publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/612075

3744 lines
218 KiB
Text
Raw Permalink Blame History

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
<head>
<!--
################################# CRAWLER WARNING #################################
- The terms of service and the robots.txt file disallows crawling of this site,
please see https://omim.org/help/agreement for more information.
- A number of data files are available for download at https://omim.org/downloads.
- We have an API which you can learn about at https://omim.org/help/api and register
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
- You should feel free to contact us at https://omim.org/contact to figure out the best
approach to getting the data you need for your work.
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
DISTRIBUTED CRAWLS OF THIS SITE.
################################# CRAWLER WARNING #################################
-->
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
<meta http-equiv="cache-control" content="no-cache" />
<meta http-equiv="pragma" content="no-cache" />
<meta name="robots" content="index, follow" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
contain copious links to other genetics resources." />
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
<meta name="theme-color" content="#333333" />
<link rel="icon" href="/static/omim/favicon.png" />
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
<link rel="manifest" href="/static/omim/manifest.json" />
<script id='mimBrowserCapability'>
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
</script>
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
<link rel="preconnect" href="https://www.googletagmanager.com" />
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag(){window.dataLayer.push(arguments);}
gtag("js", new Date());
gtag("config", "G-HMPSQC23JJ");
</script>
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
<div id="mimBootstrapDeviceSize">
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
</div>
<title>
Entry
- #612075 - MITOCHONDRIAL DNA DEPLETION SYNDROME 8A (ENCEPHALOMYOPATHIC TYPE WITH RENAL TUBULOPATHY); MTDPS8A
- 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=612075"><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">#612075</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/612075"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="/phenotypicSeries/PS603041"> <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="#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;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">External Links</div>
</div>
</a>
</h4>
</div>
</div>
<div id="mimExternalLinksFold" class="collapse in">
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=MITOCHONDRIAL DNA DEPLETION SYNDROME 8A (ENCEPHALOMYOPATHIC TYPE WITH RENAL TUBULOPATHY)" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</div>
<div id="mimEuroGentestFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19777&Typ=Pat" title="Mitochondrial DNA depletion syndrome, encephalomyopathic form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mitochondrial DNA depletio…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19813&Typ=Pat" title="Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mitochondrial DNA depletio…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=8030&Typ=Pat" title="Mitochondrial neurogastrointestinal encephalomyopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mitochondrial neurogastroi…&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK195854/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/8900" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/rrm2b-related-mitochondrial-dna-depletion-syndrome-encephalomyopathic-form-with-renal-tubulopathy" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=612075[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254803" title="Mitochondrial DNA depletion syndrome, encephalomyopathic form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mitochondrial DNA depletio…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=255235" title="Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mitochondrial DNA depletio…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=298" title="Mitochondrial neurogastrointestinal encephalomyopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mitochondrial neurogastroi…</a></div>
</div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/search?q=DOID:0070331 OR DOID:0080127" 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/612075" 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/search/disease/DOID:0070331 DOID:0080127" 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.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 765100000<br />
<strong>ORPHA:</strong> 254803, 255235, 298<br />
<strong>DO:</strong> 0070331, 0080127<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>
612075
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MITOCHONDRIAL DNA DEPLETION SYNDROME 8A (ENCEPHALOMYOPATHIC TYPE WITH RENAL TUBULOPATHY); MTDPS8A
</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">
MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC, WITH RENAL TUBULOPATHY, AUTOSOMAL RECESSIVE
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
MITOCHONDRIAL DNA DEPLETION SYNDROME 8B (MNGIE TYPE), INCLUDED; MTDPS8B, INCLUDED
</span>
</div>
<div>
<span class="h4 mim-font">
MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, RRM2B-RELATED, INCLUDED<br />
MNGIE, RRM2B-RELATED, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452">
8q22.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy)
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612075"> 612075 </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">
RRM2B
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> 604712 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452">
8q22.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial DNA depletion syndrome 8B (MNGIE type)
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612075"> 612075 </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">
RRM2B
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> 604712 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/612075" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS603041" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/612075" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/612075" 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> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br /> -
Cachexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/238108007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">238108007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/285384003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">285384003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R64" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R64</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006625&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006625</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004326</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004326</a>]</span><br /> -
