2689 lines
198 KiB
Text
2689 lines
198 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!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
|
|
|
|
- #613280 - HYPERMANGANESEMIA WITH DYSTONIA 1; HMNDYT1
|
|
|
|
|
|
- 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=613280"><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">#613280</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/613280"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS613280"> <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="#inheritance">Inheritance</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="#molecularGenetics">Molecular Genetics</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;">▼</div>
|
|
|
|
<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;">▼</div>
|
|
|
|
<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=HYPERMANGANESEMIA WITH DYSTONIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21405&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK100241/" 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.ncbi.nlm.nih.gov/gtr/all/tests/?term=613280[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309854" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</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;">►</div>
|
|
|
|
<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:0080536" 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/613280" 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://wormbase.org/resources/disease/DOID:0080536" 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>
|
|
|
|
</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.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 702377007<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 309854<br />
|
|
|
|
|
|
<strong>DO:</strong> 0080536<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>
|
|
613280
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HYPERMANGANESEMIA WITH DYSTONIA 1; HMNDYT1
|
|
|
|
</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">
|
|
HYPERMANGANESEMIA WITH DYSTONIA, POLYCYTHEMIA, AND CIRRHOSIS; HMDPC
|
|
</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/1/1714?start=-3&limit=10&highlight=1714">
|
|
1q41
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypermanganesemia with dystonia 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613280"> 613280 </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">
|
|
SLC30A10
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611146"> 611146 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/613280" 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>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS613280" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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/613280" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613280" 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> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
|
|
Liver dysfunction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75183008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75183008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001410" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001410</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001410" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001410</a>]</span><br /> -
|
|
Cirrhosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19943007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19943007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023890&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023890</a>, <a href="https://bioportal.bioontology.org/search?q=C1623038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1623038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</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">
|
|
|
|
- Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
|
|
Hypertonia of the limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838391&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838391</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span><br /> -
|
|
High-steppage gait <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552731&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552731</a>]</span><br /> -
|
|
Fine motor impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228148009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228148009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867864&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867864</a>, <a href="https://bioportal.bioontology.org/search?q=C0556281&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0556281</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007010</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007010</a>]</span><br /> -
|
|
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
|
|
Extrapyramidal signs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43378000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43378000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234133</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span><br /> -
|
|
Parkinsonism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32798002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32798002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G20.C" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G20.C</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001300</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001300</a>]</span><br /> -
|
|
Tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26079004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26079004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span><br /> -
|
|
Bradykinesia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399317006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399317006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0233565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0233565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002067</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002067</a>]</span><br /> -
|
|
Rigidity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700109</a>, <a href="https://bioportal.bioontology.org/search?q=C0026837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span><br /> -
|
|
Postural instability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843921&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843921</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002172" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002172</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002172" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002172</a>]</span><br /> -
|
|
Spastic paraparesis (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312444006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312444006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037771&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037771</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002313</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002313</a>]</span><br /> -
|
|
Brain MRI shows hyperintensities in the basal ganglia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552733&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552733</a>]</span><br /> -
|
|
Lesions in the white matter <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2752009&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2752009</a>]</span><br /> -
|
|
