.-C., Stevens, R., Hillman, S., Millington, D., Chen, Y.-T.
<strong>ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease.</strong>
J. Clin. Invest. 113: 434-440, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14755340[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=14755340" 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/JCI19574" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="73" class="mim-anchor"></a>
<a id="Zhang1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhang, B., Edenberg, H. J., Crabb, D. W., Harris, R. A.
<strong>Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.</strong>
J. Clin. Invest. 83: 1425-1429, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2703538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2703538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2703538" 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/JCI114033" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="74" class="mim-anchor"></a>
<a id="Zhang1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhang, B., Wappner, R. S., Brandt, I. K., Harris, R. A., Crabb, D. W.
<strong>Sequence of the E1-alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease.</strong>
Am. J. Hum. Genet. 46: 843-846, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2316528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2316528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2316528" 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="75" class="mim-anchor"></a>
<a id="Zhang1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhang, B., Zhao, Y., Harris, R. A., Crabb, D. W.
<strong>Molecular defects in the E1-alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.</strong>
Molec. Biol. Med. 8: 39-47, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1943689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1943689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1943689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</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">
Ada Hamosh - updated : 02/09/2024
</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 : 06/18/2018<br>Cassandra L. Kniffin - updated : 3/26/2013<br>Cassandra L. Kniffin - updated : 2/28/2013<br>Cassandra L. Kniffin - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 2/29/2008<br>Cassandra L. Kniffin - updated : 6/14/2007<br>Cassandra L. Kniffin - updated : 4/25/2007<br>Cassandra L. Kniffin - updated : 4/16/2004<br>Natalie E. Krasikov - updated : 3/29/2004<br>Natalie E. Krasikov - updated : 2/19/2004<br>Cassandra L. Kniffin - reorganized : 1/28/2004<br>Cassandra L. Kniffin - updated : 12/29/2003<br>Victor A. McKusick - updated : 8/21/2003<br>Ada Hamosh - updated : 2/13/2002<br>Ada Hamosh - updated : 2/6/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 10/15/1999<br>Victor A. McKusick - updated : 2/12/1998
</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">
Victor A. McKusick : 6/4/1986
</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">
carol : 03/01/2024
</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">
carol : 02/12/2024<br>carol : 02/09/2024<br>carol : 02/09/2024<br>alopez : 07/12/2018<br>carol : 06/19/2018<br>alopez : 06/18/2018<br>carol : 09/09/2016<br>carol : 07/09/2016<br>carol : 3/31/2013<br>ckniffin : 3/26/2013<br>carol : 3/7/2013<br>carol : 3/5/2013<br>ckniffin : 2/28/2013<br>terry : 5/30/2012<br>carol : 5/23/2012<br>terry : 3/27/2012<br>terry : 3/27/2012<br>carol : 7/22/2011<br>carol : 10/26/2010<br>terry : 5/11/2010<br>wwang : 11/6/2009<br>ckniffin : 11/2/2009<br>terry : 3/5/2009<br>wwang : 3/4/2008<br>ckniffin : 2/29/2008<br>wwang : 6/27/2007<br>ckniffin : 6/14/2007<br>wwang : 5/1/2007<br>ckniffin : 4/25/2007<br>alopez : 6/13/2005<br>terry : 4/20/2005<br>terry : 2/10/2005<br>ckniffin : 8/24/2004<br>ckniffin : 4/16/2004<br>carol : 4/1/2004<br>terry : 3/29/2004<br>carol : 2/19/2004<br>terry : 2/19/2004<br>ckniffin : 1/28/2004<br>carol : 1/28/2004<br>ckniffin : 12/29/2003<br>carol : 8/26/2003<br>tkritzer : 8/25/2003<br>tkritzer : 8/22/2003<br>terry : 8/21/2003<br>alopez : 2/13/2002<br>terry : 2/13/2002<br>mcapotos : 2/12/2001<br>mcapotos : 2/8/2001<br>terry : 2/6/2001<br>carol : 1/24/2001<br>terry : 1/23/2001<br>carol : 10/18/1999<br>carol : 10/15/1999<br>carol : 6/1/1999<br>carol : 6/19/1998<br>dholmes : 5/11/1998<br>carol : 4/24/1998<br>mark : 2/18/1998<br>terry : 2/12/1998<br>mark : 11/19/1997<br>jenny : 11/19/1997<br>carol : 6/23/1997<br>mark : 6/16/1997<br>mark : 10/31/1995<br>carol : 10/19/1994<br>davew : 8/19/1994<br>mimadm : 3/29/1994<br>carol : 11/23/1993<br>carol : 12/18/1992
</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> 248600
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
MAPLE SYRUP URINE DISEASE, TYPE IA; MSUD1A
</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">
MAPLE SYRUP URINE DISEASE; MSUD<br />
BRANCHED-CHAIN KETOACIDURIA<br />
BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY<br />
BCKD DEFICIENCY<br />
KETO ACID DECARBOXYLASE DEFICIENCY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>ORPHA:</strong> 268145, 268162, 268173, 268184, 511; &nbsp;
<strong>DO:</strong> 9269; &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">
19q13.2
</span>
</td>
<td>
<span class="mim-font">
Maple syrup urine disease, type Ia
</span>
</td>
<td>
<span class="mim-font">
248600
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
BCKDHA
</span>
</td>
<td>
<span class="mim-font">
608348
</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 maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).</p><p>The classic form, which comprises 75% of MSUD patients, is manifested within the first 2 weeks of life with poor feeding, lethargy, seizures, coma, and death if untreated. Intermediate MSUD is associated with elevated BCAAs and BCKA, with progressive mental retardation and developmental delay without a history of catastrophic illness. The diagnosis is usually delayed for many months. An intermittent form of MSUD may have normal levels of BCAAs, normal intelligence and development until a stress, e.g., infection, precipitates decompensation with ketoacidosis and neurologic symptoms, which are usually reversed with dietary treatment. Thiamine-responsive MSUD is similar to the intermediate phenotype but responds to pharmacologic doses of thiamine with normalization of BCAAs. The E3-deficient MSUD is caused by defects in the dehydrogenase (E3) component of the BCKAD complex that is common to the pyruvate and alpha-ketoglutarate dehydrogenase complexes. Patients with E3 deficiency have dysfunction of all 3 enzyme complexes, and patients usually die in infancy with severe lactic acidosis (summary by Chuang et al., 1995). </p><p><strong><em>Genetic Heterogeneity of Maple Syrup Urine Disease</em></strong></p><p>
MSUD1B (620698) is caused by mutation in the BCKDHB gene (248611) on chromosome 6q14, and MSUD2 (620699) is caused by mutation in the DBT gene (248610) on chromosome 1p21.</p><p>Mutation in the E3 component of the BCKDC complex, DLD (238331), on chromosome 7q31, causes an overlapping but more severe phenotype known as dihydrolipoamide dehydrogenase deficiency (DLDD; 246900). DLDD is sometimes referred to as MSUD3.</p><p>See also a mild variant of MSUD (MSUDMV; 615135), caused by mutation in the regulatory gene PPM1K (611065).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Early Reports of Classic MSUD</em></strong></p><p>