Weight loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/89362005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">89362005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/816160009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">816160009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/262285001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">262285001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/161832001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">161832001</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3540682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3540682</a>, <a href="https://bioportal.bioontology.org/search?q=C5203233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5203233</a>, <a href="https://bioportal.bioontology.org/search?q=C1262477&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1262477</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001824" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001824</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001824" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001824</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor visual contact <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552514</a>]</span><br /> -
External ophthalmoplegia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19373007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19373007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H49.88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H49.88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/378.55" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">378.55</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162292&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162292</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000544" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000544</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000544" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000544</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Feeding difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br /> -
Intestinal dysmotility (1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552513&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552513</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Proximal renal tubulopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839603&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839603</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000114" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000114</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000114" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000114</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Mitochondrial DNA depletion, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552511&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552511</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237995002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237995002</a>]</span><br /> -
Abnormal mitochondrial proliferation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552512&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552512</a>]</span><br /> -
Cytochrome c oxidase deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/67434000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">67434000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0268237&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0268237</a>]</span><br /> -
Ragged red fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3275417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3275417</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003200" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003200</a>]</span><br />
</span>
</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">
- Neurologic deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Ataxic gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001125&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001125</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</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">
- Aminoaciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35912001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35912001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238621&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238621</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</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 infancy<br /> -
Death can occur in infancy<br /> -
Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
Some patients have later onset and more variable phenotype (MNGIE)<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 ribonucleotide reductase regulatory TP53 inducible subunit M2B gene (RRM2B, <a href="/entry/604712#0001">604712.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Mitochondrial DNA depletion syndrome
- <a href="/phenotypicSeries/PS603041">PS603041</a>
- 25 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/1/1772?start=-3&limit=10&highlight=1772"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/621071"> Mitochondrial DNA depletion syndrome 21 </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/621071"> 621071 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/139270"> GUK1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/139270"> 139270 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/131?start=-3&limit=10&highlight=131"> 2p23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/256810"> Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) </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/256810"> 256810 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/137960"> MPV17 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/137960"> 137960 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/371?start=-3&limit=10&highlight=371"> 2p13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/251880"> Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) </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/251880"> 251880 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601465"> DGUOK </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601465"> 601465 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/413?start=-3&limit=10&highlight=413"> 2p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/245400"> Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) </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/245400"> 245400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611224"> SUCLG1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611224"> 611224 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/975?start=-3&limit=10&highlight=975"> 3q29 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616896"> ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) </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/616896"> 616896 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605290"> OPA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605290"> 605290 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/714?start=-3&limit=10&highlight=714"> 4q35.