Lesions in the anterior pituitary (less common) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552734&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552734</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sensorimotor neuropathy (1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1112256&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1112256</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007141</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007141</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Polycythemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127062003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127062003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109992005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109992005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D75.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D75.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0032461&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0032461</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001901" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001901</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001901" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001901</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">
|
|
|
|
- Increased serum manganese <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552736&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552736</a>]</span><br /> -
|
|
Hyperbilirubinemia, unconjugated <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7752002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7752002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0268306&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0268306</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008282" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008282</a>]</span><br /> -
|
|
Increased liver enzymes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235996&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235996</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
|
|
Increased erythropoietin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552737&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552737</a>]</span><br /> -
|
|
Low ferritin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0860972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0860972</a>]</span><br /> -
|
|
Low iron <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0860975&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0860975</a>]</span><br /> -
|
|
Increased total iron binding capacity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0854060&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0854060</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025196</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025196</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">
|
|
|
|
- Onset usually in first decade<br /> -
|
|
Adult onset of neurologic symptoms has been reported in 1 family<br /> -
|
|
Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
|
|
Chelation therapy can result in clinical improvement<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 solute carrier family 30 (zinc transporter), member 10 gene (SLC30A10, <a href="/entry/611146#0001">611146.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ 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>
|
|
Hypermanganesemia with dystonia
|
|
- <a href="/phenotypicSeries/PS613280">PS613280</a>
|
|
- 2 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/1/1714?start=-3&limit=10&highlight=1714"> 1q41 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613280"> Hypermanganesemia with dystonia 1 </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/613280"> 613280 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611146"> SLC30A10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611146"> 611146 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/113?start=-3&limit=10&highlight=113"> 8p21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617013"> Hypermanganesemia with dystonia 2 </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/617013"> 617013 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608736"> SLC39A14 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608736"> 608736 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ 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">▼</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 <span class='glyphicon glyphicon-plus-sign'></span> 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 of evidence that hypermanganesemia with dystonia-1 (HMNDYT1) is caused by homozygous mutation in the SLC30A10 gene (<a href="/entry/611146">611146</a>) on chromosome 1q41.</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">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Hypermanganesemia with dystonia-1 (HMNDYT1) is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved (summary by <a href="#6" class="mim-tip-reference" title="Tuschl, K., Clayton, P. T., Gospe, S. M., Jr., Gulab, S., Ibrahim, S., Singhi, P., Aulakh, R., Ribeiro, R. T., Barsottini, O. G., Zaki, M. S., Del Rosario, M. L., Dyack, S., Price, V., Rideout, A., Gordon, K., Wevers, R. A., Kling Chong, W. K., Mills, P. B. <strong>Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.</strong> Am. J. Hum. Genet. 90: 457-466, 2012. Note: Erratum: Am. J. Hum. Genet. 99: 521 only.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341972[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.01.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22341972">Tuschl et al., 2012</a> and <a href="#4" class="mim-tip-reference" title="Quadri, M., Federico, A., Zhao, T., Breedveld, G. J., Battisti, C., Delnooz, C., Severijnen, L.-A., Di Toro Mammarella, L., Mignarri, A., Monti, L., Sanna, A., Lu, P., Punzo, F., Cossu, G., Willemsen, R., Rasi, F., Oostra, B. A., van de Warrenburg, B. P., Bonifati, V. <strong>Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease.</strong> Am. J. Hum. Genet. 90: 467-477, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341971[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.01.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22341971">Quadri et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22341972+22341971" 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 Hypermanganesemia With Dystonia</em></strong></p><p>
|
|
See also HMNDYT2 (<a href="/entry/617013">617013</a>), caused by mutation in the SLC39A14 gene (<a href="/entry/608736">608736</a>) on chromosome 8p21.</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">▼</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><a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a> reported an Arab girl with a constellation of clinical features consisting of hypermanganesemia, liver cirrhosis, an extrapyramidal motor disorder, and polycythemia. She was born to healthy first-cousin parents. The pregnancy, delivery, and neonatal period were uneventful, and her development was normal until the age of 2 years, when difficulty with walking became apparent. This corrected itself until she presented again with walking difficulties at age 11. Her motor problems affected both her gait and fine movements of her hands. Apart from the movement disorder, her general physical health and development were normal for age. At 12 years of age her height and weight were at the 50th percentile, but her head circumference was 50.1 cm (2nd percentile). She showed mild icterus but no stigmata of chronic liver disease; liver and spleen were normal. Neurologic examination showed toe walking, increased tone of all 4 extremities, and dysdiadochokinesis. There was no dysmetria. Ocular examination was normal with no evidence of Kayser-Fleischer rings. She had polycythemia with a hemoglobin of 18 g/dl, unconjugated hyperbilirubinemia, and increased blood manganese concentrations (3,285 nmol/L, normal less than 320 nmol/L). Total iron binding capacity was increased. Plasma copper and zinc levels were normal. Prothrombin time and activated partial thromboplastin time were somewhat prolonged. Liver biopsy showed bridging fibrosis