4231 lines
361 KiB
Text
4231 lines
361 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- #212140 - CARNITINE DEFICIENCY, SYSTEMIC PRIMARY; CDSP
|
|
|
|
|
|
- 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=212140"><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">#212140</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/212140"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=CARNITINE DEFICIENCY, SYSTEMIC PRIMARY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3316&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK84551/" 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/9212" 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/primary-carnitine-deficiency" 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=212140[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
|
|
<div id="mimNewbornScreeningFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Carnitine-Uptake-Defect-ACT-Sheet.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/C0-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=158" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:14365" 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/212140" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:14365" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:212140" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</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> 21764004<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> E71.41<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 277.81<br />
|
|
|
|
|
|
<strong>ORPHA:</strong> 158<br />
|
|
|
|
|
|
<strong>DO:</strong> 14365<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>
|
|
212140
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CARNITINE DEFICIENCY, SYSTEMIC PRIMARY; CDSP
|
|
|
|
</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">
|
|
SYSTEMIC CARNITINE DEFICIENCY; SCD<br />
|
|
CARNITINE DEFICIENCY, SYSTEMIC, DUE TO DEFECT IN RENAL REABSORPTION OF CARNITINE<br />
|
|
CARNITINE DEFICIENCY, PRIMARY<br />
|
|
CARNITINE TRANSPORTER, PLASMA-MEMBRANE, DEFICIENCY OF<br />
|
|
CARNITINE UPTAKE DEFECT; CUD
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/448?start=-3&limit=10&highlight=448">
|
|
5q31.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Carnitine deficiency, systemic primary
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/212140"> 212140 </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">
|
|
SLC22A5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603377"> 603377 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/212140" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<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/212140" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/212140" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cardiomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8186001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8186001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/429.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">429.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018800&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018800</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</a>]</span><br /> -
|
|
Hypertrophic cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195020003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195020003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>, <a href="https://bioportal.bioontology.org/search?q=C0340425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340425</a>, <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span><br /> -
|
|
Congestive heart failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42343007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42343007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/428.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018802</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span><br /> -
|
|
Fatty infiltration of heart muscle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749745</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> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
|
|
Steatosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/442191002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">442191002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187537008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187537008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197321007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29185008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29185008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2711227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2711227</a>, <a href="https://bioportal.bioontology.org/search?q=C0152254&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152254</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</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">
|
|
|
|
- Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br /> -
|
|
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Muscle biopsy shows lipid deposition <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749740&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749740</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">
|
|
|
|
- Lethargy associated with hypoglycemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749736&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749736</a>]</span><br /> -
|
|
Encephalopathy associated with hypoglycemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749737&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749737</a>]</span><br /> -
|
|
Coma associated with hypoglycemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267384006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E15" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E15</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/251.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">251.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001325</a>]</span><br /> -
|
|
Reye syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74351001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74351001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/331.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">331.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035400&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035400</a>]</span><br /> -
|
|
Delay in gross motor development due to weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749739&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749739</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">
|
|
|
|
- Hypoketotic hypoglycemic episodes, acute <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749751&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749751</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">
|
|
|
|
- Abnormal liver enzymes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166643006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166643006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0438237&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0438237</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
|
|
Increased urinary carnitine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749741&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749741</a>]</span><br /> -
|
|
Decreased carnitine in serum, muscle, heart, and liver <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749742&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749742</a>]</span><br /> -
|
|
Impaired carnitine uptake in muscle, heart, kidney, fibroblasts, and lymphocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749743</a>]</span><br /> -
|
|
Hyperammonemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9360008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9360008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E72.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E72.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574662</a>, <a href="https://bioportal.bioontology.org/search?q=C0220994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220994</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span><br /> -
|
|
No dicarboxylic aciduria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850723&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850723</a>]</span><br /> -
|
|
No ketosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749744&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749744</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">
|
|
|
|
- Two main presentations<br /> -
|
|
Onset in infancy of acute hypoglycemic episodes<br /> -
|
|
Onset in childhood (1 to 7 years) of progressive cardiomyopathy and muscle weakness<br /> -
|
|