In classic MSUD, which is the most common form of the disorder, 50% or more of the keto acids are derived from leucine, and the activity of the BCKD complex is less than 2% of normal. Affected newborns appear normal at birth, with symptoms developing between 4 and 7 days of age. The infants show lethargy, weight loss, metabolic derangement, and progressive neurologic signs of altering hypotonia and hypertonia, reflecting a severe encephalopathy. Seizures and coma usually occur, followed by death if untreated (Chuang and Shih, 2001).</p><p>Menkes et al. (1954) reported a familial syndrome in which 4 sibs had progressive infantile cerebral dysfunction associated with an unusual urinary substance. Onset was in the first week of life, with death by 3 months of age. The urine had an odor resembling maple syrup. Referring to the syndrome as 'maple syrup urine disease,' Westall et al. (1957) found that the levels of branched-chain amino acids, leucine, isoleucine, and valine, were greatly elevated. Menkes (1959) isolated and identified the corresponding keto acids in the urine of affected patients, suggesting that the catabolic pathways of the branched-chain amino acids were blocked at the decarboxylation step. Dancis et al. (1960) also referred to the disorder as 'branched-chain ketoaciduria.' </p><p>Wong et al. (1972) reported a case of classic MSUD. DiGeorge et al. (1982) made important observations on the course of classic MSUD in the first 4 days of life when an affected child was on a diet devoid of branched-chain amino acids. Although the branched-chain amino acids were normal in cord blood, serum leucine was significantly elevated by 4 to 14 hours of age and rose progressively thereafter, permitting an accurate and early diagnosis. However, Shih (1984) emphasized that classic MSUD may be missed in newborn screening because of slow rise of blood leucine levels. </p><p>Frezal et al. (1985) observed a family in which 2 different forms of MSUD occurred. The proposita had an acute neonatal form; 2 of her sisters had an almost asymptomatic form which the authors thought represented compound heterozygosity for the classic mutant and a partial variant. The proband did not respond to thiamine. </p><p><strong><em>Early Reports of Intermediate MSUD</em></strong></p><p>
Schulman et al. (1970) first described intermediate MSUD in a 19-month-old patient who was being evaluated for mental retardation. She had normal physical growth but severe developmental delay. She had mild systemic acidosis and markedly increased levels of plasma branched-chain amino acids and urinary branched-chain keto acids. Protein restriction was effective, but thiamine administration was not. The patient had 15 to 25% residual BCKD activity in leukocytes and fibroblasts. Kalyanaraman et al. (1972) reported 2 patients with the intermediate form of MSUD manifesting as hyperkinetic behavior and mental retardation. </p><p>Chhabria et al. (1979) reported a neonate who presented with ophthalmoplegia and was later found to have intermediate MSUD with residual BCKD complex activity. They noted that 2 similar cases with MSUD and ophthalmoplegia had previously been reported. </p><p>Gonzalez-Rios et al. (1985) reported a boy with intermediate MSUD who presented at age 10 months in ketoacidotic coma, with a history of irritability, poor feeding, and growth and developmental delay. Branched-chain amino acid restriction resulted in normal growth and development by age 42 months, but thiamine was not effective. The authors determined that the defect was in the catalytic activity of the E1 component of the BCKD complex, but there was some residual enzyme activity. </p><p>Schadewaldt et al. (2001) determined whole-body L-leucine oxidation in MSUD patients. In 4 patients with classic MSUD, L-leucine oxidation was too low to be measurable. In 2 females with a severe variant form of the disease, L-leucine oxidation was about 4% of control. In 6 milder variants, including intermediates, the estimates for residual whole-body L-leucine oxidation ranged from 19 to 86% (59 +/- 24%) of control, and were substantially higher than the residual branched-chain 2-oxo acid dehydrogenase complex activities in the patients' fibroblasts (10 to 25% of control). </p><p><strong><em>Early Reports of Intermittent MSUD</em></strong></p><p>
Morris et al. (1961) reported a 24-month-old female with intermittent MSUD. She was asymptomatic until age 16 months when she had recurrent episodic ataxia, lethargy, semicoma, and elevated urinary branched-chain keto acids following otitis media. Similarly, her younger brother was normal until about age 10 months when he had an acute episode. Dietary protein restriction was effective (see also Morris et al., 1966). </p><p>In 2 sibs of each of 2 families, Dancis et al. (1967) observed intermittent MSUD. The children suffered from a transient neurologic disorder associated with elevation of branched-chain amino acids and keto acids in the urine as well as a distinctive odor to the urine. One sib of each family died during an attack. Late onset of symptoms and clinical normality between attacks differentiated the condition from classic MSUD. In addition, the level of leukocyte BCKD complex activity seemed to be higher than in the classic form of the disease. </p><p>Two Norwegian families with the intermittent form were described by Goedde et al. (1970). They noted that in the intermittent form, only 1 parent shows decreased enzyme activity. </p><p>Van der Horst and Wadman (1971) described an intermittent form with severe episodes of acidosis with mental retardation that was partially reversed on dietary therapy. Other cases of intermittent MSUD were reported by Kiil and Rokkones (1964), Valman et al. (1973), and Indo et al. (1988). </p><p><strong><em>Early Reports of Thiamine-responsive MSUD</em></strong></p><p>
Scriver et al. (1971) described a variant of MSUD in which the hyperaminoacidemia was completely corrected by thiamine hydrochloride (10 mg per day) with dietary restriction (see also Scriver et al., 1985). Duran et al. (1978) and Duran and Wadman (1985) reported successful treatment of MSUD with thiamine administration. </p><p>Chuang et al. (1982) found that BCKDH complex activity in thiamine-responsive MSUD is about 30 to 40% the normal rate. Further studies showed that the primary defect in thiamine-responsive MSUD is reduced affinity of the mutant BCKD for thiamine pyrophosphate. </p><p>In 2 cases of MSUD responsive to thiamine administration, Zhang et al. (1990) found that the sequence of the gene for the E1-alpha subunit was normal. The result was considered consistent with any of the following possibilities: that the thiamine-binding site involves the E1-beta subunit, that the binding site is on E1-alpha, but a mutation elsewhere in the complex alters the affinity of the thiamine-binding site by an allosteric interaction, or that the clinical response to thiamine is due to stabilization of the enzyme that has a mutation in either the E1-beta or the E2 protein. </p><p><strong><em>Fenugreek Tea</em></strong></p><p>