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615418"> Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR </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/615418"> 615418 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103220"> SLC25A4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103220"> 103220 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/714?start=-3&limit=10&highlight=714"> 4q35.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617184"> Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/617184"> 617184 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103220"> SLC25A4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103220"> 103220 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/722?start=-3&limit=10&highlight=722"> 6q16.1-q16.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615471"> Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) </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/615471"> 615471 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605654"> FBXL4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605654"> 605654 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/21?start=-3&limit=10&highlight=21"> 7p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618567"> Mitochondrial DNA depletion syndrome 17 </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/618567"> 618567 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606906"> MRM2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606906"> 606906 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/744?start=-3&limit=10&highlight=744"> 7q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/212350"> Sengers syndrome </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/212350"> 212350 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610345"> AGK </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610345"> 610345 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452"> 8q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612075"> Mitochondrial DNA depletion syndrome 8B (MNGIE type) </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/612075"> 612075 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> RRM2B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> 604712 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452"> 8q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612075"> Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) </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/612075"> 612075 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> RRM2B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604712"> 604712 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/214?start=-3&limit=10&highlight=214"> 10q21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617156"> ?Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) </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/617156"> 617156 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600438"> TFAM </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600438"> 600438 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/489?start=-3&limit=10&highlight=489"> 10q24.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/271245"> Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) </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/271245"> 271245 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606075"> TWNK </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606075"> 606075 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/158?start=-3&limit=10&highlight=158"> 13q14.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612073"> Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) </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/612073"> 612073 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603921"> SUCLA2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603921"> 603921 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/182?start=-3&limit=10&highlight=182"> 14q13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618811"> ?Mitochondrial DNA depletion syndrome 18 </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/618811"> 618811 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607571"> SLC25A21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607571"> 607571 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/498?start=-3&limit=10&highlight=498"> 15q26.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613662"> Mitochondrial DNA depletion syndrome 4B (MNGIE type) </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/613662"> 613662 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/174763"> POLG </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/174763"> 174763 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/498?start=-3&limit=10&highlight=498"> 15q26.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/203700"> Mitochondrial DNA depletion syndrome 4A (Alpers type) </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/203700"> 203700 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/174763"> POLG </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/174763"> 174763 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/511?start=-3&limit=10&highlight=511"> 16q21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609560"> Mitochondrial DNA depletion syndrome 2 (myopathic type) </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/609560"> 609560 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188250"> TK2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188250"> 188250 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/413?start=-3&limit=10&highlight=413"> 17q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619780"> Mitochondrial DNA depletion syndrome 20 (MNGIE type) </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/619780"> 619780 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600940"> LIG3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600940"> 600940 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/857?start=-3&limit=10&highlight=857"> 17q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619425"> ?Mitochondrial DNA depletion syndrome 16B (neuroophthalmic type) </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/619425"> 619425 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604983"> POLG2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604983"> 604983 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/857?start=-3&limit=10&highlight=857"> 