and cirrhosis with patchy moderate to severe portal and periportal chronic inflammatory cell infiltrate. Abdominal ultrasound showed an enlarged liver with coarse echotexture and a mildly enlarged spleen suggestive of cirrhosis and early portal hypertension. Hepatic manganese content was elevated (3.4 microg/g wet weight, normal 1-2 microg/g). Muscle biopsy was microscopically normal, but manganese content was elevated 3-fold. Copper was borderline high in both liver and muscle but not in the range of Wilson disease (<a href="/entry/277900">277900</a>). MRI of the brain showed hyperintense signal from the anterior pituitary, caudate, lentiform, and dentate nuclei and cerebellar white matter in the T1 sequence but normal T2 sequence consistent with manganese deposition in these regions. MRI of the spine was unremarkable. The patient had 4 healthy brothers and 3 healthy sisters; 1 older brother died at the age of 18 years from gastrointestinal hemorrhage secondary to cirrhosis. His clinical course was very similar to that of his sister, including microcephaly and MRI showing manganese deposition in the basal ganglia. <a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a> excluded mutation in the ATP2C2 (<a href="/entry/613082">613082</a>) and ATP2A3 (<a href="/entry/601929">601929</a>) genes as the cause of the disorder in their patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18392750" 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="#2" class="mim-tip-reference" title="Gospe, S. M., Jr., Caruso, R. D., Clegg, M. S., Keen, C. L., Pimstone, N. R., Ducore, J. M., Gettner, S. S., Kreutzer, R. A. <strong>Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis.</strong> Arch. Dis. Child. 83: 439-442, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11040156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11040156</a>] [<a href="https://doi.org/10.1136/adc.83.5.439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11040156">Gospe et al. (2000)</a> reported a 14-year-old white male, the product of a nonconsanguineous union, who presented with stiffness of gait and progressive leg weakness. He had spastic paraparesis of the lower extremities. MRI of the spinal cord was normal but MRI of the brain showed high signal in the lenticular and dentate nuclei, brainstem, and pituitary, consistent with deposition of manganese. Brainstem atrophy was also present. Whole-blood manganese measured 3.48 micromol/l. There was no evidence of environmental exposure. His liver biopsy showed evidence of micronodular cirrhosis with no evidence of steatosis or of increased iron storage. There was no indication of hepatic copper deposition. Liver manganese concentration was approximately 3 times normal. During 11 years of clinical observation, the patient had progressive spastic weakness of the legs leading to loss of ambulation and painful extensor spasms. Whole-blood magnesium ranged from 2.93 to 3.66 micromol/l. The patient had persistent polycythemia, requiring phlebotomy twice weekly. <a href="#3" class="mim-tip-reference" title="Lechpammer, M., Clegg, M. S., Muzar, Z., Heubner, P. A., Jin, L.-W., Gospe, S. M., Jr. <strong>Pathology of inherited manganese transporter deficiency.</strong> Ann. Neurol. 75: 608-612, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24599576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24599576</a>] [<a href="https://doi.org/10.1002/ana.24131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24599576">Lechpammer et al. (2014)</a> reported postmortem examination results on this patient, who died of pneumonia at age 38 years. The liver showed hepatomegaly with micronodular cirrhosis with portal hypertension manifest by congestive splenomegaly and esophageal varices. Many hepatocytes contained a finely granular brown-orange pigment. Western blot analysis showed decreased levels of SLC30A10. Hypertrophic cardiomyopathy was also observed, with granular rhodanine-positive accumulates in rare myocytes. The basal ganglia showed severe neuronal loss in the globus pallidus, and there was deposition of rhodanine-positive brown pigment in residual neurons and astrocytes. Other findings included reactive astrocytosis, myelin loss, and spongiosis. Similar features were observed in the putamen, caudate nucleus, thalamus, and cerebellum. There was diffuse reactive gliosis throughout the white matter with axonal loss in the corticospinal tracts, and the brainstem showed poorly pigmented neurons in the substantia nigra. There were increased levels of Mn and decreased amounts of SLC30A10 in various brain regions. <a href="#3" class="mim-tip-reference" title="Lechpammer, M., Clegg, M. S., Muzar, Z., Heubner, P. A., Jin, L.-W., Gospe, S. M., Jr. <strong>Pathology of inherited manganese transporter deficiency.</strong> Ann. Neurol. 75: 608-612, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24599576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24599576</a>] [<a href="https://doi.org/10.1002/ana.24131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24599576">Lechpammer et al. (2014)</a> noted that this patient had the unusual feature of spastic paraparesis rather than extrapyramidal signs, which may have reflected the corticospinal tract pathology. The findings indicated that SLC30A10 mutations result in chronic, cumulative brain injury, and <a href="#3" class="mim-tip-reference" title="Lechpammer, M., Clegg, M. S., Muzar, Z., Heubner, P. A., Jin, L.-W., Gospe, S. M., Jr. <strong>Pathology of inherited manganese transporter deficiency.</strong> Ann. Neurol. 75: 608-612, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24599576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24599576</a>] [<a href="https://doi.org/10.1002/ana.24131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24599576">Lechpammer et al. (2014)</a> suggested that early chelation therapy may prevent symptom progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24599576+11040156" 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="Sahni, V., Leger, Y., Panaro, L., Allen, M., Giffin, S., Fury, D., Hamm, N. <strong>Case report: a metabolic disorder presenting as pediatric manganism.</strong> Environ. Health Perspect. 115: 1776-1779, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18087599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18087599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18087599[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1289/ehp.10421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18087599">Sahni et al. (2007)</a> and <a href="#1" class="mim-tip-reference" title="Brna, P., Gordon, K., Dooley, J. M., Price, V. <strong>Manganese toxicity in a child with iron deficiency and polycythemia.</strong> J. Child Neurol. 26: 891-894, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596707</a>] [<a href="https://doi.org/10.1177/0883073810393962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596707">Brna et al. (2011)</a> reported a Canadian girl who presented at age 5 years with pica, emotional lability, decreased speech output, echolalia, and social withdrawal. Her motor coordination had deteriorated, and she had lost fine motor skills and was unable to walk independently. Neurologic examination shoed a narrow-based, high stepping gait, mild truncal ataxia, and action tremor. Brain MRI showed hyperintensities in the basal ganglia, and laboratory studies showed increased serum manganese, low iron, and polycythemia. Liver biopsy was normal, but showed increased manganese. Results of extensive environmental studies did not explain the toxicity, suggesting a metabolic disorder. Chelation therapy resulted in some neurologic improvement, as well as improvement of brain lesions. At age 10 years, she had a stable neurologic status and was able to walk short distances, but preferred using a wheelchair. Cognition was unimpaired and she functioned at an appropriate level in school. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18087599+21596707" 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="Tuschl, K., Clayton, P. T., Gospe, S. M., Jr., Gulab, S., Ibrahim, S., Singhi, P., Aulakh, R., Ribeiro, R. T., Barsottini, O. G., Zaki, M. S., Del Rosario, M. L., Dyack, S., Price, V., Rideout, A., Gordon, K., Wevers, R. A., Kling Chong, W. K., Mills, P. B. <strong>Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.</strong> Am. J. Hum. Genet. 90: 457-466, 2012. Note: Erratum: Am. J. Hum. Genet. 99: 521 only.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341972[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.01.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22341972">Tuschl et al. (2012)</a> reported 15 individuals from 8 families with HMNDTY1, including 4 patients from 3 families previously reported by <a href="#2" class="mim-tip-reference" title="Gospe, S. M., Jr., Caruso, R. D., Clegg, M. S., Keen, C. L., Pimstone, N. R., Ducore, J. M., Gettner, S. S., Kreutzer, R. A. <strong>Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis.</strong> Arch. Dis. Child. 83: 439-442, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11040156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11040156</a>] [<a href="https://doi.org/10.1136/adc.83.5.439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11040156">Gospe et al. (2000)</a>, <a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a>, <a href="#5" class="mim-tip-reference" title="Sahni, V., Leger, Y., Panaro, L., Allen, M., Giffin, S., Fury, D., Hamm, N. <strong>Case report: a metabolic disorder presenting as pediatric manganism.</strong> Environ. Health Perspect. 115: 1776-1779, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18087599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18087599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18087599[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1289/ehp.10421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18087599">Sahni et al. (2007)</a>, and <a href="#1" class="mim-tip-reference" title="Brna, P., Gordon, K., Dooley, J. M., Price, V. <strong>Manganese toxicity in a child with iron deficiency and polycythemia.</strong> J. Child Neurol. 26: 891-894, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596707</a>] [<a href="https://doi.org/10.1177/0883073810393962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596707">Brna et al. (2011)</a>. The patients presented between 2 and 15 years of age with gait disturbances and hypertonia, with some becoming wheelchair-bound. Most had a pure 4-limb dystonia, with a high stepping gait and fine motor impairment, sometimes with dysarthria, fine tremor, and bradykinesia; 1 had pure spastic paraparesis without extrapyramidal features. Intellectual development was normal. All had pathognomonic MRI brain scans with hyperintensities of the globus pallidus, putamen, caudate, subthalamic and dentate nucleus and sparing of the thalamus and ventral pons on T1-weighted images. Those with more extensive disease showed white matter and anterior pituitary involvement. Most patients had liver impairment with raised transaminases and unconjugated hyperbilirubinemia; 2 died of cirrhosis. Other features included polycythemia associated with high erythropoietin levels, decreased iron stores, and increased total iron binding capacity. Liver tissue and blood showed significantly increased Mn content, and parental blood Mn levels were mildly increased in 3 families, consistent with a carrier status. Chelation therapy in some patients resulted in improvement of the neurologic symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18087599+21596707+11040156+22341972+18392750" 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="#4" class="mim-tip-reference" title="Quadri, M., Federico, A., Zhao, T., Breedveld, G. J., Battisti, C., Delnooz, C., Severijnen, L.-A., Di Toro Mammarella, L., Mignarri, A., Monti, L., Sanna, A., Lu, P., Punzo, F., Cossu, G., Willemsen, R., Rasi, F., Oostra, B. A., van de Warrenburg, B. P., Bonifati, V. <strong>Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease.</strong> Am. J. Hum. Genet. 90: 467-477, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341971[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.01.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22341971">Quadri et al. (2012)</a> reported 2 consanguineous families, of Italian and Dutch descent, respectively, in which a total of 5 patients had hypermanganesemia associated with degenerative motor symptoms. The patients were adults at the time of the report, ranging in age from 46 to 65 years. In the Italian family, 2 brothers presented at age 47 and 57 years, respectively, with parkinsonism, including gait disturbances, bradykinesia, hypomimia, rigidity, and postural instability. Both also had polycythemia, hepatomegaly, and brain MRI lesions in the basal ganglia, midbrain, thalamus, cerebellum, and corticospinal tract. One patient had a sensorimotor axonal polyneuropathy. Laboratory studies showed markedly increased manganese, increased transferrin, and decreased ferritin. Chelation therapy resulted in clinical improvement. There were 3 affected sibs in the Dutch family. All developed polycythemia in early childhood. Neurologic symptoms appeared at ages 2, 14, and 10 years, respectively, but the features were variable between patients. The oldest brother developed walking difficulties and limb spasms at age 14. This progressed and he developed generalized dystonia and became wheelchair-bound. Brain MRI showed no gross abnormalities. His younger brother developed walking difficulties at age 2 years. He had progressive dystonia and was wheelchair-bound at age 34. Both had increased serum manganese and increased total iron binding capacity, but normal iron. Brain MRI of the older brother was normal, but that of the younger brother showed hyperintense lesions of the globus pallidus. Neither had liver involvement. However, their younger sister died at age 46 of liver cirrhosis, portal hypertension, splenomegaly, and hepatic encephalopathy. She developed gait difficulties at the age of about 10, but there was no clear documentation of dystonia. Manganese levels were never determined, and neuroimaging was never performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22341971" 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">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a> considered autosomal recessive inheritance likely in their patient because the family was consanguineous and the patient and 1 brother were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18392750" 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">▼</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>The patient of <a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a> was treated with co-careldopa with good effect on the dystonia. D-Penicillamine had only modest effect on urinary manganese excretion. However, a 5-day course of disodium calcium edetate at a dose of 1 gram twice daily (20 mg/kg per dose) resulted in a marked increase in 24-hour urinary manganese excretion and a decrease in blood manganese levels to 1,790 by day 4. The patient was started on monthly 5-day courses of chelation therapy, which were well tolerated and led to significant improvement in her dystonia. After 4 years of chelation, the patient's handwriting, tremor, and stiffness were much better; she suffered no obvious progression of her liver disease, although unconjugated hyperbilirubinemia was still present. Repeat liver biopsy showed that chelation therapy had normalized the liver manganese content and there was less inflammation and fibrosis. Blood manganese level was still very high at 2,322 nmol/L. Since manganese intake is virtually impossible to restrict, oral iron therapy was started to act as a competitive inhibitor of manganese absorption. This led to further improvement in patient's motor symptoms and a rapid fall of blood manganese to 171 nmol/L within 1 month. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18392750" 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">▼</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>By homozygosity mapping followed by candidate gene analysis of 2 consanguineous families with HMNDYT1, <a href="#6" class="mim-tip-reference" title="Tuschl, K., Clayton, P. T., Gospe, S. M., Jr., Gulab, S., Ibrahim, S., Singhi, P., Aulakh, R., Ribeiro, R. T., Barsottini, O. G., Zaki, M. S., Del Rosario, M. L., Dyack, S., Price, V., Rideout, A., Gordon, K., Wevers, R. A., Kling Chong, W. K., Mills, P. B. <strong>Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.</strong> Am. J. Hum. Genet. 90: 457-466, 2012. Note: Erratum: Am. J. Hum. Genet. 99: 521 only.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341972[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.01.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22341972">Tuschl et al. (2012)</a> identified a deletion in the SLC30A10 gene (<a href="/entry/611146#0001">611146.0001</a>) in the family reported by <a href="#7" class="mim-tip-reference" title="Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T. <strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong> J. Inherit. Metab. Dis. 31: 151-163, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>] [<a href="https://doi.org/10.1007/s10545-008-0813-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18392750">Tuschl et al. (2008)</a>. The other family had a large deletion encompassing exons 3 and 4 of the SLC30A10 gene. Subsequent mutation analysis in 6 additional families with the disorder identified homozygous mutations in all patients (see, e.g., <a href="/entry/611146#0002">611146.0002</a>-<a href="/entry/611146#0003">611146.0003</a>). Some of the patients had previously been reported (<a href="#2" class="mim-tip-reference" title="Gospe, S. M., Jr., Caruso, R. D., Clegg, M. S., Keen, C. L., Pimstone, N. R., Ducore, J. M., Gettner, S. S., Kreutzer, R. A. <strong>Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis.</strong> Arch. Dis. Child. 83: 439-442, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11040156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11040156</a>] [<a href="https://doi.org/10.1136/adc.83.5.439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11040156">Gospe et al., 2000</a>; <a href="#5" class="mim-tip-reference" title="Sahni, V., Leger, Y., Panaro, L., Allen, M., Giffin, S., Fury, D., Hamm, N. <strong>Case report: a metabolic disorder presenting as pediatric manganism.</strong> Environ. Health Perspect. 115: 1776-1779, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18087599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18087599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18087599[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1289/ehp.10421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18087599">Sahni et al., 2007</a>; <a href="#1" class="mim-tip-reference" title="Brna, P., Gordon, K., Dooley, J. M., Price, V. <strong>Manganese toxicity in a child with iron deficiency and polycythemia.</strong> J. Child Neurol. 26: 891-894, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596707</a>] [<a href="https://doi.org/10.1177/0883073810393962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596707">Brna et al., 2011</a>). When DNA from parents was available, they were found to be heterozygous carriers. In vitro functional expression studies of 2 of the mutant proteins in a yeast strain lacking a manganese transporter demonstrated that both mutant proteins were nonfunctional. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18087599+21596707+11040156+22341972+18392750" 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="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">▼</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="Brna2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brna, P., Gordon, K., Dooley, J. M., Price, V.
|
|
<strong>Manganese toxicity in a child with iron deficiency and polycythemia.</strong>
|
|
J. Child Neurol. 26: 891-894, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21596707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1177/0883073810393962" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Gospe2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gospe, S. M., Jr., Caruso, R. D., Clegg, M. S., Keen, C. L., Pimstone, N. R., Ducore, J. M., Gettner, S. S., Kreutzer, R. A.
|
|
<strong>Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis.</strong>
|
|
Arch. Dis. Child. 83: 439-442, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11040156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11040156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11040156" 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.83.5.439" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Lechpammer2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lechpammer, M., Clegg, M. S., Muzar, Z., Heubner, P. A., Jin, L.-W., Gospe, S. M., Jr.
|
|
<strong>Pathology of inherited manganese transporter deficiency.</strong>
|
|
Ann. Neurol. 75: 608-612, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24599576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24599576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24599576" 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.24131" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Quadri2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quadri, M., Federico, A., Zhao, T., Breedveld, G. J., Battisti, C., Delnooz, C., Severijnen, L.-A., Di Toro Mammarella, L., Mignarri, A., Monti, L., Sanna, A., Lu, P., Punzo, F., Cossu, G., Willemsen, R., Rasi, F., Oostra, B. A., van de Warrenburg, B. P., Bonifati, V.
|
|
<strong>Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease.</strong>
|
|
Am. J. Hum. Genet. 90: 467-477, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341971[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=22341971" 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.ajhg.2012.01.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Sahni2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sahni, V., Leger, Y., Panaro, L., Allen, M., Giffin, S., Fury, D., Hamm, N.
|
|
<strong>Case report: a metabolic disorder presenting as pediatric manganism.</strong>
|
|
Environ. Health Perspect. 115: 1776-1779, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18087599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18087599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18087599[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=18087599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1289/ehp.10421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Tuschl2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tuschl, K., Clayton, P. T., Gospe, S. M., Jr., Gulab, S., Ibrahim, S., Singhi, P., Aulakh, R., Ribeiro, R. T., Barsottini, O. G., Zaki, M. S., Del Rosario, M. L., Dyack, S., Price, V., Rideout, A., Gordon, K., Wevers, R. A., Kling Chong, W. K., Mills, P. B.
|
|
<strong>Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.</strong>
|
|
Am. J. Hum. Genet. 90: 457-466, 2012. Note: Erratum: Am. J. Hum. Genet. 99: 521 only.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22341972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22341972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22341972[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=22341972" 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.ajhg.2012.01.018" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Tuschl2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T.