Carnitine supplementation can prevent further episodes and declines in cardiac function<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the solute carrier family 22 (organic cation transporter), member 5 gene (SLC22A5, <a href="/entry/603377#0001">603377.0001</a>).<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because primary systemic carnitine deficiency (CDSP) is caused by homozygous or compound heterozygous mutation in the SLC22A5 gene (<a href="/entry/603377">603377</a>) on chromosome 5q31.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Primary systemic carnitine deficiency is due to a defect in the high-affinity carnitine transporter expressed in muscle, heart, kidney, lymphoblasts, and fibroblasts. This results in impaired fatty acid oxidation in skeletal and heart muscle. In addition, renal wasting of carnitine results in low serum levels and diminished hepatic uptake of carnitine by passive diffusion, which impairs ketogenesis (<a href="#20" class="mim-tip-reference" title="Lamhonwah, A.-M., Olpin, S. E., Pollitt, R. J., Vianey-Saban, C., Divry, P., Guffon, N., Besley, G. T. N., Onizuka, R., De Meirleir, L. J., Cvitanovic-Sojat, L., Baric, I., Dionisi-Vici, C., Fumic, K., Maradin, M., Tein, I. <strong>Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy.</strong> Am. J. Med. Genet. 111: 271-284, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210323</a>] [<a href="https://doi.org/10.1002/ajmg.10585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210323">Lamhonwah et al., 2002</a>). If diagnosed early, all clinical manifestations of the disorder can be completely reversed by supplementation of carnitine. However, if left untreated, patients will develop lethal heart failure (summary by <a href="#34" class="mim-tip-reference" title="Shibbani, K., Fahed, A. C., Al-Shaar, L., Arabi, M., Nemer, G., Bitar, F., Majdalani, M. <strong>Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype.</strong> Clin. Genet. 85: 127-137, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23379544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23379544</a>] [<a href="https://doi.org/10.1111/cge.12112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23379544">Shibbani et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12210323+23379544" 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>See also myopathic carnitine deficiency (<a href="/entry/212160">212160</a>), which is restricted to skeletal muscle.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Karpati, G., Carpenter, S., Engel, A. G., Watters, G. V., Allen, J., Rothman, S., Klassen, G., Mamer, O. A. <strong>The syndrome of systemic carnitine deficiency: clinical, morphologic, biochemical, and pathophysiologic features.</strong> Neurology 25: 16-24, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/234182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">234182</a>] [<a href="https://doi.org/10.1212/wnl.25.1.16" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="234182">Karpati et al. (1975)</a> reported systemic carnitine deficiency in an 11-year-old boy who had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped muscles. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. There was marked carnitine deficiency in skeletal muscle, plasma, and liver. Oral replacement therapy resulted in clinical improvement and restored carnitine levels to normal in plasma, but not in liver or muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=234182" 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="Chapoy, P. R., Angelini, C., Brown, W. J., Stiff, J. E., Shug, A., Cederbaum, S. D. <strong>Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome.</strong> New Eng. J. Med. 303: 1389-1394, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7432384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7432384</a>] [<a href="https://doi.org/10.1056/NEJM198012113032403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7432384">Chapoy et al. (1980)</a> reported a 3.5-year-old boy who presented at age 3 months with an acute episode of lethargy, somnolence, hypoglycemia, hepatomegaly, and cardiomegaly. He had hypoketotic hypoglycemia associated with decreased carnitine in plasma, muscle, and liver (all less than 5% of normal values). Prolonged treatment with oral carnitine over a 6-month period resulted in increased muscle strength, a dramatic reduction in cardiac size, relief of cardiomyopathy, partial repletion of carnitine levels in plasma and muscle, and complete repletion in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7432384" 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="#39" class="mim-tip-reference" title="Tripp, M. E., Katcher, M. L., Peters, H. A., Gilbert, E. F., Arya, S., Hodach, R. J., Shug, A. L. <strong>Systemic carnitine deficiency presenting as familial endocardial fibroelastosis.</strong> New Eng. J. Med. 305: 385-390, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7254270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7254270</a>] [<a href="https://doi.org/10.1056/NEJM198108133050707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7254270">Tripp et al. (1981)</a> reported systemic carnitine deficiency in a patient with cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7254270" 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="#40" class="mim-tip-reference" title="Waber, L. J., Valle, D., Neill, C., DiMauro, S., Shug, A. <strong>Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.</strong> J. Pediat. 101: 700-705, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7131143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7131143</a>] [<a href="https://doi.org/10.1016/s0022-3476(82)80294-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7131143">Waber et al. (1982)</a> described a 3.5-year-old boy with cardiomegaly, congestive heart failure, and skeletal muscle weakness. A brother had died of heart failure. In the proband, muscle and plasma carnitine were reduced to 2 and 10% of the normal mean values, respectively. Treatment with carnitine resolved the cardiac disease and muscle weakness. Plasma carnitine concentrations increased with treatment, but urinary carnitine excretion also increased 30-fold of normal, indicating a defect in renal carnitine reabsorption. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7131143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Matsuishi, T., Hirata, K., Terasawa, K., Kato, H., Yoshino, M., Ohtaki, E., Hirose, F., Nonaka, I., Sugiyama, N., Ohta, K. <strong>Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy.</strong> Neuropediatrics 16: 6-12, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3974805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3974805</a>] [<a href="https://doi.org/10.1055/s-2008-1052536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3974805">Matsuishi et al. (1985)</a> described 2 Japanese brothers with a lipid storage myopathy and hypertrophic cardiomyopathy. Their developmental milestones were normal until 3 years of age when mild weakness of the lower limbs became evident. Carnitine was decreased in skeletal muscle and serum. Treatment with L-carnitine resulted in marked clinical improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3974805" 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="#38" class="mim-tip-reference" title="Treem, W. R., Stanley, C. A., Finegold, D. N., Hale, D. E., Coates, P. M. <strong>Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts.</strong> New Eng. J. Med. 319: 1331-1336, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185635</a>] [<a href="https://doi.org/10.1056/NEJM198811173192006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3185635">Treem et al. (1988)</a> described a female infant with hypoketotic hypoglycemia who had a serious defect of carnitine transport in kidney, muscle, and cultured fibroblasts. Urinary carnitine content was increased, but plasma content was low. Carnitine concentrations are normally kept 20 to 40 times higher in tissue than in plasma by a carrier-mediated transport process that is driven by the large sodium gradient across the plasma membrane. Carnitine transport systems have been identified that may be involved in the renal conservation of carnitine. Although carnitine deficiency in the liver of this patient could be corrected when plasma carnitine levels were raised to normal, carnitine deficiency in muscle was not corrected, suggesting that a transport defect was present in muscle but not in liver. The same defect may have been present in the patient of <a href="#40" class="mim-tip-reference" title="Waber, L. J., Valle, D., Neill, C., DiMauro, S., Shug, A. <strong>Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.</strong> J. Pediat. 101: 700-705, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7131143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7131143</a>] [<a href="https://doi.org/10.1016/s0022-3476(82)80294-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7131143">Waber et al. (1982)</a>, although the presenting problem in that case was progressive cardiomyopathy and chronic muscle weakness that began at 2 years of age, was not accompanied by episodes of hypoglycemia, and was reversed by carnitine treatment. <a href="#9" class="mim-tip-reference" title="Eriksson, B. O., Lindstedt, S., Nordin, I. <strong>Hereditary defect in carnitine membrane transport is expressed in skin fibroblasts.</strong> Europ. J. Pediat. 147: 662-663, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3181209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3181209</a>] [<a href="https://doi.org/10.1007/BF00442488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3181209">Eriksson et al. (1988)</a> reported very low levels of carnitine in fibroblasts from a girl with carnitine deficiency and myopathy who may have had the same defect as in the patient of <a href="#38" class="mim-tip-reference" title="Treem, W. R., Stanley, C. A., Finegold, D. N., Hale, D. E., Coates, P. M. <strong>Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts.</strong> New Eng. J. Med. 319: 1331-1336, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185635</a>] [<a href="https://doi.org/10.1056/NEJM198811173192006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3185635">Treem et al. (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7131143+3181209+3185635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Stanley, C. A., DeLeeuw, S., Coates, P. M., Vianey-Liaud, C., Divry, P., Bonnefont, J.-P., Saudubray, J.-M., Haymond, M., Trefz, F. K., Breningstall, G. N., Wappner, R. S., Byrd, D. J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S. L., Treem, W. R. <strong>Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake.</strong> Ann. Neurol. 30: 709-716, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1763895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1763895</a>] [<a href="https://doi.org/10.1002/ana.410300512" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1763895">Stanley et al. (1991)</a> examined the presenting features of 15 infants and children with defects in carnitine uptake. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation; the median age of onset was 3 years. Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy became apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes; the defect appeared to be expressed also in muscle and kidney. In parents, the concentrations of plasma carnitine and the rates of carnitine uptake were intermediate between those of affected patients and normal controls, consistent with autosomal recessive inheritance. <a href="#36" class="mim-tip-reference" title="Stanley, C. A., DeLeeuw, S., Coates, P. M., Vianey-Liaud, C., Divry, P., Bonnefont, J.