In a report from Tunisia, Monastiri et al. (1997) noted that since maple syrup is largely unknown by Mediterranean populations, the odor of the urine in MSUD is more reminiscent of fenugreek (Trigonella foenum graecum L.) than of maple syrup. Fenugreek beans are traditionally used by Mediterranean populations as an infusion for sick persons (Boukef et al., 1982), and its fragrant smell is disagreeable and well known in that area. Monastiri et al. (1997) suggested that physicians in Mediterranean countries should keep in mind that a fenugreek odor of urine with neurologic distress in newborn infants, without a history of fenugreek ingestion by the mother of the baby, should raise a suspicion of MSUD. </p><p>Sewell et al. (1999) described a case of 'pseudo-maple syrup urine disease' caused by drinking fenugreek tea. The 5-week-old Egyptian infant had a 10-minute episode of unconsciousness while drinking bottled tea. He recovered spontaneously, but the parents nevertheless sought medical attention. On examination, the child was found to exude an aroma similar to that of Maggi (a widely available flavoring), and a spontaneously voided urine sample had a similar aroma. The parents indicated that the child had been given herbal tea (Helba tea) to reduce flatulence and prevent fever. This tea contains seeds of fenugreek. Analysis of the infant's urine revealed the presence of sotolone, the compound responsible for the aroma in maple syrup urine disease (Podebrad et al., 1999). Tea prepared from fenugreek seeds was found to contain sotolone. Bartley et al. (1981) had reported a similar case. Since herbal teas are popular as home remedies, particularly in Middle Eastern countries, physicians should use caution when they are presented with young infants from such countries, to avoid unnecessary and costly investigations. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Kaplan et al. (1989) described psychometric testing on 9 girls and 7 boys with MSUD. They concluded that prospective or early treatment significantly improves the intellectual outcome and that poor biochemical control may adversely affect performance.</p><p>Van Calcar et al. (1992) described a 25-year-old woman with classic MSUD who was diagnosed at the age of 11 days and was successfully treated with dietary restrictions. She was followed closely during a pregnancy, with delivery of a healthy baby whose length and weight were at the 5th centile. </p><p>Bodner-Leidecker et al. (2000) reported a patient with classic MSUD who had orthotopic liver transplantation at age 7 years due to a terminal liver failure triggered by a hepatitis A infection. The patient was maintained on an unrestricted diet, and plasma concentrations of branched-chain L-amino and 2-oxo acids were stable, yet at moderately increased levels (2- to 3-fold of control). L-alloisoleucine concentrations, however, remained remarkably elevated (greater than 5-fold of control). In vivo catabolism showed normal rates of L-alloisoleucine and leucine elimination. Bodner-Leidecker et al. (2000) suggested that the enhanced substrate supply from extrahepatic sources was responsible for the elevation of plasma concentrations. </p><p>Morton et al. (2002) reported 35 Mennonite patients with MSUD and homozygosity for the Y393N mutation (608348.0001) in the BCKDHA gene and 1 non-Mennonite patient who was compound heterozygous for the Y393N mutation and a splice-site mutation. Using amino acid analysis of plasma or whole blood collected on filter paper, they identified 18 affected neonates between 12 and 24 hours of age. None of the infants identified before 3 days of age and managed according to the protocol suggested by the authors became ill during the neonatal period. MSUD was diagnosed after age 3 days in 18 infants, all of whom had the characteristic maple syrup-like odor and neurologic deficits, including dystonic posturing, seizures, and cerebral edema. Follow-up of all 36 patients showed that the overall rate of hospitalization after the neonatal period was only 0.56 days per patient per year (25% of which was accounted for by 2 patients), and all showed uniformly good developmental outcomes. Four patients developed life-threatening cerebral edema as a consequence of infection and metabolism intoxication, but all recovered. Morton et al. (2002) presented a detailed treatment protocol for MSUD that was designed to inhibit endogenous protein catabolism, sustain protein synthesis, prevent amino acid deficiencies, and maintain normal serum osmolarity. The authors emphasized the importance of diagnosis within the first days of life and concluded that classic MSUD can be properly managed to allow a benign neonatal course, normal growth and development, and low hospitalization rates. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Genetic Heterogeneity</em></strong></p><p>
Lyons et al. (1973) sought genetic heterogeneity in maple syrup urine disease by the study of heterokaryons derived from cultured fibroblasts of different patients. Fibroblasts from one patient consistently complemented those from other particular patients by increasing the level of BCKD. Correlation with clinical expression could not be made. Singh et al. (1977) and Jinno et al. (1984) likewise did complementation analysis to answer the question of genetic heterogeneity. Jinno et al. (1984) demonstrated the usefulness of lymphoid cell lines in such studies and found 2 complementation groups. Unlike the earlier 2 studies, the 2 groups corresponded to clinical groups: 3 cell lines were from patients with the variant type and 2 were from patients with the classic type. </p><p>Indo et al. (1988) found altered BCKDH complex enzyme activity and kinetics that appeared to correspond with MSUD phenotype: classic, intermediate, and intermittent types of MSUD demonstrated increasing levels of complex activity, and were associated with sigmoidal, near-sigmoidal, and hyperbolic kinetics, respectively. </p><p>By Northern and Western blot analysis of the E1-alpha and E2 proteins in cell cultures from 7 unrelated MSUD patients, Fisher et al. (1989) demonstrated several distinct molecular phenotypes according to mRNA and protein-subunit contents, demonstrating the genetic complexity of MSUD. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The transmission pattern of MSUD1A in the family reported by Zhang et al. (1989, 1991) and Chuang et al. (1994) was consistent with autosomal recessive inheritance. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a patient with classic MSUD, Zhang et al. (1989, 1991) identified a mutation in the gene encoding the E1-alpha subunit (608348.0001). Chuang et al. (1994) later identified a second mutation in the BCKDHA gene in this patient (608348.0002). Each parent was heterozygous for 1 of the mutations. </p><p>In 3 of 4 unrelated Hispanic-Mexican patients with intermediate MSUD, Chuang et al. (1995) identified a homozygous mutation in the BCKDHA gene (608348.0003). The fourth patient was homozygous for a different mutation in the BCKDHA gene (608348.0004). </p><p>Patel and Harris (1995) provided a schematic representation of 7 point mutations, 1 small deletion, and 1 small insertion reported in the BCKDHA gene. </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>Nellis et al. (2003) evaluated and compared the clinical course of 11 unrelated patients with MSUD, including 3 with mutations in the E1-alpha gene, 5 with mutations in the E1-beta gene, and 3 with mutations in the E2 gene (2 were sibs). All had residual BCKD activity less than 3% of control values. All patients except 2, 1 with E1-alpha and 1 with an E1-beta mutations, had documented episodes of metabolic decompensation. IQ greater than 90 was observed in 70% of patients. Patients with mutations in the E1-alpha gene tended to have decreased IQs compared to other patients. In general, however, the results indicated no significant impact of 1 mutant locus to another in determining clinical outcome. The most important factor in determining outcome was early identification and institution of a protein-modified diet. </p><p>Among 15 patients with variant forms of MSUD, Flaschker et al. (2007) found that more severe phenotypes tended to be associated with mutations in the BCKDHA gene, whereas milder variants tended to be associated with mutations in the BCKDHB and DBT genes. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a mobile, urban, predominantly white population of New England, Levy (1973) found a frequency of MSUD of 1 in 290,000 on newborn screening. </p><p>The highest reported frequency of MSUD was observed among the Old Order Mennonites of Pennsylvania (Auerbach and DiGeorge, 1973; Naylor, 1980; Marshall and DiGeorge, 1981). In conservative Mennonites of eastern Pennsylvania, classic MSUD has a frequency as high as 1 in 176 births (DiGeorge et al., 1982). Matsuda et al. (1990) demonstrated the specific defect in the Mennonite cases (see 608348.0001). </p><p>Chuang and Shih (2001) noted a worldwide incidence of MSUD of 1 in 185,000 live births.</p><p>Using complementation assays in cells from 63 individuals with clinically diagnosed MSUD, Nellis and Danner (2001) found that 33% of the cases were caused by mutations in the E1-alpha gene, 38% by mutations in the E1-beta gene, and 19% by mutations in the E2 gene. Ten percent of the tested cell lines gave ambiguous results by showing no complementation or restoration of activity with 2 gene products. </p><p>In 11 children with MSUD from a Gypsy community in southern Portugal, Quental et al. (2008) identified a homozygous 1-bp deletion (117delC; 608348.0009) in the BCKDHA gene. By haplotype analysis, Quental et al. (2009) showed that the 117delC mutation is a founder mutation in Portuguese Gypsies with a carrier frequency estimated to be 1.4%. An unrelated Spanish patient with the deletion who was not of Gypsy origin did not share the haplotype, indicating that it occurred independently. The deletion occurs within a poly-C tract and may represent a mutation hotspot in the BCKDHA gene. </p><p>Feuchtbaum et al. (2012) reported the birth rates of selected metabolic, endocrine, hemoglobin, and cystic fibrosis disorders for specific racial/ethnic groups in a total of 2,282,138 newborns born between 2005 and 2010 in California who were screened using a blood sample collected via heel stick. Screening of 21,973 individuals of Middle Eastern ancestry gave an estimated birth prevalence for maple syrup urine disease of approximately 14 per 100,000 births; of 61,120 individuals of Filipino ancestry, approximately 2 per 100,000 births; and of 1,183,044 Hispanic individuals, approximately 1 per 100,000 births. Results for other ethnic groups were less than 1 per 100,000 births. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In polled Hereford calves with maple syrup urine disease, Zhang et al. (1991) demonstrated a C-to-T substitution in the E1-alpha gene that introduced a stop codon into the leader peptide of the protein. </p><p>Gortz et al. (2003) found that spontaneous network activity in primary dissociated embryonic rat neurons was reversibly reduced or blocked by increased extracellular leucine or alpha-ketoisocaproate in a dose-dependent fashion. In contrast, resting potential, various membrane currents, and intracellular calcium were unaffected by the substances. Gortz et al. (2003) concluded that an abnormality of release or imbalance of concentration of glutaminergic/GABAergic neurotransmitters causes the acute neuronal dysfunction in maple syrup urine disease. </p><p>In a large N-ethyl-N-nitrosourea (ENU)-induced mouse mutagenesis program, Wu et al. (2004) identified a phenotype characterized by striking elevation of serum branched-chain amino acids and a moderate increase in arginine. Clinically, the affected mice also showed failure to thrive, weakness, decreased spontaneous movement, and thin hair, features seen in humans with maple syrup urine disease. In the affected mice, Wu et al. (2004) identified a homozygous T-to-C transition in the 5-prime splicing site consensus sequence of exon 2 and intron 2 of the Bcat2 gene (113530), resulting in deletion of exon 2. RT-PCR showed markedly reduced amounts of Bcat2 mRNA in muscle and liver compared to controls. The authors noted that exon 2 contains the mitochondrial targeting leader sequence. A diet low in branched-chain amino acids resulted in clinical improvement in the mice. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Chuang et al. (1982); Chuang et al. (1982); Dancis et al. (1963);
Danner et al. (1985); Danner et al. (1978); Fekete et al. (1989);
Fisher et al. (1991); Goedde et al. (1968); Heffelfinger et al.
(1983); Heffelfinger et al. (1984); Hong et al. (1996); Naughten et
al. (1982); Norton et al. (1962); Snyderman (1967); Tiu et al.
(1988); Woody and Harris (1965)
</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">
Auerbach, V. H., DiGeorge, A.
<strong>Maple syrup urine disease. In: Hommes, F. A.; Van den Berg, C. J. (eds.): Inborn Errors of Metabolism.</strong>
London: Academic Press (pub.) 1973. P. 337.
</p>
</li>
<li>
<p class="mim-text-font">
Bartley, G. B., Hilty, M. D., Andreson, B. D., Clairmont, A. C., Maschke, S. P.
<strong>&#x27;Maple-syrup&#x27; urine odor due to fenugreek ingestion.</strong>
New Eng. J. Med. 305: 467 only, 1981.
[PubMed: 7254294]
[Full Text: https://doi.org/10.1056/NEJM198108203050823]
</p>
</li>
<li>
<p class="mim-text-font">
Bodner-Leidecker, A., Wendel, U., Saudubray, J.-M., Schadewaldt, P.
<strong>Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation.</strong>
J. Inherit. Metab. Dis. 23: 805-818, 2000.
[PubMed: 11196106]
[Full Text: https://doi.org/10.1023/a:1026708618507]
</p>
</li>
<li>
<p class="mim-text-font">
Boukef, K., Souissi, H. R., Balansard, G.
<strong>Contribution a l&#x27; etude des plantes utilisees en medecine traditionnelle Tunisienne.</strong>
Plantes medicinales Phytotherapie 16: 260-279, 1982.
</p>
</li>
<li>
<p class="mim-text-font">
Chhabria, S., Tomasi, L. G., Wong, W. K.
<strong>Ophthalmoplegia and bulbar palsy in a variant form of maple syrup urine disease.</strong>
Ann. Neurol. 6: 71-72, 1979.
[PubMed: 507761]
[Full Text: https://doi.org/10.1002/ana.410060118]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Cox, R. P.
<strong>Biochemical basis of thiamin-responsive maple syrup urine disease.</strong>
Trans. Assoc. Am. Phys. 95: 196-204, 1982.
[PubMed: 7182976]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Cox, R. P.
<strong>Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate.</strong>
Proc. Nat. Acad. Sci. 79: 3300-3304, 1982.
[PubMed: 6954481]
[Full Text: https://doi.org/10.1073/pnas.79.10.3300]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, D. T., Ku, L. S., Kerr, D. S., Cox, R. P.
<strong>Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures.</strong>
Am. J. Hum. Genet. 34: 416-424, 1982.
[PubMed: 7081220]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, D. T., Shih, V. E.
<strong>Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005.
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, J. L., Davie, J. R., Chinsky, J. M., Wynn, R. M., Cox, R. P., Chuang, D. T.