17q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618528"> ?Mitochondrial DNA depletion syndrome 16 (hepatic type) </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/618528"> 618528 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604983"> POLG2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604983"> 604983 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/1040?start=-3&limit=10&highlight=1040"> 17q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618972"> ?Mitochondrial DNA depletion syndrome 19 </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/618972"> 618972 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606794"> SLC25A10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606794"> 606794 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/118?start=-3&limit=10&highlight=118"> 20p11.23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615084"> Mitochondrial DNA depletion syndrome 11 </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/615084"> 615084 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615076"> MGME1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615076"> 615076 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/417?start=-3&limit=10&highlight=417"> 22q13.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603041"> Mitochondrial DNA depletion syndrome 1 (MNGIE type) </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/603041"> 603041 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/131222"> TYMP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/131222"> 131222 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because mitochondrial DNA depletion syndromes 8A (MTDPS8A) and 8B (MTDPS8B) are caused by homozygous or compound heterozygous mutation in the RRM2B gene (<a href="/entry/604712">604712</a>) on chromosome 8q22.</p><p>See also autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA (mtDNA) deletions-5 (PEOA5; <a href="/entry/613077">613077</a>) and rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD; <a href="/entry/268315">268315</a>), allelic disorders caused by heterozygous and homozygous mutations, respectively, in the RRM2B gene.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Mitochondrial DNA depletion syndrome-8A is a severe autosomal recessive disorder characterized by neonatal hypotonia, lactic acidosis, and neurologic deterioration. Renal tubular involvement may also occur (<a href="#1" class="mim-tip-reference" title="Bourdon, A., Minai, L., Serre, V., Jais, J.-P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., Rotig, A. &lt;strong&gt;Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. (Letter)&lt;/strong&gt; Nature Genet. 39: 776-780, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17486094/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17486094&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng2040&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17486094">Bourdon et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17486094" 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>Mitochondrial DNA depletion syndrome-8B is characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes, known as the MNGIE phenotype (<a href="#4" class="mim-tip-reference" title="Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L.-J., Shinawi, M. &lt;strong&gt;Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.&lt;/strong&gt; Arch. Neurol. 66: 1028-1032, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19667227/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19667227&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19667227[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.139&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19667227">Shaibani et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19667227" 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>For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (<a href="/entry/603041">603041</a>).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#1" class="mim-tip-reference" title="Bourdon, A., Minai, L., Serre, V., Jais, J.-P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., Rotig, A. &lt;strong&gt;Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. (Letter)&lt;/strong&gt; Nature Genet. 39: 776-780, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17486094/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17486094&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng2040&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17486094">Bourdon et al. (2007)</a> reported 3 sibs, born of consanguineous Moroccan parents, with severe mtDNA depletion syndrome with less than 1% mtDNA in skeletal muscle. All had neonatal hypotonia, lactic acidosis, and neurologic deterioration with death in the first months of life. One patient developed a proximal renal tubulopathy. Four additional patients from 3 unrelated families had a similar disorder with early death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17486094" 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="Kollberg, G., Darin, N., Benan, K., Moslemi, A.-R., Lindal, S., Tulinius, M., Oldfors, A., Holme, E. &lt;strong&gt;A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.&lt;/strong&gt; Neuromusc. Disord. 19: 147-150, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19138848/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19138848&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.11.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19138848">Kollberg et al. (2009)</a> reported 2 Sudanese brothers, born of consanguineous parents, with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome. The older brother presented at age 2 months with feeding difficulties, failure to thrive, hypotonia, lactic acidosis, and massive aminoaciduria consistent with a renal proximal tubulopathy. He also had poor visual contact and developed seizures. The disorder progressed rapidly, and he died of respiratory insufficiency at the age of 3 months. His younger brother presented at 2 months of age with tonic-clonic seizures. He later had feeding difficulties with failure to thrive, progressive muscle weakness, hypotonia, lactic acidosis, and poor visual contact. He continued to deteriorate and died at 5 months of age. There was no aminoaciduria, but urinary organic acids showed combined keto- and lactic acidosis. Skeletal muscle biopsy of both patients showed cytochrome c oxidase deficiency and pathologic accumulation of fat in many muscle fibers without abnormal mitochondrial proliferation. There was also severe deficiency of mitochondrial respiratory chain complexes. Southern blot analysis of patient cells showed severe mtDNA depletion (1-4% of normal controls). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19138848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Penque, B. A., Su, L., Wang, J., Ji, W., Bale, A., Luh, F., Fulbright, R. K., Fulbright, R. K., Sarmast, U., Sega, A. G., Konstantino, M., Spencer-Manzon, M., Pierce, R., Yen, Y., Lakhani, S. A. &lt;strong&gt;A homozygous variant in RRM2B is associated with severe metabolic acidosis and early neonatal death.