|
|
<strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong>
|
|
J. Inherit. Metab. Dis. 31: 151-163, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18392750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18392750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18392750" 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/s10545-008-0813-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 8/28/2014
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 3/28/2012
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 2/24/2010
|
|
</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 : 04/17/2023
|
|
</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 : 06/24/2021<br>carol : 03/09/2020<br>carol : 09/14/2016<br>carol : 07/07/2016<br>ckniffin : 6/30/2016<br>carol : 6/20/2016<br>carol : 8/29/2014<br>mcolton : 8/28/2014<br>ckniffin : 8/28/2014<br>carol : 8/28/2014<br>carol : 4/2/2012<br>ckniffin : 3/28/2012<br>alopez : 2/25/2010<br>alopez : 2/25/2010
|
|
</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> 613280
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HYPERMANGANESEMIA WITH DYSTONIA 1; HMNDYT1
|
|
|
|
</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">
|
|
HYPERMANGANESEMIA WITH DYSTONIA, POLYCYTHEMIA, AND CIRRHOSIS; HMDPC
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 702377007;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 309854;
|
|
|
|
|
|
<strong>DO:</strong> 0080536;
|
|
|
|
|
|
</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">
|
|
1q41
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypermanganesemia with dystonia 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613280
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SLC30A10
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
611146
|
|
</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 of evidence that hypermanganesemia with dystonia-1 (HMNDYT1) is caused by homozygous mutation in the SLC30A10 gene (611146) on chromosome 1q41.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hypermanganesemia with dystonia-1 (HMNDYT1) is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved (summary by Tuschl et al., 2012 and Quadri et al., 2012). </p><p><strong><em>Genetic Heterogeneity of Hypermanganesemia With Dystonia</em></strong></p><p>
|
|
See also HMNDYT2 (617013), caused by mutation in the SLC39A14 gene (608736) on chromosome 8p21.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Tuschl et al. (2008) reported an Arab girl with a constellation of clinical features consisting of hypermanganesemia, liver cirrhosis, an extrapyramidal motor disorder, and polycythemia. She was born to healthy first-cousin parents. The pregnancy, delivery, and neonatal period were uneventful, and her development was normal until the age of 2 years, when difficulty with walking became apparent. This corrected itself until she presented again with walking difficulties at age 11. Her motor problems affected both her gait and fine movements of her hands. Apart from the movement disorder, her general physical health and development were normal for age. At 12 years of age her height and weight were at the 50th percentile, but her head circumference was 50.1 cm (2nd percentile). She showed mild icterus but no stigmata of chronic liver disease; liver and spleen were normal. Neurologic examination showed toe walking, increased tone of all 4 extremities, and dysdiadochokinesis. There was no dysmetria. Ocular examination was normal with no evidence of Kayser-Fleischer rings. She had polycythemia with a hemoglobin of 18 g/dl, unconjugated hyperbilirubinemia, and increased blood manganese concentrations (3,285 nmol/L, normal less than 320 nmol/L). Total iron binding capacity was increased. Plasma copper and zinc levels were normal. Prothrombin time and activated partial thromboplastin time were somewhat prolonged. Liver biopsy showed bridging fibrosis and cirrhosis with patchy moderate to severe portal and periportal chronic inflammatory cell infiltrate. Abdominal ultrasound showed an enlarged liver with coarse echotexture and a mildly enlarged spleen suggestive of cirrhosis and early portal hypertension. Hepatic manganese content was elevated (3.4 microg/g wet weight, normal 1-2 microg/g). Muscle biopsy was microscopically normal, but manganese content was elevated 3-fold. Copper was borderline high in both liver and muscle but not in the range of Wilson disease (277900). MRI of the brain showed hyperintense signal from the anterior pituitary, caudate, lentiform, and dentate nuclei and cerebellar white matter in the T1 sequence but normal T2 sequence consistent with manganese deposition in these regions. MRI of the spine was unremarkable. The patient had 4 healthy brothers and 3 healthy sisters; 1 older brother died at the age of 18 years from gastrointestinal hemorrhage secondary to cirrhosis. His clinical course was very similar to that of his sister, including microcephaly and MRI showing manganese deposition in the basal ganglia. Tuschl et al. (2008) excluded mutation in the ATP2C2 (613082) and ATP2A3 (601929) genes as the cause of the disorder in their patient. </p><p>Gospe et al. (2000) reported a 14-year-old white male, the product of a nonconsanguineous union, who presented with stiffness of gait and progressive leg weakness. He had spastic paraparesis of the lower extremities. MRI of the spinal cord was normal but MRI of the brain showed high signal in the lenticular and dentate nuclei, brainstem, and pituitary, consistent with deposition of manganese. Brainstem atrophy was also present. Whole-blood manganese measured 3.48 micromol/l. There was no evidence of environmental exposure. His liver biopsy showed evidence of micronodular cirrhosis with no evidence of steatosis or of increased iron storage. There was no indication of hepatic copper deposition. Liver manganese concentration was approximately 3 times normal. During 11 years of clinical observation, the patient had progressive spastic weakness of the legs leading to loss of ambulation and painful extensor spasms. Whole-blood magnesium