-P., Saudubray, J.-M., Haymond, M., Trefz, F. K., Breningstall, G. N., Wappner, R. S., Byrd, D. J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S. L., Treem, W. R. <strong>Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake.</strong> Ann. Neurol. 30: 709-716, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1763895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1763895</a>] [<a href="https://doi.org/10.1002/ana.410300512" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1763895">Stanley et al. (1991)</a> emphasized that early recognition and treatment with high doses of oral carnitine can be life-saving. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1763895" 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="#35" class="mim-tip-reference" title="Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G. <strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong> Am. J. Hum. Genet. 63: 101-108, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634512</a>] [<a href="https://doi.org/10.1086/301911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634512">Shoji et al. (1998)</a> reported a Japanese girl with carnitine deficiency who began to complain intermittently of easy fatigue, vomiting, and abdominal pain at the age of 7 years and was first admitted to hospital at 8 years of age. She had unexplained fever, weakness, irregular respiration, and bradycardia, and had lapsed into unconsciousness. She was found to have hepatomegaly and muscle weakness. Echocardiogram showed left ventricular hypertrophy with normal left ventricular systolic function. The symptoms gradually abated with intravenous glucose infusion and disappeared within a few days. However, hyperammonemia and extremely low carnitine concentrations in the serum were not alleviated by the treatment. Carnitine uptake was assessed in vitro by use of cultured skin fibroblasts from the proband and her parents. This was the proband's first episode of a Reye-like syndrome. There was no family history of sudden infant death syndrome, Reye syndrome, or unexplained neuralgic, cardiac, or muscle disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Marques, J. S. <strong>Dilated cardiomyopathy caused by plasma membrane carnitine transport defect.</strong> J. Inherit. Metab. Dis. 21: 428-429, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700603</a>] [<a href="https://doi.org/10.1023/a:1005371028370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700603">Marques (1998)</a> reported a 6-year-old Chinese girl, born of nonconsanguineous parents, who presented with acute heart failure due to dilated cardiomyopathy. A defect in the plasma membrane carnitine transporter was confirmed by carnitine uptake assay on fibroblast cultures. She had an excellent response to carnitine therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700603" 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="#27" class="mim-tip-reference" title="Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsujimoto, G., Hayakawa, J., Shimane, M., Tsuji, A. <strong>Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.</strong> Nature Genet. 21: 91-94, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9916797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9916797</a>] [<a href="https://doi.org/10.1038/5030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9916797">Nezu et al. (1999)</a> reported a 5-year-old boy with systemic carnitine deficiency. He had recurrent episodes of Reye syndrome, including encephalopathy, hyperammonemia, elevated liver enzymes, and hepatic steatosis. He had had episodes of hypoglycemia in the first 2 years of life. Oral carnitine prevented further episodes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9916797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Lamhonwah, A.-M., Onizuka, R., Olpin, S. E., Muntoni, F., Tein, I. <strong>OCTN2 mutation (R254X) found in Saudi Arabian kindred: Recurrent mutation or ancient founder mutation?</strong> J. Inherit. Metab. Dis. 27: 473-476, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15303004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15303004</a>] [<a href="https://doi.org/10.1023/B:BOLI.0000037339.25821.87" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15303004">Lamhonwah et al. (2004)</a> reported a 3-year-old Saudi Arabian girl, born of consanguineous parents, who presented at 6 months with recurrent respiratory infections. She had dilated cardiomyopathy, was hypotonic, and showed mildly delayed gross motor development. Laboratory studies showed impaired fatty acid oxidation and decreased carnitine uptake in skin fibroblasts (less than 1% of control values). Treatment with oral carnitine resulted in improved muscle tone and exercise tolerance as well as improved cardiac function. Intellectual and motor development were normal at age 3 years. Molecular analysis identified a homozygous mutation in the SLC22A5 gene (R254X; <a href="/entry/603377#0019">603377.0019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15303004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="El-Hattab, A. W., Li, F.-Y., Shen, J., Powell, B. R., Bawle, E. V., Adams, D. J., Wahl, E., Kobori, J. A., Graham, B., Scaglia, F., Wong, L.-J. <strong>Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.</strong> Genet. Med. 12: 19-24, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20027113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20027113</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c5e6f7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20027113">El-Hattab et al. (2010)</a> identified systemic primary carnitine deficiency in asymptomatic mothers of children with low carnitine detected by newborn screening. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20027113" 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="#34" class="mim-tip-reference" title="Shibbani, K., Fahed, A. C., Al-Shaar, L., Arabi, M., Nemer, G., Bitar, F., Majdalani, M. <strong>Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype.</strong> Clin. Genet. 85: 127-137, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23379544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23379544</a>] [<a href="https://doi.org/10.1111/cge.12112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23379544">Shibbani et al. (2014)</a> reported 8 patients from 5 Lebanese families with primary carnitine deficiency who had an exclusive cardiac phenotype. Two of the families had been reported by <a href="#42" class="mim-tip-reference" title="Yamak, A. A., Bitar, F., Karam, P., Nemer, G. <strong>Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype-phenotype correlation.</strong> Clin. Genet. 72: 59-62, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594400</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00814.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17594400">Yamak et al. (2007)</a>. Seven patients presented with cardiac failure due to cardiomyopathy between ages 8 months and 10 years; an 11-month-old affected twin sib of 1 of the patients had cardiomyopathy but was asymptomatic. A literature review of 61 cases of the disorder, including the 8 Lebanese patients, showed that cardiomyopathy is the most common clinical presentation, with 42.6% of patients having cardiac manifestations only, and 62.3% having cardiac plus other phenotypes. These findings suggested that heart muscle is more susceptible to carnitine deficiency than liver or skeletal muscle, most likely due to its constant need for energy expenditure and dependence on fatty acids. While carnitine levels were associated with type of mutation, there was no correlation between carnitine levels and severity of the phenotype. <a href="#34" class="mim-tip-reference" title="Shibbani, K., Fahed, A. C., Al-Shaar, L., Arabi, M., Nemer, G., Bitar, F., Majdalani, M. <strong>Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype.</strong> Clin. Genet. 85: 127-137, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23379544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23379544</a>] [<a href="https://doi.org/10.1111/cge.12112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23379544">Shibbani et al. (2014)</a> suggested that environmental stress, such as recurrent infection, may also contribute to the disease manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17594400+23379544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The reduction in plasma carnitine levels in the parents of the patients reported by <a href="#40" class="mim-tip-reference" title="Waber, L. J., Valle, D., Neill, C., DiMauro, S., Shug, A. <strong>Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.</strong> J. Pediat. 101: 700-705, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7131143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7131143</a>] [<a href="https://doi.org/10.1016/s0022-3476(82)80294-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7131143">Waber et al. (1982)</a> and <a href="#38" class="mim-tip-reference" title="Treem, W. R., Stanley, C. A., Finegold, D. N., Hale, D. E., Coates, P. M. <strong>Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts.</strong> New Eng. J. Med. 319: 1331-1336, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185635</a>] [<a href="https://doi.org/10.1056/NEJM198811173192006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3185635">Treem et al. (1988)</a> indicated autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7131143+3185635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Eriksson, B. O., Gustafson, B., Lindstedt, S., Nordin, I. <strong>Transport of carnitine into cells in hereditary carnitine deficiency.