&lt;/strong&gt; Europ. J. Med. Genet. 62: 103574, 2019. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30439532/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30439532&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2018.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30439532">Penque et al. (2019)</a> reported a male infant, born of consanguineous Latino parents, who had poor weight gain at 1 month of age and a weak cry and delayed development at 2 months of age. He was found to have elevated ammonia and creatine kinase as well as lactic acidosis, and he was admitted to the hospital. Initial brain MRI was normal. He developed emesis and feeding intolerance, and he was intubated due to labored breathing and hypoxia. Blood cultures grew E. coli. He developed a depressed neurologic status and respiratory failure, and repeat brain MRI with spectroscopy showed restricted diffusion and elevated lactate. The parents elected for palliative care, and he was extubated and died soon after. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30439532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
<a href="#4" class="mim-tip-reference" title="Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L.-J., Shinawi, M. &lt;strong&gt;Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.&lt;/strong&gt; Arch. Neurol. 66: 1028-1032, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19667227/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19667227&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19667227[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.139&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19667227">Shaibani et al. (2009)</a> reported a 42-year-old woman of mixed African American and Latin American descent referred for ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes. At age 30 years, she developed recurrent and severe episodes of nausea and vomiting due to gastrointestinal dysmotility and associated with severe weight loss. She also had gentamicin-induced sensorineural hearing loss. Since age 37, she had progressive restriction of eye movements, ptosis, micronystagmus, dysarthria, unsteady gait, generalized muscle weakness, and areflexia. There was no family history of a similar disorder. Laboratory studies showed mildly increased serum lactate, demyelinating polyneuropathy, increased T2-weighted signals in the basal ganglia, and muscle biopsy with ragged-red fibers and mtDNA depletion (12% of controls). All these findings were consistent with a mitochondrial disorder, although studies of respiratory chain enzymes in skeletal muscle were normal. Genetic analysis identified compound heterozygosity for 2 mutations in the RRM2B gene (R110H, <a href="/entry/604712#0008">604712.0008</a>; R121H, <a href="/entry/604712#0009">604712.0009</a>). <a href="#4" class="mim-tip-reference" title="Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L.-J., Shinawi, M. &lt;strong&gt;Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.&lt;/strong&gt; Arch. Neurol. 66: 1028-1032, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19667227/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19667227&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19667227[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.139&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19667227">Shaibani et al. (2009)</a> noted that this was the oldest reported patient with RRM2B mutations and that her clinical course was different from that reported previously in patients with MNGIE. The findings also broadened the phenotype associated with RRM2B mutations to include an MNGIE (<a href="/entry/603041">603041</a>)-like picture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19667227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In 3 Moroccan sibs with severe autosomal recessive mtDNA depletion syndrome-8A, <a href="#1" class="mim-tip-reference" title="Bourdon, A., Minai, L., Serre, V., Jais, J.-P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., Rotig, A. &lt;strong&gt;Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. (Letter)&lt;/strong&gt; Nature Genet. 39: 776-780, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17486094/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17486094&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng2040&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17486094">Bourdon et al. (2007)</a> identified homozygous or compound heterozygous mutations in the RRM2B gene (<a href="/entry/604712#0001">604712.0001</a>-<a href="/entry/604712#0005">604712.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17486094" 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="Kollberg, G., Darin, N., Benan, K., Moslemi, A.-R., Lindal, S., Tulinius, M., Oldfors, A., Holme, E. &lt;strong&gt;A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.&lt;/strong&gt; Neuromusc. Disord. 19: 147-150, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19138848/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19138848&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.11.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19138848">Kollberg et al. (2009)</a> reported 2 Sudanese brothers, born of consanguineous parents, with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene (G229V; <a href="/entry/604712#0007">604712.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19138848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male infant, born to consanguineous Latino parents, with MTDPS8A, <a href="#3" class="mim-tip-reference" title="Penque, B. A., Su, L., Wang, J., Ji, W., Bale, A., Luh, F., Fulbright, R. K., Fulbright, R. K., Sarmast, U., Sega, A. G., Konstantino, M., Spencer-Manzon, M., Pierce, R., Yen, Y., Lakhani, S. A. &lt;strong&gt;A homozygous variant in RRM2B is associated with severe metabolic acidosis and early neonatal death.&lt;/strong&gt; Europ. J. Med. Genet. 62: 103574, 2019. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30439532/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30439532&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2018.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30439532">Penque et al. (2019)</a> identified a homozygous missense mutation in the RRM2B gene (N221S; <a href="/entry/604712#0015">604712.0015</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Molecular modeling suggested that the mutation disrupts a conserved alpha helix region of the protein by altering intramolecular interactions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30439532" 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">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Bourdon2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bourdon, A., Minai, L., Serre, V., Jais, J.-P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., Rotig, A.