<strong>Molecular and biochemical basis of intermediate maple syrup urine disease: occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of Hispanic-Mexican patients.</strong>
J. Clin. Invest. 95: 954-963, 1995.
[PubMed: 7883996]
[Full Text: https://doi.org/10.1172/JCI117804]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, J. L., Fisher, C. R., Cox, R. P., Chuang, D. T.
<strong>Molecular basis of maple syrup urine disease: novel mutations at the E1-alpha locus that impair E1(alpha-2-beta-2) assembly or decrease steady-state E1-alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.</strong>
Am. J. Hum. Genet. 55: 297-304, 1994.
[PubMed: 8037208]
</p>
</li>
<li>
<p class="mim-text-font">
Dancis, J., Hutzler, J., Levitz, M.
<strong>The diagnosis of maple syrup disease (branched chain ketoaciduria) by the in vitro study of the peripheral leukocyte.</strong>
Pediatrics 32: 234-238, 1963.
[PubMed: 14044451]
</p>
</li>
<li>
<p class="mim-text-font">
Dancis, J., Hutzler, J., Rokkones, T.
<strong>Intermittent branched-chain ketonuria: variant of maple-syrup-urine disease.</strong>
New Eng. J. Med. 276: 84-89, 1967.
[PubMed: 6015521]
[Full Text: https://doi.org/10.1056/NEJM196701122760204]
</p>
</li>
<li>
<p class="mim-text-font">
Dancis, J., Levitz, M., Westall, R. G.
<strong>Maple syrup urine disease: branched-chain ketoaciduria.</strong>
Pediatrics 25: 72-79, 1960.
[PubMed: 13813934]
</p>
</li>
<li>
<p class="mim-text-font">
Danner, D. J., Armstrong, N., Heffelfinger, S. C., Sewell, E. T., Priest, J. H., Elsas, L. J.
<strong>Absence of branched chain acyl-transferase as a cause of maple syrup urine disease.</strong>
J. Clin. Invest. 75: 858-860, 1985.
[PubMed: 3980729]
[Full Text: https://doi.org/10.1172/JCI111783]
</p>
</li>
<li>
<p class="mim-text-font">
Danner, D. J., Wheeler, F. B., Lemmon, S. K., Elsas, L. J., II.
<strong>In vivo and in vitro response of human branched chain alpha-ketoacid thiamine pyrophosphate.</strong>
Pediat. Res. 12: 235-238, 1978.
[PubMed: 643394]
[Full Text: https://doi.org/10.1203/00006450-197803000-00016]
</p>
</li>
<li>
<p class="mim-text-font">
DiGeorge, A. M., Rezvani, I., Garibaldi, L. R., Schwartz, M.
<strong>Prospective study of maple-syrup-urine disease for the first four days of life.</strong>
New Eng. J. Med. 307: 1492-1495, 1982.
[PubMed: 7144815]
[Full Text: https://doi.org/10.1056/NEJM198212093072405]
</p>
</li>
<li>
<p class="mim-text-font">
Duran, M., Tielens, A. G. M., Wadman, S. K., Stigter, J. C. M., Kleijer, W. J.
<strong>Effects of thiamine in a patient with a variant form branched-chain ketoaciduria.</strong>
Acta Paediat. Scand. 67: 367-372, 1978.
[PubMed: 654914]
[Full Text: https://doi.org/10.1111/j.1651-2227.1978.tb16336.x]
</p>
</li>
<li>
<p class="mim-text-font">
Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.
[PubMed: 3930844]
[Full Text: https://doi.org/10.1007/BF01800663]
</p>
</li>
<li>
<p class="mim-text-font">
Fekete, G., Plattner, R., Crabb, D. W., Zhang, B., Harris, R. A., Heerema, N., Palmer, C. G.
<strong>Localization of the human gene for the E1-alpha subunit of branched chain keto acid dehydrogenase (BCKDHA) to chromosome 19q13.1-q13.2.</strong>
Cytogenet. Cell Genet. 50: 236-237, 1989.
[PubMed: 2805821]
[Full Text: https://doi.org/10.1159/000132768]
</p>
</li>
<li>
<p class="mim-text-font">
Feuchtbaum, L., Carter, J., Dowray, S., Currier, R. J., Lorey, F.
<strong>Birth prevalence of disorders detectable through newborn screening by race/ethnicity.</strong>
Genet. Med. 14: 937-945, 2012.
[PubMed: 22766612]
[Full Text: https://doi.org/10.1038/gim.2012.76]
</p>
</li>
<li>
<p class="mim-text-font">
Fisher, C. W., Chuang, J. L., Griffin, T. A., Lau, K. S., Cox, R. P., Chuang, D. T.
<strong>Molecular phenotypes in cultured maple syrup urine disease cells: complete E(1)-alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex.</strong>
J. Biol. Chem. 264: 3448-3453, 1989.
[PubMed: 2914958]
</p>
</li>
<li>
<p class="mim-text-font">
Fisher, C. W., Lau, K. S., Fisher, C. R., Wynn, R. M., Cox, R. P., Chuang, D. T.
<strong>A 17-bp insertion and a phe215-to-cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34.</strong>
Biochem. Biophys. Res. Commun. 174: 804-809, 1991.
[PubMed: 1847055]
[Full Text: https://doi.org/10.1016/0006-291x(91)91489-y]
</p>
</li>
<li>
<p class="mim-text-font">
Flaschker, N., Feyen, O., Fend, S., Simon, E., Schadewaldt, P., Wendel, U.
<strong>Description of the mutations in 15 subjects with variant forms of maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 30: 903-909, 2007.
[PubMed: 17922217]
[Full Text: https://doi.org/10.1007/s10545-007-0579-x]
</p>
</li>
<li>
<p class="mim-text-font">
Frezal, J., Amedee-Manesme, O., Mitchell, G., Heuertz, S., Rey, F., Rey, J., Saudubray, J. M.
<strong>Maple syrup urine disease: two different forms within a single family.</strong>
Hum. Genet. 71: 89-91, 1985.
[PubMed: 4029957]
[Full Text: https://doi.org/10.1007/BF00295676]
</p>
</li>
<li>
<p class="mim-text-font">
Goedde, H. W., Langenbeck, U., Brackertz, D., Keller, W., Rokkones, T., Halvorsen, S., Kiil, R., Merton, B.
<strong>Clinical and biochemical-genetic aspects of intermittent branched-chain ketoaciduria. Report of two Scandinavian families.</strong>
Acta Paediat. Scand. 59: 83-87, 1970.
[PubMed: 5452306]
[Full Text: https://doi.org/10.1111/j.1651-2227.1970.tb15519.x]
</p>
</li>
<li>
<p class="mim-text-font">
Goedde, H. W., Langenbeck, U., Brackertz, D.
<strong>Detection of heterozygotes in maple syrup urine disease: role of lymphocyte count.</strong>
Humangenetik 6: 189-190, 1968.