</strong> J. Inherit. Metab. Dis. 12: 108-111, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2502670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2502670</a>] [<a href="https://doi.org/10.1007/BF01800711" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2502670">Eriksson et al. (1989)</a> showed absence of carrier-dependent uptake of carnitine in fibroblasts from a patient with hereditary carnitine deficiency. The mother and probably the healthy sister had impaired uptake. These findings showed that the defect in this form of carnitine deficiency was an inability to establish a concentration gradient across the cell membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2502670" 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="#37" class="mim-tip-reference" title="Tein, I., De Vivo, D. C., Bierman, F., Pulver, P., De Meirleir, L. J., Cvitanovic-Sojat, L., Pagon, R. A., Bertini, E., Dionisi-Vici, C., Servidei, S., Dimauro, S. <strong>Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.</strong> Pediat. Res. 28: 247-255, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2235122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2235122</a>] [<a href="https://doi.org/10.1203/00006450-199009000-00020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2235122">Tein et al. (1990)</a> also demonstrated impaired uptake of carnitine by skin fibroblasts in childhood carnitine-responsive cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2235122" 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="#12" class="mim-tip-reference" title="Garavaglia, B., Uziel, G., Dworzak, F., Carrara, F., DiDonato, S. <strong>Primary carnitine deficiency: heterozygote and intrafamilial phenotypic variation.</strong> Neurology 41: 1691-1693, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1922823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1922823</a>] [<a href="https://doi.org/10.1212/wnl.41.10.1691" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1922823">Garavaglia et al. (1991)</a> found negligible uptake of carnitine by cultured fibroblasts in 2 affected boys from different families: one had cardiomyopathy and myopathy, and the other had hypoglycemia and myopathy but no cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1922823" 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="#35" class="mim-tip-reference" title="Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G. <strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong> Am. J. Hum. Genet. 63: 101-108, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634512</a>] [<a href="https://doi.org/10.1086/301911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634512">Shoji et al. (1998)</a> studied serum and urinary carnitine levels in a 9-year-old female proband and 26 family members from a Japanese family with primary systemic carnitine deficiency. There were 2 significantly different phenotypes, in terms of serum free-carnitine levels; levels were low (29.5 +/- 5.0 microM) in 14 and normal (46.8 +/- 6.2 microM) in 12. There was no correlation of urinary free-carnitine levels with the low serum-level phenotype (putative heterozygote), but in normal phenotypes (wildtype), urinary levels decreased as the serum levels decreased; renal resorption of free carnitine appeared to be complete in wildtype individuals when the serum free-carnitine level was less than 36 microM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634512" 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>To define the mechanisms producing partially reduced plasma carnitine levels in the parents of patients with primary carnitine deficiency, <a href="#32" class="mim-tip-reference" title="Scaglia, F., Wang, Y., Singh, R. H., Dembure, P. P., Pasquali, M., Fernhoff, P. M., Longo, N. <strong>Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency.</strong> Genet. Med. 1: 34-39, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11261427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11261427</a>] [<a href="https://doi.org/10.1097/00125817-199811000-00008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11261427">Scaglia et al. (1998)</a> examined carnitine transport in vivo and in the fibroblasts of a patient and his heterozygous parents. Fibroblasts from heterozygotes were shown to have a decreased capacity to accumulate carnitine and heterozygotes had increased urinary losses of carnitine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11261427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="diagnosis" class="mim-anchor"></a>
|
|
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#33" class="mim-tip-reference" title="Schimmenti, L. A., Crombez, E. A., Schwahn, B. C., Heese, B. A., Wood, T. C., Schroer, R. J., Bentler, K., Cederbaum, S., Sarafoglou, K., McCann, M., Rinaldo, P., Matern, D., di San Filippo, C. A., Pasquali, M., Berry, S. A., Longo, N. <strong>Expanded newborn screening identifies maternal primary carnitine deficiency.</strong> Molec. Genet. Metab. 90: 441-445, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17126586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17126586</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17126586">Schimmenti et al. (2007)</a> diagnosed primary carnitine deficiency in 6 unrelated women whose unaffected infants were identified with low free carnitine levels by newborn screening using tandem mass spectrometry. The authors concluded that given a lifetime risk of morbidity or sudden death, identification of adult patients with primary carnitine deficiency is an added benefit of expanded newborn screening programs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17126586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In a study of 11 affected individuals with genetically confirmed systemic carnitine deficiency, <a href="#20" class="mim-tip-reference" title="Lamhonwah, A.-M., Olpin, S. E., Pollitt, R. J., Vianey-Saban, C., Divry, P., Guffon, N., Besley, G. T. N., Onizuka, R., De Meirleir, L. J., Cvitanovic-Sojat, L., Baric, I., Dionisi-Vici, C., Fumic, K., Maradin, M., Tein, I. <strong>Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy.</strong> Am. J. Med. Genet. 111: 271-284, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210323</a>] [<a href="https://doi.org/10.1002/ajmg.10585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210323">Lamhonwah et al. (2002)</a> found strong indications that strict compliance with carnitine therapy from birth could prevent the development of the pathologic phenotype, including cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210323" 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="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By linkage analysis in a Japanese family in which 1 individual had systemic carnitine deficiency, <a href="#35" class="mim-tip-reference" title="Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G. <strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong> Am. J. Hum. Genet. 63: 101-108, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634512</a>] [<a href="https://doi.org/10.1086/301911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634512">Shoji et al. (1998)</a> identified a candidate locus, termed SCD, on chromosome 5q. Use of a dominant mode of inheritance for heterozygous family members yielded a 2-point lod score of 4.98 and a multipoint lod score of 5.52 at D5S436. Haplotype analysis revealed that the responsible genetic locus lies between D5S658 and D5S434. The closest microsatellite marker, D5S436, was located at 5q31.1. This region on 5q is syntenic with the murine jvs gene located on chromosome 11 of the mouse. The study indicated the practicality of linkage mapping when only a single clinical case is present, provided that it is possible to convert the trait into a dominant by the identification of heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>After demonstration of a mutation in the Slc22a5 gene in the jvs mouse model of primary systemic carnitine deficiency, <a href="#27" class="mim-tip-reference" title="Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsujimoto, G., Hayakawa, J., Shimane, M., Tsuji, A. <strong>Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.</strong> Nature Genet. 21: 91-94, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9916797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9916797</a>] [<a href="https://doi.org/10.1038/5030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9916797">Nezu et al. (1999)</a> analyzed the human SLC22A5 gene and identified mutations in 3 SCD pedigrees (<a href="/entry/603377#0001">603377.0001</a>-<a href="/entry/603377#0004">603377.0004</a>). Affected individuals in 2 families were homozygous and the affected individual in the third pedigree was a compound heterozygote. Two families had previously been reported by <a href="#25" class="mim-tip-reference" title="Matsuishi, T., Hirata, K., Terasawa, K., Kato, H., Yoshino, M., Ohtaki, E., Hirose, F., Nonaka, I., Sugiyama, N., Ohta, K. <strong>Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy.</strong> Neuropediatrics 16: 6-12, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3974805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3974805</a>] [<a href="https://doi.org/10.1055/s-2008-1052536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3974805">Matsuishi et al. (1985)</a> and <a href="#35" class="mim-tip-reference" title="Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G. <strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong> Am. J. Hum. Genet. 63: 101-108, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634512</a>] [<a href="https://doi.org/10.1086/301911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634512">Shoji et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9916797+9634512+3974805" 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="#22" class="mim-tip-reference" title="Lamhonwah, A.-M., Tein, I. <strong>Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene.</strong> Biochem. Biophys. Res. Commun. 252: 396-401, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9826541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9826541</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9679" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9826541">Lamhonwah and Tein (1998)</a>, who referred to this disorder as carnitine uptake defect (CUD), identified compound heterozygosity for mutations in the gene encoding the OCTN2 transporter (<a href="/entry/603377#0005">603377.0005</a>-<a href="/entry/603377#0007">603377.0007</a>) in 2 patients in whom they had previously documented CUD (<a href="#37" class="mim-tip-reference" title="Tein, I., De Vivo, D. C., Bierman, F., Pulver, P., De Meirleir, L. J., Cvitanovic-Sojat, L., Pagon, R. A., Bertini, E., Dionisi-Vici, C., Servidei, S., Dimauro, S. <strong>Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.