<strong>Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. (Letter)</strong>
Nature Genet. 39: 776-780, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17486094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17486094</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17486094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng2040" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Kollberg2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kollberg, G., Darin, N., Benan, K., Moslemi, A.-R., Lindal, S., Tulinius, M., Oldfors, A., Holme, E.
<strong>A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.</strong>
Neuromusc. Disord. 19: 147-150, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19138848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19138848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19138848" 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.nmd.2008.11.014" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Penque2019" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Penque, B. A., Su, L., Wang, J., Ji, W., Bale, A., Luh, F., Fulbright, R. K., Fulbright, R. K., Sarmast, U., Sega, A. G., Konstantino, M., Spencer-Manzon, M., Pierce, R., Yen, Y., Lakhani, S. A.
<strong>A homozygous variant in RRM2B is associated with severe metabolic acidosis and early neonatal death.</strong>
Europ. J. Med. Genet. 62: 103574, 2019. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30439532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30439532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30439532" 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.ejmg.2018.11.008" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Shaibani2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L.-J., Shinawi, M.
<strong>Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.</strong>
Arch. Neurol. 66: 1028-1032, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19667227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19667227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19667227[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=19667227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneurol.2009.139" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 12/28/2020
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 12/15/2009<br>Cassandra L. Kniffin - updated : 11/3/2009
</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">
Cassandra L. Kniffin : 5/22/2008
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 03/01/2022
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 12/29/2020<br>carol : 12/28/2020<br>carol : 09/07/2018<br>carol : 06/08/2016<br>carol : 10/8/2014<br>tpirozzi : 6/28/2013<br>carol : 12/21/2010<br>ckniffin : 12/20/2010<br>carol : 12/20/2010<br>ckniffin : 12/9/2010<br>carol : 12/23/2009<br>ckniffin : 12/15/2009<br>wwang : 11/19/2009<br>ckniffin : 11/3/2009<br>ckniffin : 11/3/2009<br>ckniffin : 10/13/2009<br>wwang : 5/28/2008<br>ckniffin : 5/22/2008
</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> 612075
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
MITOCHONDRIAL DNA DEPLETION SYNDROME 8A (ENCEPHALOMYOPATHIC TYPE WITH RENAL TUBULOPATHY); MTDPS8A
</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">
MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC, WITH RENAL TUBULOPATHY, AUTOSOMAL RECESSIVE
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
MITOCHONDRIAL DNA DEPLETION SYNDROME 8B (MNGIE TYPE), INCLUDED; MTDPS8B, INCLUDED
</span>
</div>
<div>
<span class="h4 mim-font">
MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, RRM2B-RELATED, INCLUDED<br />
MNGIE, RRM2B-RELATED, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 765100000; &nbsp;
<strong>ORPHA:</strong> 254803, 255235, 298; &nbsp;
<strong>DO:</strong> 0070331, 0080127; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
8q22.3
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy)
</span>
</td>
<td>
<span class="mim-font">
612075
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
RRM2B
</span>
</td>
<td>
<span class="mim-font">
604712
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
8q22.3
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial DNA depletion syndrome 8B (MNGIE type)
</span>
</td>
<td>
<span class="mim-font">
612075
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
RRM2B
</span>
</td>
<td>
<span class="mim-font">
604712