[PubMed: 5704438]
[Full Text: https://doi.org/10.1007/BF00297728]
</p>
</li>
<li>
<p class="mim-text-font">
Gonzalez-Rios, M. C., Chuang, D. T., Cox, R. P., Schmidt, K., Knopf, K., Packman, S.
<strong>A distinct variant of intermediate maple syrup urine disease.</strong>
Clin. Genet. 27: 153-159, 1985.
[PubMed: 3978850]
[Full Text: https://doi.org/10.1111/j.1399-0004.1985.tb00203.x]
</p>
</li>
<li>
<p class="mim-text-font">
Gortz, P., Koller, H., Schwahn, B., Wendel, U., Siebler, M.
<strong>Disturbance of cultured rat neuronal network activity depends on concentration and ratio of leucine and alpha-ketoisocaproate: implication for acute encephalopathy of maple syrup urine disease.</strong>
Pediat. Res. 53: 320-324, 2003.
[PubMed: 12538793]
[Full Text: https://doi.org/10.1203/01.PDR.0000047521.50656.16]
</p>
</li>
<li>
<p class="mim-text-font">
Heffelfinger, S. C., Sewell, E. T., Danner, D. J.
<strong>Identification of specific subunits of highly purified bovine liver branched chain ketoacid dehydrogenase.</strong>
Biochemistry 22: 5519-5522, 1983.
[PubMed: 6652074]
[Full Text: https://doi.org/10.1021/bi00293a011]
</p>
</li>
<li>
<p class="mim-text-font">
Heffelfinger, S. C., Sewell, E. T., Elsas, L. J., Danner, D. J.
<strong>Direct physical evidence for stabilization of branched-chain alpha-ketoacid dehydrogenase by thiamin pyrophosphate.</strong>
Am. J. Hum. Genet. 36: 802-807, 1984.
[PubMed: 6475955]
</p>
</li>
<li>
<p class="mim-text-font">
Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
Hum. Molec. Genet. 5: 1925-1930, 1996.
[PubMed: 8968745]
[Full Text: https://doi.org/10.1093/hmg/5.12.1925]
</p>
</li>
<li>
<p class="mim-text-font">
Indo, Y., Akaboshi, I., Nobukuni, Y., Endo, F., Matsuda, I.
<strong>Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity.</strong>
Hum. Genet. 80: 6-10, 1988.
[PubMed: 3417306]
[Full Text: https://doi.org/10.1007/BF00451447]
</p>
</li>
<li>
<p class="mim-text-font">
Jinno, Y., Akaboshi, I., Matsuda, I.
<strong>Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease.</strong>
Hum. Genet. 68: 54-56, 1984.
[PubMed: 6500555]
[Full Text: https://doi.org/10.1007/BF00293872]
</p>
</li>
<li>
<p class="mim-text-font">
Kalyanaraman, K., Chamukuttan, S., Arjundas, G., Gajanan, N., Ramamurthi, B.
<strong>Maple syrup urine disease (branched-chain keto-aciduria): variant type manifesting as hyperkinetic behaviour and mental retardation--report of two cases.</strong>
J. Neurol. Sci. 15: 209-218, 1972.
[PubMed: 5010106]
[Full Text: https://doi.org/10.1016/0022-510x(72)90008-1]
</p>
</li>
<li>
<p class="mim-text-font">
Kaplan, P., Mazur, A., Field, M.
<strong>Psychometric assessment in maple syrup urine disease: prospective, controlled pilot study. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A7 only, 1989.
</p>
</li>
<li>
<p class="mim-text-font">
Kiil, R., Rokkones, T.
<strong>Late manifesting variant of branched-chain ketoaciduria (maple syrup urine disease).</strong>
Acta Paediat. (Stockh.) 53: 356-364, 1964.
[PubMed: 14184314]
[Full Text: https://doi.org/10.1111/j.1651-2227.1964.tb07789.x]
</p>
</li>
<li>
<p class="mim-text-font">
Levy, H. L.
<strong>To genetic screening.</strong>
Adv. Hum. Genet. 4: 389-394, 1973.
[PubMed: 4783333]
</p>
</li>
<li>
<p class="mim-text-font">
Lyons, L. B., Cox, R. P., Dancis, J.
<strong>Complementation analysis of maple syrup urine disease in heterokaryons derived from cultured human fibroblasts.</strong>
Nature 243: 533-535, 1973.
[PubMed: 4355237]
[Full Text: https://doi.org/10.1038/243533a0]
</p>
</li>
<li>
<p class="mim-text-font">
Marshall, L., DiGeorge, A.
<strong>Maple syrup urine disease in the Old Order Mennonites. (Abstract)</strong>
Am. J. Hum. Genet. 33: 139A only, 1981.
</p>
</li>
<li>
<p class="mim-text-font">
Matsuda, I., Nobukuni, Y., Mitsubuchi, H., Indo, Y., Endo, F., Asaka, J., Harada, A.
<strong>A T-to-A substitution in the E1-alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite (sic) maple syrup urine disease patients.</strong>
Biochem. Biophys. Res. Commun. 172: 646-651, 1990.
[PubMed: 2241958]
[Full Text: https://doi.org/10.1016/0006-291x(90)90723-z]
</p>
</li>
<li>
<p class="mim-text-font">
Menkes, J. H., Hurst, P. L., Craig, J. M.
<strong>A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance.</strong>
Pediatrics 14: 462-467, 1954.
[PubMed: 13214961]
</p>
</li>
<li>
<p class="mim-text-font">
Menkes, J. H.
<strong>Maple syrup urine disease: isolation and identification of organic acids in the urine.</strong>
Pediatrics 23: 348-353, 1959.
[PubMed: 13633350]
</p>
</li>
<li>
<p class="mim-text-font">
Monastiri, K., Limame, K., Kaabachi, N., Kharrat, H., Bousnina, S., Pousse, H., Radhouane, M., Gueddiche, M. N., Snoussi, N.
<strong>Fenugreek odour in maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 20: 614-615, 1997.
[PubMed: 9266407]
[Full Text: https://doi.org/10.1023/a:1005335915708]
</p>
</li>
<li>
<p class="mim-text-font">
Morris, M. D., Fisher, D. A., Fiser, R.
<strong>Late-onset branched-chain ketoaciduria: (maple syrup urine disease).</strong>
J. Lancet 86: 149-152, 1966.
[PubMed: 5904649]
</p>
</li>
<li>
<p class="mim-text-font">
Morris, M. D., Lewis, B. D., Doolan, P. D., Harper, H. A.
<strong>Clinical and biochemical observations on an apparently nonfatal variant of branched-chain ketoaciduria (maple syrup urine disease).</strong>
Pediatrics 28: 918-923, 1961.
[PubMed: 14476272]
</p>
</li>
<li>
<p class="mim-text-font">
Morton, D. H., Strauss, K. A., Robinson, D. L., Puffenberger, E. G., Kelley, R. I.
<strong>Diagnosis and treatment of maple syrup disease: a study of 36 patients.</strong>
Pediatrics 109: 999-1008, 2002.