</strong> Pediat. Res. 28: 247-255, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2235122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2235122</a>] [<a href="https://doi.org/10.1203/00006450-199009000-00020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2235122">Tein et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2235122+9826541" 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="#41" class="mim-tip-reference" title="Wang, Y., Korman, S. H., Ye, J., Gargus, J. J., Gutman, A., Taroni, F., Garavaglia, B., Longo, N. <strong>Phenotype and genotype variation in primary carnitine deficiency.</strong> Genet. Med. 3: 387-392, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11715001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11715001</a>] [<a href="https://doi.org/10.1097/00125817-200111000-00002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11715001">Wang et al. (2001)</a> reported 4 novel mutations responsible for primary carnitine deficiency. Two patients within the same family who were homozygous for the same mutation (<a href="/entry/603377#0016">603377.0016</a>) had completely different clinical presentations. The first sib presented at 2 years of age in coma during an episode of gastroenteritis, while her older sister had weakness of the proximal limb girdle musculature requiring physical therapy, and developmental delays involving language skills, concentration, and attention span. Starting her on carnitine resulted in marked improvement of muscle tone, general mood, alertness, activity, and concentration span. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11715001" 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="#1" class="mim-tip-reference" title="Amat di San Filippo, C. A., Pasquali, M., Longo, N. <strong>Pharmacological rescue of carnitine transport in primary carnitine deficiency.</strong> Hum. Mutat. 27: 513-523, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16652335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16652335</a>] [<a href="https://doi.org/10.1002/humu.20314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16652335">Amat di San Filippo et al. (2006)</a> found by confocal microscopy that several OCTN2 missense mutants in primary carnitine deficiency matured normally to the plasma membrane. By contrast, other mutations caused significant retention of the mutant OCTN2 transporter in the cytoplasm. Failed maturation to the plasma membrane is a common mechanism in disorders affecting membrane transporters/ion channels, including cystic fibrosis. To correct this defect, <a href="#1" class="mim-tip-reference" title="Amat di San Filippo, C. A., Pasquali, M., Longo, N. <strong>Pharmacological rescue of carnitine transport in primary carnitine deficiency.</strong> Hum. Mutat. 27: 513-523, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16652335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16652335</a>] [<a href="https://doi.org/10.1002/humu.20314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16652335">Amat di San Filippo et al. (2006)</a> tested whether drugs reducing the efficiency of protein degradation in the endoplasmic reticulum (phenylbutyrate, curcumin) or capable of binding the OCTN2 carnitine transporter (verapamil, quinidine) could improve carnitine transport. Prolonged incubation with phenylbutyrate, quinidine, and verapamil partially stimulated carnitine transport, while curcumin was ineffective. The authors concluded that pharmacologic therapy can be effective in partially restoring activity of mutant transporters. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16652335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="El-Hattab, A. W., Li, F.-Y., Shen, J., Powell, B. R., Bawle, E. V., Adams, D. J., Wahl, E., Kobori, J. A., Graham, B., Scaglia, F., Wong, L.-J. <strong>Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.</strong> Genet. Med. 12: 19-24, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20027113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20027113</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c5e6f7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20027113">El-Hattab et al. (2010)</a> reported 5 families in which low free carnitine levels in the infants' newborn screen led to the diagnosis of maternal systemic primary carnitine deficiency. Affected mothers were compound heterozygotes or homozygotes for missense mutations. All infants were asymptomatic at the time of diagnosis and 1 was found to have systemic primary carnitine deficiency. Three mothers were asymptomatic, one had decreased stamina during pregnancy, and the fifth had mild fatigability and developed preeclampsia. <a href="#5" class="mim-tip-reference" title="El-Hattab, A. W., Li, F.-Y., Shen, J., Powell, B. R., Bawle, E. V., Adams, D. J., Wahl, E., Kobori, J. A., Graham, B., Scaglia, F., Wong, L.-J. <strong>Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.</strong> Genet. Med. 12: 19-24, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20027113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20027113</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c5e6f7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20027113">El-Hattab et al. (2010)</a> concluded that these findings provided further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from metabolic decomposition in infancy to an asymptomatic adult. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20027113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#18" class="mim-tip-reference" title="Koizumi, A., Nozaki, J., Ohura, T., Kayo, T., Wada, Y., Nezu, J., Ohashi, R., Tamai, I., Shoji, Y., Takada, G., Kibira, S., Matsuishi, T., Tsuji, A. <strong>Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.</strong> Hum. Molec. Genet. 8: 2247-2254, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545605</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545605">Koizumi et al. (1999)</a> determined serum free-carnitine levels in 973 unrelated white collar workers in Akita, Japan. In 14 of these participants, serum free-carnitine levels were consistently below the 5th percentile. They sequenced the OCTN2 gene in these 14 subjects, as well as in 22 subjects whose carnitine levels were below the 5th percentile in the first screening but were normal in the second measurement, and in 69 individuals with normal carnitine levels for 2 separate measurements. Polymorphic sequences defined 3 major haplotypes with equal frequencies. Mutations were identified in 9 subjects with low carnitine levels. The 2 seemingly frequent mutations were associated with specific haplotypes, suggesting a founder effect. They arrived at a conservative estimate of 1.01% representing the overall prevalence of heterozygotes in the Akita prefecture of Japan, giving an estimated incidence of primary systemic carnitine deficiency as 1 in 40,000 births. Echocardiographic studies of the families of patients with primary carnitine deficiency revealed that the heterozygotes for OCTN2 mutations were predisposed to late-onset benign cardiac hypertrophy (odds ratio 15.1, 95% CI 1.39-164) compared with the wildtypes. Sequencing of DNA isolated from 3 deceased sibs in 2 families retrospectively confirmed that all 3 were homozygous for the OCTN2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#29" class="mim-tip-reference" title="Nyhan, W. L. <strong>Abnormalities of fatty acid oxidation. (Editorial)</strong> New Eng. J. Med. 319: 1344-1346, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185637</a>] [<a href="https://doi.org/10.1056/NEJM198811173192008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3185637">Nyhan (1988)</a> noted that hypoketotic hypoglycemia and secondary carnitine deficiency can be associated with other inherited defects in fatty acid oxidation, in particular MCAD deficiency (<a href="/entry/201450">201450</a>), which is the most common disorder of fatty acid oxidation. In fact, 4 of the most intensively studied patients with presumed systemic carnitine deficiency (<a href="#6" class="mim-tip-reference" title="Engel, A. G., Rebouche, C. J., Wilson, D. M., Glasgow, A. M., Romshe, C. A., Cruse, R. P. <strong>Primary systemic carnitine deficiency. II. Renal handling of carnitine.</strong> Neurology 31: 819-825, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7195503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7195503</a>] [<a href="https://doi.org/10.1212/wnl.31.7.819" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7195503">Engel et al., 1981</a>; <a href="#31" class="mim-tip-reference" title="Rebouche, C. J., Engel, A. G. <strong>Primary systemic carnitine deficiency: I. Carnitine biosynthesis.</strong> Neurology 31: 813-818, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6787460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6787460</a>] [<a href="https://doi.org/10.1212/wnl.31.7.813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6787460">Rebouche and Engel, 1981</a>) were subsequently found to have secondary carnitine deficiency due to MCAD deficiency (<a href="#13" class="mim-tip-reference" title="Hale, D. E., Cruse, R. P., Engel, A. <strong>Familial systemic carnitine deficiency.</strong> Arch. Neurol. 42: 1133, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4062610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4062610</a>] [<a href="https://doi.org/10.1001/archneur.1985.04060110011003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4062610">Hale et al., 1985</a>; <a href="#43" class="mim-tip-reference" title="Zierz, S., Engel, A. G., Romshe, C. A. <strong>Assay of acyl-CoA dehydrogenases in muscle and liver and identification of four new cases of medium-chain acyl-CoA dehydrogenase deficiency associated with systemic carnitine deficiency. (Abstract)</strong> Muscle Nerve 9: 193, 1986."None>Zierz et al., 1986</a>). A feature that distinguishes patients with primary systemic carnitine deficiency from those with enzymatic defects in intramitochondrial beta-oxidation of fatty acids is the very low level of urinary dicarboxylic acids in the former. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4062610+6787460+3185637+7195503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Koizumi, T., Nikaido, H., Hayakawa, J., Nonomura, A., Yoneda, T. <strong>Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2 degree strain of mouse with similarities to Reye's syndrome.</strong> Lab. Anim. 22: 83-87, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352223</a>] [<a href="https://doi.org/10.1258/002367788780746511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3352223">Koizumi et al. (1988)</a> described a spontaneous mutation in the mouse characterized by microvesicular fatty infiltration of viscera, particularly liver and kidney, and death, usually before weaning. The mutation was designated juvenile visceral steatosis (jvs) and was found to be associated with severe systemic carnitine deficiency. Daily administration of L-carnitine started on the tenth day after birth kept the jvs mice alive. <a href="#15" class="mim-tip-reference" title="Horiuchi, M., Kobayashi, K., Yamaguchi, S., Shimizu, N., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T. <strong>Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system.</strong> Biochim. Biophys. Acta 1226: 25-30, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8155735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8155735</a>] [<a href="https://doi.org/10.1016/0925-4439(94)90054-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8155735">Horiuchi et al. (1994)</a> suggested that the primary defect in the jvs mouse is impaired renal transport for carnitine, as had been suggested in human systemic carnitine deficiency. <a href="#28" class="mim-tip-reference" title="Nikaido, H., Horiuchi, M., Hashimoto, N., Saheki, T., Hayakawa, J. <strong>Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic carnitine deficiency in mice, on chromosome 11.</strong> Mammalian Genome 6: 369-370, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626891</a>] [<a href="https://doi.org/10.1007/BF00364804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626891">Nikaido et al. (1995)</a> mapped the jvs gene to mouse chromosome 11. The central part of mouse chromosome 11 is homologous to 5q and 17q in humans. <a href="#30" class="mim-tip-reference" title="Okita, K., Tokino, T., Nishimori, H., Miura, K., Nikaido, H., Hayakawa, J., Ono, A., Kuwajima, M., Matsuzawa, Y., Nakamura, Y. <strong>Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis.</strong> Genomics 33: 289-291, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660978</a>] [<a href="https://doi.org/10.1006/geno.1996.0194" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8660978">Okita et al. (1996)</a> refined the location of the jvs mutation on mouse chromosome 11 as a first step toward positional cloning of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8155735+7626891+8660978+3352223" 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="#16" class="mim-tip-reference" title="Horiuchi, M., Yoshida, H., Kobayashi, K., Kuriwaki, K., Yoshimine, K., Tomomura, M., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T. <strong>Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency.</strong> FEBS Lett. 326: 267-271, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8325377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8325377</a>] [<a href="https://doi.org/10.1016/0014-5793(93)81805-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8325377">Horiuchi et al. (1993)</a> noted that jvs mice treated with L-carnitine before weaning showed cardiac hypertrophy at 3 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8325377" 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>Since the mouse jvs locus was assigned to the region of murine chromosome 11 that is syntenic to human 5q31 where the OCTN2 gene maps, <a href="#23" class="mim-tip-reference" title="Lu, K., Nishimori, H., Nakamura, Y., Shima, K., Kuwajima, M. <strong>A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse.</strong> Biochem. Biophys. Res. Commun. 252: 590-594, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837751</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837751">Lu et al. (1998)</a> isolated the mouse Octn2 gene and screened for mutations in the jvs mouse. They demonstrated a change of codon 352 from CTG (leu) to CGG (arg), located within the sixth transmembrane domain of Octn2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Cederbaum1984" class="mim-tip-reference" title="Cederbaum, S. D., Auestad, N., Bernar, J. <strong>Four-year treatment of systemic carnitine deficiency. (Letter)</strong> New Eng. J. Med. 310: 1395-1396, 1984.">Cederbaum et al. (1984)</a>; <a href="#Cruse1984" class="mim-tip-reference" title="Cruse, R. P., Di Mauro, S., Towfighi, J., Trevisan, C. <strong>Familial systemic carnitine deficiency.</strong> Arch. Neurol. 41: 301-305, 1984.">Cruse et al. (1984)</a>; <a href="#Engel1980" class="mim-tip-reference" title="Engel, A. G. <strong>Possible causes and effects of carnitine deficiency in man. In: Frenkel, R. A.; McGarry, J. D.: Carnitine Biosynthesis, Metabolism and Functions.</strong> New York: Academic Press (pub.) 1980.">Engel (1980)</a>; <a href="#Etzioni1984" class="mim-tip-reference" title="Etzioni, A., Levy, J., Nitzan, M., Erde, P., Benderly, A. <strong>Systemic carnitine deficiency exacerbated by a strict vegetarian diet.</strong> Arch. Dis. Child. 59: 177-179, 1984.">Etzioni
|
|
et al. (1984)</a>; <a href="#Frenkel1980" class="mim-tip-reference" title="Frenkel, R. A., McGarry, J. D. <strong>Carnitine Biosynthesis, Metabolism and Functions.</strong> New York: Academic Press (pub.) 1980.">Frenkel and McGarry (1980)</a>; <a href="#Hart1978" class="mim-tip-reference" title="Hart, Z. H., Chang, C.-H., DiMauro, S., Farooki, Q., Ayyar, R. <strong>Muscle carnitine deficiency and fatal cardiomyopathy.</strong> Neurology 28: 147-151, 1978.">Hart et al. (1978)</a>; <a href="#McGarry1980" class="mim-tip-reference" title="McGarry, J. D., Foster, D. W. <strong>Systemic carnitine deficiency.</strong> New Eng. J. Med. 303: 1413-1415, 1980.">McGarry and Foster (1980)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</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="Amat di San Filippo2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Amat di San Filippo, C. A., Pasquali, M., Longo, N.
|
|
<strong>Pharmacological rescue of carnitine transport in primary carnitine deficiency.</strong>
|
|
Hum. Mutat. 27: 513-523, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16652335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16652335</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16652335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20314" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Cederbaum1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cederbaum, S. D., Auestad, N., Bernar, J.
|
|
<strong>Four-year treatment of systemic carnitine deficiency. (Letter)</strong>
|
|
New Eng. J. Med. 310: 1395-1396, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6717517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6717517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6717517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198405243102121" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Chapoy1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chapoy, P. R., Angelini, C., Brown, W. J., Stiff, J. E., Shug, A., Cederbaum, S. D.
|
|
<strong>Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome.</strong>
|
|
New Eng. J. Med. 303: 1389-1394, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7432384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7432384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7432384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198012113032403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cruse1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cruse, R. P., Di Mauro, S., Towfighi, J., Trevisan, C.
|
|
<strong>Familial systemic carnitine deficiency.</strong>
|
|
Arch. Neurol. 41: 301-305, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6696649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6696649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6696649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1984.04050150079021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="El-Hattab2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
El-Hattab, A. W., Li, F.-Y., Shen, J., Powell, B. R., Bawle, E. V., Adams, D. J., Wahl, E., Kobori, J. A., Graham, B., Scaglia, F., Wong, L.-J.
|
|
<strong>Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.</strong>
|
|
Genet. Med. 12: 19-24, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20027113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20027113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20027113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/GIM.0b013e3181c5e6f7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Engel1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Engel, A. G., Rebouche, C. J., Wilson, D. M., Glasgow, A. M., Romshe, C. A., Cruse, R. P.
|
|
<strong>Primary systemic carnitine deficiency. II. Renal handling of carnitine.</strong>
|
|
Neurology 31: 819-825, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7195503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7195503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7195503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.31.7.819" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Engel1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Engel, A. G.
|
|
<strong>Possible causes and effects of carnitine deficiency in man. In: Frenkel, R. A.; McGarry, J. D.: Carnitine Biosynthesis, Metabolism and Functions.</strong>
|
|
New York: Academic Press (pub.) 1980.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Eriksson1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, B. O., Gustafson, B., Lindstedt, S., Nordin, I.