</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 mitochondrial DNA depletion syndromes 8A (MTDPS8A) and 8B (MTDPS8B) are caused by homozygous or compound heterozygous mutation in the RRM2B gene (604712) on chromosome 8q22.</p><p>See also autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA (mtDNA) deletions-5 (PEOA5; 613077) and rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD; 268315), allelic disorders caused by heterozygous and homozygous mutations, respectively, in the RRM2B gene.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Mitochondrial DNA depletion syndrome-8A is a severe autosomal recessive disorder characterized by neonatal hypotonia, lactic acidosis, and neurologic deterioration. Renal tubular involvement may also occur (Bourdon et al., 2007). </p><p>Mitochondrial DNA depletion syndrome-8B is characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes, known as the MNGIE phenotype (Shaibani et al., 2009). </p><p>For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Bourdon et al. (2007) reported 3 sibs, born of consanguineous Moroccan parents, with severe mtDNA depletion syndrome with less than 1% mtDNA in skeletal muscle. All had neonatal hypotonia, lactic acidosis, and neurologic deterioration with death in the first months of life. One patient developed a proximal renal tubulopathy. Four additional patients from 3 unrelated families had a similar disorder with early death. </p><p>Kollberg et al. (2009) reported 2 Sudanese brothers, born of consanguineous parents, with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome. The older brother presented at age 2 months with feeding difficulties, failure to thrive, hypotonia, lactic acidosis, and massive aminoaciduria consistent with a renal proximal tubulopathy. He also had poor visual contact and developed seizures. The disorder progressed rapidly, and he died of respiratory insufficiency at the age of 3 months. His younger brother presented at 2 months of age with tonic-clonic seizures. He later had feeding difficulties with failure to thrive, progressive muscle weakness, hypotonia, lactic acidosis, and poor visual contact. He continued to deteriorate and died at 5 months of age. There was no aminoaciduria, but urinary organic acids showed combined keto- and lactic acidosis. Skeletal muscle biopsy of both patients showed cytochrome c oxidase deficiency and pathologic accumulation of fat in many muscle fibers without abnormal mitochondrial proliferation. There was also severe deficiency of mitochondrial respiratory chain complexes. Southern blot analysis of patient cells showed severe mtDNA depletion (1-4% of normal controls). </p><p>Penque et al. (2019) reported a male infant, born of consanguineous Latino parents, who had poor weight gain at 1 month of age and a weak cry and delayed development at 2 months of age. He was found to have elevated ammonia and creatine kinase as well as lactic acidosis, and he was admitted to the hospital. Initial brain MRI was normal. He developed emesis and feeding intolerance, and he was intubated due to labored breathing and hypoxia. Blood cultures grew E. coli. He developed a depressed neurologic status and respiratory failure, and repeat brain MRI with spectroscopy showed restricted diffusion and elevated lactate. The parents elected for palliative care, and he was extubated and died soon after. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Shaibani et al. (2009) reported a 42-year-old woman of mixed African American and Latin American descent referred for ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes. At age 30 years, she developed recurrent and severe episodes of nausea and vomiting due to gastrointestinal dysmotility and associated with severe weight loss. She also had gentamicin-induced sensorineural hearing loss. Since age 37, she had progressive restriction of eye movements, ptosis, micronystagmus, dysarthria, unsteady gait, generalized muscle weakness, and areflexia. There was no family history of a similar disorder. Laboratory studies showed mildly increased serum lactate, demyelinating polyneuropathy, increased T2-weighted signals in the basal ganglia, and muscle biopsy with ragged-red fibers and mtDNA depletion (12% of controls). All these findings were consistent with a mitochondrial disorder, although studies of respiratory chain enzymes in skeletal muscle were normal. Genetic analysis identified compound heterozygosity for 2 mutations in the RRM2B gene (R110H, 604712.0008; R121H, 604712.0009). Shaibani et al. (2009) noted that this was the oldest reported patient with RRM2B mutations and that her clinical course was different from that reported previously in patients with MNGIE. The findings also broadened the phenotype associated with RRM2B mutations to include an MNGIE (603041)-like picture. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In 3 Moroccan sibs with severe autosomal recessive mtDNA depletion syndrome-8A, Bourdon et al. (2007) identified homozygous or compound heterozygous mutations in the RRM2B gene (604712.0001-604712.0005). </p><p>Kollberg et al. (2009) reported 2 Sudanese brothers, born of consanguineous parents, with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene (G229V; 604712.0007). </p><p>In a male infant, born to consanguineous Latino parents, with MTDPS8A, Penque et al. (2019) identified a homozygous missense mutation in the RRM2B gene (N221S; 604712.0015). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Molecular modeling suggested that the mutation disrupts a conserved alpha helix region of the protein by altering intramolecular interactions. </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">
Bourdon, A., Minai, L., Serre, V., Jais, J.-P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., Rotig, A.