ranged from 2.93 to 3.66 micromol/l. The patient had persistent polycythemia, requiring phlebotomy twice weekly. Lechpammer et al. (2014) reported postmortem examination results on this patient, who died of pneumonia at age 38 years. The liver showed hepatomegaly with micronodular cirrhosis with portal hypertension manifest by congestive splenomegaly and esophageal varices. Many hepatocytes contained a finely granular brown-orange pigment. Western blot analysis showed decreased levels of SLC30A10. Hypertrophic cardiomyopathy was also observed, with granular rhodanine-positive accumulates in rare myocytes. The basal ganglia showed severe neuronal loss in the globus pallidus, and there was deposition of rhodanine-positive brown pigment in residual neurons and astrocytes. Other findings included reactive astrocytosis, myelin loss, and spongiosis. Similar features were observed in the putamen, caudate nucleus, thalamus, and cerebellum. There was diffuse reactive gliosis throughout the white matter with axonal loss in the corticospinal tracts, and the brainstem showed poorly pigmented neurons in the substantia nigra. There were increased levels of Mn and decreased amounts of SLC30A10 in various brain regions. Lechpammer et al. (2014) noted that this patient had the unusual feature of spastic paraparesis rather than extrapyramidal signs, which may have reflected the corticospinal tract pathology. The findings indicated that SLC30A10 mutations result in chronic, cumulative brain injury, and Lechpammer et al. (2014) suggested that early chelation therapy may prevent symptom progression. </p><p>Sahni et al. (2007) and Brna et al. (2011) reported a Canadian girl who presented at age 5 years with pica, emotional lability, decreased speech output, echolalia, and social withdrawal. Her motor coordination had deteriorated, and she had lost fine motor skills and was unable to walk independently. Neurologic examination shoed a narrow-based, high stepping gait, mild truncal ataxia, and action tremor. Brain MRI showed hyperintensities in the basal ganglia, and laboratory studies showed increased serum manganese, low iron, and polycythemia. Liver biopsy was normal, but showed increased manganese. Results of extensive environmental studies did not explain the toxicity, suggesting a metabolic disorder. Chelation therapy resulted in some neurologic improvement, as well as improvement of brain lesions. At age 10 years, she had a stable neurologic status and was able to walk short distances, but preferred using a wheelchair. Cognition was unimpaired and she functioned at an appropriate level in school. </p><p>Tuschl et al. (2012) reported 15 individuals from 8 families with HMNDTY1, including 4 patients from 3 families previously reported by Gospe et al. (2000), Tuschl et al. (2008), Sahni et al. (2007), and Brna et al. (2011). The patients presented between 2 and 15 years of age with gait disturbances and hypertonia, with some becoming wheelchair-bound. Most had a pure 4-limb dystonia, with a high stepping gait and fine motor impairment, sometimes with dysarthria, fine tremor, and bradykinesia; 1 had pure spastic paraparesis without extrapyramidal features. Intellectual development was normal. All had pathognomonic MRI brain scans with hyperintensities of the globus pallidus, putamen, caudate, subthalamic and dentate nucleus and sparing of the thalamus and ventral pons on T1-weighted images. Those with more extensive disease showed white matter and anterior pituitary involvement. Most patients had liver impairment with raised transaminases and unconjugated hyperbilirubinemia; 2 died of cirrhosis. Other features included polycythemia associated with high erythropoietin levels, decreased iron stores, and increased total iron binding capacity. Liver tissue and blood showed significantly increased Mn content, and parental blood Mn levels were mildly increased in 3 families, consistent with a carrier status. Chelation therapy in some patients resulted in improvement of the neurologic symptoms. </p><p>Quadri et al. (2012) reported 2 consanguineous families, of Italian and Dutch descent, respectively, in which a total of 5 patients had hypermanganesemia associated with degenerative motor symptoms. The patients were adults at the time of the report, ranging in age from 46 to 65 years. In the Italian family, 2 brothers presented at age 47 and 57 years, respectively, with parkinsonism, including gait disturbances, bradykinesia, hypomimia, rigidity, and postural instability. Both also had polycythemia, hepatomegaly, and brain MRI lesions in the basal ganglia, midbrain, thalamus, cerebellum, and corticospinal tract. One patient had a sensorimotor axonal polyneuropathy. Laboratory studies showed markedly increased manganese, increased transferrin, and decreased ferritin. Chelation therapy resulted in clinical improvement. There were 3 affected sibs in the Dutch family. All developed polycythemia in early childhood. Neurologic symptoms appeared at ages 2, 14, and 10 years, respectively, but the features were variable between patients. The oldest brother developed walking difficulties and limb spasms at age 14. This progressed and he developed generalized dystonia and became wheelchair-bound. Brain MRI showed no gross abnormalities. His younger brother developed walking difficulties at age 2 years. He had progressive dystonia and was wheelchair-bound at age 34. Both had increased serum manganese and increased total iron binding capacity, but normal iron. Brain MRI of the older brother was normal, but that of the younger brother showed hyperintense lesions of the globus pallidus. Neither had liver involvement. However, their younger sister died at age 46 of liver cirrhosis, portal hypertension, splenomegaly, and hepatic encephalopathy. She developed gait difficulties at the age of about 10, but there was no clear documentation of dystonia. Manganese levels were never determined, and neuroimaging was never performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Tuschl et al. (2008) considered autosomal recessive inheritance likely in their patient because the family was consanguineous and the patient and 1 brother were affected. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The patient of Tuschl et al. (2008) was treated with co-careldopa with good effect on the dystonia. D-Penicillamine had only modest effect on urinary manganese excretion. However, a 5-day course of disodium calcium edetate at a dose of 1 gram twice daily (20 mg/kg per dose) resulted in a marked increase in 24-hour urinary manganese excretion and a decrease in blood manganese levels to 1,790 by day 4. The patient was started on monthly 5-day courses of chelation therapy, which were well tolerated and led to significant improvement in her dystonia. After 4 years of chelation, the patient's handwriting, tremor, and stiffness were much better; she suffered no obvious progression of her liver disease, although unconjugated hyperbilirubinemia was still present. Repeat liver biopsy showed that chelation therapy had normalized the liver manganese content and there was less inflammation and fibrosis. Blood manganese level was still very high at 2,322 nmol/L. Since manganese intake is virtually impossible to restrict, oral iron therapy was started to act as a competitive inhibitor of manganese absorption. This led to further improvement in patient's motor symptoms and a rapid fall of blood manganese to 171 nmol/L within 1 month. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By homozygosity mapping followed by candidate gene analysis of 2 consanguineous families with HMNDYT1, Tuschl et al. (2012) identified a deletion in the SLC30A10 gene (611146.0001) in the family reported by Tuschl et al. (2008). The other family had a large deletion encompassing exons 3 and 4 of the SLC30A10 gene. Subsequent mutation analysis in 6 additional families with the disorder identified homozygous mutations in all patients (see, e.g., 611146.0002-611146.0003). Some of the patients had previously been reported (Gospe et al., 2000; Sahni et al., 2007; Brna et al., 2011). When DNA from parents was available, they were found to be heterozygous carriers. In vitro functional expression studies of 2 of the mutant proteins in a yeast strain lacking a manganese transporter demonstrated that both mutant proteins were nonfunctional. </p>
|
|
</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">
|
|
Brna, P., Gordon, K., Dooley, J. M., Price, V.
|
|
<strong>Manganese toxicity in a child with iron deficiency and polycythemia.</strong>
|
|
J. Child Neurol. 26: 891-894, 2011.
|
|
|
|
|
|
[PubMed: 21596707]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1177/0883073810393962]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gospe, S. M., Jr., Caruso, R. D., Clegg, M. S., Keen, C. L., Pimstone, N. R., Ducore, J. M., Gettner, S. S., Kreutzer, R. A.
|
|
<strong>Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis.</strong>
|
|
Arch. Dis. Child. 83: 439-442, 2000.
|
|
|
|
|
|
[PubMed: 11040156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.83.5.439]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lechpammer, M., Clegg, M. S., Muzar, Z., Heubner, P. A., Jin, L.-W., Gospe, S. M., Jr.
|
|
<strong>Pathology of inherited manganese transporter deficiency.</strong>
|
|
Ann. Neurol. 75: 608-612, 2014.
|
|
|
|
|
|
[PubMed: 24599576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.24131]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quadri, M., Federico, A., Zhao, T., Breedveld, G. J., Battisti, C., Delnooz, C., Severijnen, L.-A., Di Toro Mammarella, L., Mignarri, A., Monti, L., Sanna, A., Lu, P., Punzo, F., Cossu, G., Willemsen, R., Rasi, F., Oostra, B. A., van de Warrenburg, B. P., Bonifati, V.
|
|
<strong>Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease.</strong>
|
|
Am. J. Hum. Genet. 90: 467-477, 2012.
|
|
|
|
|
|
[PubMed: 22341971]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.01.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sahni, V., Leger, Y., Panaro, L., Allen, M., Giffin, S., Fury, D., Hamm, N.
|
|
<strong>Case report: a metabolic disorder presenting as pediatric manganism.</strong>
|
|
Environ. Health Perspect. 115: 1776-1779, 2007.
|
|
|
|
|
|
[PubMed: 18087599]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1289/ehp.10421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tuschl, K., Clayton, P. T., Gospe, S. M., Jr., Gulab, S., Ibrahim, S., Singhi, P., Aulakh, R., Ribeiro, R. T., Barsottini, O. G., Zaki, M. S., Del Rosario, M. L., Dyack, S., Price, V., Rideout, A., Gordon, K., Wevers, R. A., Kling Chong, W. K., Mills, P. B.
|
|
<strong>Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.</strong>
|
|
Am. J. Hum. Genet. 90: 457-466, 2012. Note: Erratum: Am. J. Hum. Genet. 99: 521 only.
|
|
|
|
|
|
[PubMed: 22341972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.01.018]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tuschl, K., Mills, P. B., Parsons, H., Malone, M., Fowler, D., Bitner-Glindzicz, M., Clayton, P. T.
|
|
<strong>Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.</strong>
|
|
J. Inherit. Metab. Dis. 31: 151-163, 2008.
|
|
|
|
|
|
[PubMed: 18392750]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10545-008-0813-1]
|
|
|
|
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 8/28/2014<br>Cassandra L. Kniffin - updated : 3/28/2012
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 2/24/2010
|
|
</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 : 04/17/2023<br>carol : 06/24/2021<br>carol : 03/09/2020<br>carol : 09/14/2016<br>carol : 07/07/2016<br>ckniffin : 6/30/2016<br>carol : 6/20/2016<br>carol : 8/29/2014<br>mcolton : 8/28/2014<br>ckniffin : 8/28/2014<br>carol : 8/28/2014<br>carol : 4/2/2012<br>ckniffin : 3/28/2012<br>alopez : 2/25/2010<br>alopez : 2/25/2010
|
|
</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>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</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>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</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">×</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>
|
|
|
|
|