|
|
<strong>Transport of carnitine into cells in hereditary carnitine deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 12: 108-111, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2502670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2502670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2502670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01800711" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Eriksson1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, B. O., Lindstedt, S., Nordin, I.
|
|
<strong>Hereditary defect in carnitine membrane transport is expressed in skin fibroblasts.</strong>
|
|
Europ. J. Pediat. 147: 662-663, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3181209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3181209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3181209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00442488" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Etzioni1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Etzioni, A., Levy, J., Nitzan, M., Erde, P., Benderly, A.
|
|
<strong>Systemic carnitine deficiency exacerbated by a strict vegetarian diet.</strong>
|
|
Arch. Dis. Child. 59: 177-179, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6703771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6703771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6703771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/adc.59.2.177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Frenkel1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frenkel, R. A., McGarry, J. D.
|
|
<strong>Carnitine Biosynthesis, Metabolism and Functions.</strong>
|
|
New York: Academic Press (pub.) 1980.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Garavaglia1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garavaglia, B., Uziel, G., Dworzak, F., Carrara, F., DiDonato, S.
|
|
<strong>Primary carnitine deficiency: heterozygote and intrafamilial phenotypic variation.</strong>
|
|
Neurology 41: 1691-1693, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1922823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1922823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1922823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.41.10.1691" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hale1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hale, D. E., Cruse, R. P., Engel, A.
|
|
<strong>Familial systemic carnitine deficiency.</strong>
|
|
Arch. Neurol. 42: 1133, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4062610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4062610</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4062610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1985.04060110011003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hart1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hart, Z. H., Chang, C.-H., DiMauro, S., Farooki, Q., Ayyar, R.
|
|
<strong>Muscle carnitine deficiency and fatal cardiomyopathy.</strong>
|
|
Neurology 28: 147-151, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/563997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">563997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=563997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.28.2.147" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Horiuchi1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horiuchi, M., Kobayashi, K., Yamaguchi, S., Shimizu, N., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T.
|
|
<strong>Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system.</strong>
|
|
Biochim. Biophys. Acta 1226: 25-30, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8155735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8155735</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8155735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0925-4439(94)90054-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Horiuchi1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horiuchi, M., Yoshida, H., Kobayashi, K., Kuriwaki, K., Yoshimine, K., Tomomura, M., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T.
|
|
<strong>Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency.</strong>
|
|
FEBS Lett. 326: 267-271, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8325377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8325377</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8325377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0014-5793(93)81805-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Karpati1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Karpati, G., Carpenter, S., Engel, A. G., Watters, G. V., Allen, J., Rothman, S., Klassen, G., Mamer, O. A.
|
|
<strong>The syndrome of systemic carnitine deficiency: clinical, morphologic, biochemical, and pathophysiologic features.</strong>
|
|
Neurology 25: 16-24, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/234182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">234182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=234182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.25.1.16" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Koizumi1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koizumi, A., Nozaki, J., Ohura, T., Kayo, T., Wada, Y., Nezu, J., Ohashi, R., Tamai, I., Shoji, Y., Takada, G., Kibira, S., Matsuishi, T., Tsuji, A.
|
|
<strong>Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.</strong>
|
|
Hum. Molec. Genet. 8: 2247-2254, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545605</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/8.12.2247" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Koizumi1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koizumi, T., Nikaido, H., Hayakawa, J., Nonomura, A., Yoneda, T.
|
|
<strong>Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2 degree strain of mouse with similarities to Reye's syndrome.</strong>
|
|
Lab. Anim. 22: 83-87, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352223</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3352223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1258/002367788780746511" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lamhonwah2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Olpin, S. E., Pollitt, R. J., Vianey-Saban, C., Divry, P., Guffon, N., Besley, G. T. N., Onizuka, R., De Meirleir, L. J., Cvitanovic-Sojat, L., Baric, I., Dionisi-Vici, C., Fumic, K., Maradin, M., Tein, I.
|
|
<strong>Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy.</strong>
|
|
Am. J. Med. Genet. 111: 271-284, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.10585" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Lamhonwah2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Onizuka, R., Olpin, S. E., Muntoni, F., Tein, I.
|
|
<strong>OCTN2 mutation (R254X) found in Saudi Arabian kindred: Recurrent mutation or ancient founder mutation?</strong>
|
|
J. Inherit. Metab. Dis. 27: 473-476, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15303004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15303004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15303004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1023/B:BOLI.0000037339.25821.87" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lamhonwah1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Tein, I.
|
|
<strong>Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 252: 396-401, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9826541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9826541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9826541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1998.9679" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lu, K., Nishimori, H., Nakamura, Y., Shima, K., Kuwajima, M.
|
|
<strong>A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse.</strong>
|
|
Biochem. Biophys. Res. Commun. 252: 590-594, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1998.9708" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Marques1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marques, J. S.
|
|
<strong>Dilated cardiomyopathy caused by plasma membrane carnitine transport defect.</strong>
|
|
J. Inherit. Metab. Dis. 21: 428-429, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1023/a:1005371028370" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Matsuishi1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsuishi, T., Hirata, K., Terasawa, K., Kato, H., Yoshino, M., Ohtaki, E., Hirose, F., Nonaka, I., Sugiyama, N., Ohta, K.
|
|
<strong>Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy.</strong>
|
|
Neuropediatrics 16: 6-12, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3974805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3974805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3974805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1055/s-2008-1052536" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="McGarry1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McGarry, J. D., Foster, D. W.
|
|
<strong>Systemic carnitine deficiency.</strong>
|
|
New Eng. J. Med. 303: 1413-1415, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7432389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7432389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7432389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198012113032410" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Nezu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsujimoto, G., Hayakawa, J., Shimane, M., Tsuji, A.
|
|
<strong>Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.</strong>
|
|
Nature Genet. 21: 91-94, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9916797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9916797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9916797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/5030" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Nikaido1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nikaido, H., Horiuchi, M., Hashimoto, N., Saheki, T., Hayakawa, J.
|
|
<strong>Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic carnitine deficiency in mice, on chromosome 11.</strong>
|
|
Mammalian Genome 6: 369-370, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626891</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00364804" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Nyhan1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nyhan, W. L.
|
|
<strong>Abnormalities of fatty acid oxidation. (Editorial)</strong>
|
|
New Eng. J. Med. 319: 1344-1346, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3185637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198811173192008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Okita1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okita, K., Tokino, T., Nishimori, H., Miura, K., Nikaido, H., Hayakawa, J., Ono, A., Kuwajima, M., Matsuzawa, Y., Nakamura, Y.
|
|
<strong>Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis.</strong>
|
|
Genomics 33: 289-291, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8660978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0194" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Rebouche1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rebouche, C. J., Engel, A. G.
|
|
<strong>Primary systemic carnitine deficiency: I. Carnitine biosynthesis.</strong>
|
|
Neurology 31: 813-818, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6787460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6787460</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6787460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.31.7.813" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Scaglia1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scaglia, F., Wang, Y., Singh, R. H., Dembure, P. P., Pasquali, M., Fernhoff, P. M., Longo, N.