<strong>Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. (Letter)</strong>
Nature Genet. 39: 776-780, 2007.
[PubMed: 17486094]
[Full Text: https://doi.org/10.1038/ng2040]
</p>
</li>
<li>
<p class="mim-text-font">
Kollberg, G., Darin, N., Benan, K., Moslemi, A.-R., Lindal, S., Tulinius, M., Oldfors, A., Holme, E.
<strong>A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.</strong>
Neuromusc. Disord. 19: 147-150, 2009.
[PubMed: 19138848]
[Full Text: https://doi.org/10.1016/j.nmd.2008.11.014]
</p>
</li>
<li>
<p class="mim-text-font">
Penque, B. A., Su, L., Wang, J., Ji, W., Bale, A., Luh, F., Fulbright, R. K., Fulbright, R. K., Sarmast, U., Sega, A. G., Konstantino, M., Spencer-Manzon, M., Pierce, R., Yen, Y., Lakhani, S. A.
<strong>A homozygous variant in RRM2B is associated with severe metabolic acidosis and early neonatal death.</strong>
Europ. J. Med. Genet. 62: 103574, 2019. Note: Electronic Article.
[PubMed: 30439532]
[Full Text: https://doi.org/10.1016/j.ejmg.2018.11.008]
</p>
</li>
<li>
<p class="mim-text-font">
Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L.-J., Shinawi, M.
<strong>Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.</strong>
Arch. Neurol. 66: 1028-1032, 2009.
[PubMed: 19667227]
[Full Text: https://doi.org/10.1001/archneurol.2009.139]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 12/28/2020<br>Cassandra L. Kniffin - updated : 12/15/2009<br>Cassandra L. Kniffin - updated : 11/3/2009
</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">
Cassandra L. Kniffin : 5/22/2008
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 03/01/2022<br>carol : 12/29/2020<br>carol : 12/28/2020<br>carol : 09/07/2018<br>carol : 06/08/2016<br>carol : 10/8/2014<br>tpirozzi : 6/28/2013<br>carol : 12/21/2010<br>ckniffin : 12/20/2010<br>carol : 12/20/2010<br>ckniffin : 12/9/2010<br>carol : 12/23/2009<br>ckniffin : 12/15/2009<br>wwang : 11/19/2009<br>ckniffin : 11/3/2009<br>ckniffin : 11/3/2009<br>ckniffin : 10/13/2009<br>wwang : 5/28/2008<br>ckniffin : 5/22/2008
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
</div>
</div>
</div>
<div class="visible-print-block mim-footer" style="position: relative;">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
<br />
Printed: March 5, 2025
</div>
</div>
</div>
</div>
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
<div class="modal-dialog" role="document">
<div class="modal-content">
<div class="modal-header">
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">&times;</span></button>
<h4 class="modal-title" id="mimDonationPopupModalTitle">
OMIM Donation:
</h4>
</div>
<div class="modal-body">
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Dear OMIM User,
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
To ensure long-term funding for the OMIM project, we have diversified
our revenue stream. We are determined to keep this website freely
accessible. Unfortunately, it is not free to produce. Expert curators
review the literature and organize it to facilitate your work. Over 90%
of the OMIM's operating expenses go to salary support for MD and PhD
science writers and biocurators. Please join your colleagues by making a
donation now and again in the future. Donations are an important
component of our efforts to ensure long-term funding to provide you the
information that you need at your fingertips.
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Thank you in advance for your generous support, <br />
Ada Hamosh, MD, MPH <br />
Scientific Director, OMIM <br />
</p>
</div>
</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
Reference in a new issue View git blame Copy permalink