[PubMed: 12042535]
[Full Text: https://doi.org/10.1542/peds.109.6.999]
</p>
</li>
<li>
<p class="mim-text-font">
Naughten, E. R., Jenkins, J., Francis, D. E. M., Leonard, J. V.
<strong>Outcome of maple syrup urine disease.</strong>
Arch. Dis. Child. 57: 918-921, 1982.
[PubMed: 7181520]
[Full Text: https://doi.org/10.1136/adc.57.12.918]
</p>
</li>
<li>
<p class="mim-text-font">
Naylor, E. W.
<strong>Newborn screening for maple syrup urine disease (branched chain ketoaciduria). In: Bickel, H.; Guthrie, R.; Hammersen, G. (eds.): Neonatal Screening for Inborn Errors of Metabolism.</strong>
Berlin: Springer-Verlag (pub.) 1980. P. 19.
</p>
</li>
<li>
<p class="mim-text-font">
Nellis, M. M., Danner, D. J.
<strong>Gene preference in maple syrup urine disease.</strong>
Am. J. Hum. Genet. 68: 232-237, 2001.
[PubMed: 11112664]
[Full Text: https://doi.org/10.1086/316950]
</p>
</li>
<li>
<p class="mim-text-font">
Nellis, M. M., Kasinski, A., Carlson, M., Allen, R., Schaefer, A. M., Schwartz, E. M., Danner, D. J.
<strong>Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression.</strong>
Molec. Genet. Metab. 80: 189-195, 2003.
[PubMed: 14567968]
[Full Text: https://doi.org/10.1016/s1096-7192(03)00144-6]
</p>
</li>
<li>
<p class="mim-text-font">
Norton, P. M., Roitman, E., Snyderman, S. E., Holt, L. E., Jr.
<strong>A new finding in maple-syrup-urine disease.</strong>
Lancet 279: 26-27, 1962. Note: Originally Volume I.
[PubMed: 14480431]
[Full Text: https://doi.org/10.1016/s0140-6736(62)92646-6]
</p>
</li>
<li>
<p class="mim-text-font">
Patel, M. S., Harris, R. A.
<strong>Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.</strong>
FASEB J. 9: 1164-1172, 1995.
[PubMed: 7672509]
[Full Text: https://doi.org/10.1096/fasebj.9.12.7672509]
</p>
</li>
<li>
<p class="mim-text-font">
Podebrad, F., Heil, M., Reichert, S., Mosandl, A., Sewell, A. C., Bohles, H.
<strong>4,5-Dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease.</strong>
J. Inherit. Metab. Dis. 22: 107-114, 1999.
[PubMed: 10234605]
[Full Text: https://doi.org/10.1023/a:1005433516026]
</p>
</li>
<li>
<p class="mim-text-font">
Quental, S., Gusmao, A., Rodriguez-Pombo, P., Ugarte, M., Vilarinho, L., Amorim, A., Prata, M. J.
<strong>Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene.</strong>
Ann. Hum. Genet. 73: 298-303, 2009.
[PubMed: 19456321]
[Full Text: https://doi.org/10.1111/j.1469-1809.2009.00518.x]
</p>
</li>
<li>
<p class="mim-text-font">
Quental, S., Macedo-Ribeiro, S., Matos, R., Vilarinho, L., Martins, E., Teles, E. L., Rodrigues, E., Diogo, L., Garcia, P., Eusebio, F., Gaspar, A., Sequeira, S., Furtado, F., Lanca, I., Amorim, A., Prata, M. J.
<strong>Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community.</strong>
Molec. Genet. Metab. 94: 148-156, 2008.
[PubMed: 18378174]
[Full Text: https://doi.org/10.1016/j.ymgme.2008.02.008]
</p>
</li>
<li>
<p class="mim-text-font">
Schadewaldt, P., Bodner-Leidecker, A., Hammen, H.-W., Wendel, U.
<strong>Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease.</strong>
Pediat. Res. 49: 627-635, 2001.
[PubMed: 11328944]
[Full Text: https://doi.org/10.1203/00006450-200105000-00004]
</p>
</li>
<li>
<p class="mim-text-font">
Schulman, J. D., Lustberg, T. J., Kennedy, J. L., Museles, M., Seegmiller, J. E.
<strong>A new variant of maple syrup urine disease (branched-chain ketoaciduria): clinical and biochemical evaluation.</strong>
Am. J. Med. 49: 118-124, 1970.
[PubMed: 5431474]
[Full Text: https://doi.org/10.1016/s0002-9343(70)80121-8]
</p>
</li>
<li>
<p class="mim-text-font">
Scriver, C. R., Clow, C. L., George, H.
<strong>So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient.</strong>
J. Pediat. 107: 763-765, 1985.
[PubMed: 4056978]
[Full Text: https://doi.org/10.1016/s0022-3476(85)80413-3]
</p>
</li>
<li>
<p class="mim-text-font">
Scriver, C. R., MacKenzie, S., Clow, C. L., Delvin, E.
<strong>Thiamine-responsive maple-syrup-urine disease.</strong>
Lancet 297: 310-312, 1971. Note: Originally Volume I.
[PubMed: 4100151]
[Full Text: https://doi.org/10.1016/s0140-6736(71)91041-5]
</p>
</li>
<li>
<p class="mim-text-font">
Sewell, A. C., Mosandl, A., Bohles, H.
<strong>False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. (Letter)</strong>
New Eng. J. Med. 341: 769 only, 1999.
[PubMed: 10475807]
[Full Text: https://doi.org/10.1056/NEJM199909023411020]
</p>
</li>
<li>
<p class="mim-text-font">
Shih, V. E.
<strong>Maple-syrup-urine disease. (Letter)</strong>
New Eng. J. Med. 310: 596-597, 1984.
[PubMed: 6694715]
[Full Text: https://doi.org/10.1056/nejm198403013100916]
</p>
</li>
<li>
<p class="mim-text-font">
Singh, S., Willers, I., Goedde, H. W.
<strong>Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.</strong>
Clin. Genet. 11: 277-284, 1977.
[PubMed: 192504]
[Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb01313.x]
</p>
</li>
<li>
<p class="mim-text-font">
Snyderman, S. E.
<strong>The therapy of maple syrup urine disease.</strong>
Am. J. Dis. Child. 113: 68-73, 1967.
[PubMed: 6015908]
[Full Text: https://doi.org/10.1001/archpedi.1967.02090160118014]
</p>
</li>
<li>
<p class="mim-text-font">
Tiu, A. B., Naujokas, M., Eisenstein, R., Francke, U., Barton, D. E., Hoganson, G. E.
<strong>Cloning and chromosome mapping of a cDNA encoding the E1-alpha subunit of branched chain ketoacid dehydrogenase (BCKAD). (Abstract)</strong>
Am. J. Hum. Genet. 43: A17 only, 1988.
</p>
</li>
<li>
<p class="mim-text-font">
Valman, H. B., Patrick, H. B., Seakins, A. D., Platt, J. W., Gompertz, D.
<strong>Family with intermittent maple syrup urine disease.</strong>
Arch. Dis. Child. 48: 225-228, 1973.
[PubMed: 4693464]
[Full Text: https://doi.org/10.1136/adc.48.3.225]
</p>
</li>
<li>
<p class="mim-text-font">
Van Calcar, S. C., Harding, C. O., Davidson, S. R., Barness, L. A., Wolff, J. A.
<strong>Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia.</strong>
Am. J. Med. Genet. 44: 641-646, 1992.
[PubMed: 1481826]
[Full Text: https://doi.org/10.1002/ajmg.1320440523]
</p>
</li>
<li>
<p class="mim-text-font">
Van der Horst, J. L., Wadman, S. K.
<strong>A variant form of branched-chain keto aciduria: case report.</strong>
Acta Paediat. Scand. 60: 594-599, 1971.
[PubMed: 5125167]
[Full Text: https://doi.org/10.1111/j.1651-2227.1971.tb06996.x]
</p>
</li>
<li>
<p class="mim-text-font">
Westall, R. G., Dancis, J., Miller, S.
<strong>Maple syrup urine disease.</strong>
Am. J. Dis. Child. 94: 571-572, 1957.
</p>
</li>
<li>
<p class="mim-text-font">
Wong, P. W. K., Justice, P., Smith, G. F., Hsia, D. Y.-Y.
<strong>A case of classical maple syrup urine disease, &#x27;thiamine non-responsive&#x27;.</strong>
Clin. Genet. 3: 27-33, 1972.
[PubMed: 5066975]
[Full Text: https://doi.org/10.1111/j.1399-0004.1972.tb01722.x]
</p>
</li>
<li>
<p class="mim-text-font">
Woody, N. C., Harris, J. A.
<strong>Family screening studies in maple syrup urine disease (branched-chain ketoaciduria).</strong>
J. Pediat. 66: 1042-1048, 1965.
[PubMed: 14288457]
[Full Text: https://doi.org/10.1016/s0022-3476(65)80090-7]
</p>
</li>
<li>
<p class="mim-text-font">
Wu, J.-Y., Kao, H.-J., Li, S.-C., Stevens, R., Hillman, S., Millington, D., Chen, Y.-T.
<strong>ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease.</strong>
J. Clin. Invest. 113: 434-440, 2004.
[PubMed: 14755340]
[Full Text: https://doi.org/10.1172/JCI19574]
</p>
</li>
<li>
<p class="mim-text-font">
Zhang, B., Edenberg, H. J., Crabb, D. W., Harris, R. A.
<strong>Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.</strong>
J. Clin. Invest. 83: 1425-1429, 1989.
[PubMed: 2703538]
[Full Text: https://doi.org/10.1172/JCI114033]
</p>
</li>
<li>
<p class="mim-text-font">
Zhang, B., Wappner, R. S., Brandt, I. K., Harris, R. A., Crabb, D. W.
<strong>Sequence of the E1-alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease.</strong>
Am. J. Hum. Genet. 46: 843-846, 1990.
[PubMed: 2316528]
</p>
</li>
<li>
<p class="mim-text-font">
Zhang, B., Zhao, Y., Harris, R. A., Crabb, D. W.
<strong>Molecular defects in the E1-alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.</strong>
Molec. Biol. Med. 8: 39-47, 1991.
[PubMed: 1943689]
</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">
Ada Hamosh - updated : 02/09/2024<br>Ada Hamosh - updated : 06/18/2018<br>Cassandra L. Kniffin - updated : 3/26/2013<br>Cassandra L. Kniffin - updated : 2/28/2013<br>Cassandra L. Kniffin - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 2/29/2008<br>Cassandra L. Kniffin - updated : 6/14/2007<br>Cassandra L. Kniffin - updated : 4/25/2007<br>Cassandra L. Kniffin - updated : 4/16/2004<br>Natalie E. Krasikov - updated : 3/29/2004<br>Natalie E. Krasikov - updated : 2/19/2004<br>Cassandra L. Kniffin - reorganized : 1/28/2004<br>Cassandra L. Kniffin - updated : 12/29/2003<br>Victor A. McKusick - updated : 8/21/2003<br>Ada Hamosh - updated : 2/13/2002<br>Ada Hamosh - updated : 2/6/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 10/15/1999<br>Victor A. McKusick - updated : 2/12/1998
</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">
Victor A. McKusick : 6/4/1986
</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">
carol : 03/01/2024<br>carol : 02/12/2024<br>carol : 02/09/2024<br>carol : 02/09/2024<br>alopez : 07/12/2018<br>carol : 06/19/2018<br>alopez : 06/18/2018<br>carol : 09/09/2016<br>carol : 07/09/2016<br>carol : 3/31/2013<br>ckniffin : 3/26/2013<br>carol : 3/7/2013<br>carol : 3/5/2013<br>ckniffin : 2/28/2013<br>terry : 5/30/2012<br>carol : 5/23/2012<br>terry : 3/27/2012<br>terry : 3/27/2012<br>carol : 7/22/2011<br>carol : 10/26/2010<br>terry : 5/11/2010<br>wwang : 11/6/2009<br>ckniffin : 11/2/2009<br>terry : 3/5/2009<br>wwang : 3/4/2008<br>ckniffin : 2/29/2008<br>wwang : 6/27/2007<br>ckniffin : 6/14/2007<br>wwang : 5/1/2007<br>ckniffin : 4/25/2007<br>alopez : 6/13/2005<br>terry : 4/20/2005<br>terry : 2/10/2005<br>ckniffin : 8/24/2004<br>ckniffin : 4/16/2004<br>carol : 4/1/2004<br>terry : 3/29/2004<br>carol : 2/19/2004<br>terry : 2/19/2004<br>ckniffin : 1/28/2004<br>carol : 1/28/2004<br>ckniffin : 12/29/2003<br>carol : 8/26/2003<br>tkritzer : 8/25/2003<br>tkritzer : 8/22/2003<br>terry : 8/21/2003<br>alopez : 2/13/2002<br>terry : 2/13/2002<br>mcapotos : 2/12/2001<br>mcapotos : 2/8/2001<br>terry : 2/6/2001<br>carol : 1/24/2001<br>terry : 1/23/2001<br>carol : 10/18/1999<br>carol : 10/15/1999<br>carol : 6/1/1999<br>carol : 6/19/1998<br>dholmes : 5/11/1998<br>carol : 4/24/1998<br>mark : 2/18/1998<br>terry : 2/12/1998<br>mark : 11/19/1997<br>jenny : 11/19/1997<br>carol : 6/23/1997<br>mark : 6/16/1997<br>mark : 10/31/1995<br>carol : 10/19/1994<br>davew : 8/19/1994<br>mimadm : 3/29/1994<br>carol : 11/23/1993<br>carol : 12/18/1992
</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