|
|
<strong>Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency.</strong>
|
|
Genet. Med. 1: 34-39, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11261427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11261427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11261427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00125817-199811000-00008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Schimmenti2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schimmenti, L. A., Crombez, E. A., Schwahn, B. C., Heese, B. A., Wood, T. C., Schroer, R. J., Bentler, K., Cederbaum, S., Sarafoglou, K., McCann, M., Rinaldo, P., Matern, D., di San Filippo, C. A., Pasquali, M., Berry, S. A., Longo, N.
|
|
<strong>Expanded newborn screening identifies maternal primary carnitine deficiency.</strong>
|
|
Molec. Genet. Metab. 90: 441-445, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17126586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17126586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17126586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2006.10.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Shibbani2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shibbani, K., Fahed, A. C., Al-Shaar, L., Arabi, M., Nemer, G., Bitar, F., Majdalani, M.
|
|
<strong>Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype.</strong>
|
|
Clin. Genet. 85: 127-137, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23379544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23379544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23379544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/cge.12112" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Shoji1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G.
|
|
<strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong>
|
|
Am. J. Hum. Genet. 63: 101-108, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301911" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Stanley1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stanley, C. A., DeLeeuw, S., Coates, P. M., Vianey-Liaud, C., Divry, P., Bonnefont, J.-P., Saudubray, J.-M., Haymond, M., Trefz, F. K., Breningstall, G. N., Wappner, R. S., Byrd, D. J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S. L., Treem, W. R.
|
|
<strong>Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake.</strong>
|
|
Ann. Neurol. 30: 709-716, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1763895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1763895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1763895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.410300512" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Tein1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tein, I., De Vivo, D. C., Bierman, F., Pulver, P., De Meirleir, L. J., Cvitanovic-Sojat, L., Pagon, R. A., Bertini, E., Dionisi-Vici, C., Servidei, S., Dimauro, S.
|
|
<strong>Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.</strong>
|
|
Pediat. Res. 28: 247-255, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2235122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2235122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2235122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-199009000-00020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Treem1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Treem, W. R., Stanley, C. A., Finegold, D. N., Hale, D. E., Coates, P. M.
|
|
<strong>Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts.</strong>
|
|
New Eng. J. Med. 319: 1331-1336, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3185635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3185635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3185635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198811173192006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Tripp1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tripp, M. E., Katcher, M. L., Peters, H. A., Gilbert, E. F., Arya, S., Hodach, R. J., Shug, A. L.
|
|
<strong>Systemic carnitine deficiency presenting as familial endocardial fibroelastosis.</strong>
|
|
New Eng. J. Med. 305: 385-390, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7254270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7254270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7254270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198108133050707" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Waber1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waber, L. J., Valle, D., Neill, C., DiMauro, S., Shug, A.
|
|
<strong>Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.</strong>
|
|
J. Pediat. 101: 700-705, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7131143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7131143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7131143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-3476(82)80294-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Wang2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, Y., Korman, S. H., Ye, J., Gargus, J. J., Gutman, A., Taroni, F., Garavaglia, B., Longo, N.
|
|
<strong>Phenotype and genotype variation in primary carnitine deficiency.</strong>
|
|
Genet. Med. 3: 387-392, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11715001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11715001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11715001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00125817-200111000-00002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Yamak2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamak, A. A., Bitar, F., Karam, P., Nemer, G.
|
|
<strong>Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype-phenotype correlation.</strong>
|
|
Clin. Genet. 72: 59-62, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17594400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00814.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Zierz1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zierz, S., Engel, A. G., Romshe, C. A.
|
|
<strong>Assay of acyl-CoA dehydrogenases in muscle and liver and identification of four new cases of medium-chain acyl-CoA dehydrogenase deficiency associated with systemic carnitine deficiency. (Abstract)</strong>
|
|
Muscle Nerve 9: 193, 1986.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 6/26/2014
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 5/27/2010<br>Cassandra L. Kniffin - reorganized : 5/15/2009<br>Cassandra L. Kniffin - updated : 5/13/2009<br>Ada Hamosh - updated : 6/14/2007<br>Victor A. McKusick - updated : 9/19/2002<br>Ada Hamosh - updated : 1/9/2002<br>Victor A. McKusick - updated : 11/19/1999<br>Victor A. McKusick - updated : 5/14/1999<br>Victor A. McKusick - updated : 3/11/1999<br>Victor A. McKusick - updated : 2/25/1999<br>Victor A. McKusick - updated : 12/22/1998<br>Victor A. McKusick - updated : 7/17/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/3/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 04/30/2020
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/26/2018<br>carol : 09/09/2016<br>carol : 07/07/2014<br>alopez : 7/1/2014<br>mcolton : 6/30/2014<br>ckniffin : 6/26/2014<br>alopez : 6/2/2010<br>terry : 5/27/2010<br>terry : 8/3/2009<br>carol : 5/15/2009<br>ckniffin : 5/13/2009<br>carol : 9/21/2007<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>alopez : 7/18/2006<br>tkritzer : 9/19/2002<br>tkritzer : 9/19/2002<br>ckniffin : 6/13/2002<br>alopez : 1/17/2002<br>terry : 1/9/2002<br>terry : 2/12/2001<br>alopez : 12/2/1999<br>terry : 11/19/1999<br>mgross : 5/25/1999<br>terry : 5/14/1999<br>carol : 3/24/1999<br>terry : 3/11/1999<br>carol : 3/9/1999<br>terry : 2/25/1999<br>alopez : 1/6/1999<br>alopez : 12/23/1998<br>alopez : 12/22/1998<br>terry : 12/22/1998<br>carol : 7/29/1998<br>carol : 7/21/1998<br>terry : 7/17/1998<br>alopez : 6/10/1997<br>mark : 5/9/1996<br>terry : 5/7/1996<br>terry : 4/30/1996<br>mark : 6/16/1995<br>pfoster : 3/24/1994<br>warfield : 3/8/1994<br>mimadm : 2/19/1994<br>carol : 11/12/1993<br>carol : 7/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 212140
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CARNITINE DEFICIENCY, SYSTEMIC PRIMARY; CDSP
|
|
|
|
</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">
|
|
SYSTEMIC CARNITINE DEFICIENCY; SCD<br />
|
|
CARNITINE DEFICIENCY, SYSTEMIC, DUE TO DEFECT IN RENAL REABSORPTION OF CARNITINE<br />
|
|
CARNITINE DEFICIENCY, PRIMARY<br />
|
|
CARNITINE TRANSPORTER, PLASMA-MEMBRANE, DEFICIENCY OF<br />
|
|
CARNITINE UPTAKE DEFECT; CUD
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 21764004;
|
|
|
|
|
|
<strong>ICD10CM:</strong> E71.41;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 277.81;
|
|
|
|
|
|
<strong>ORPHA:</strong> 158;
|
|
|
|
|
|
<strong>DO:</strong> 14365;
|
|
|
|
|
|
</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">
|
|
5q31.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Carnitine deficiency, systemic primary
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
212140
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SLC22A5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
603377
|
|
</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 primary systemic carnitine deficiency (CDSP) is caused by homozygous or compound heterozygous mutation in the SLC22A5 gene (603377) on chromosome 5q31.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Primary systemic carnitine deficiency is due to a defect in the high-affinity carnitine transporter expressed in muscle, heart, kidney, lymphoblasts, and fibroblasts. This results in impaired fatty acid oxidation in skeletal and heart muscle. In addition, renal wasting of carnitine results in low serum levels and diminished hepatic uptake of carnitine by passive diffusion, which impairs ketogenesis (Lamhonwah et al., 2002). If diagnosed early, all clinical manifestations of the disorder can be completely reversed by supplementation of carnitine. However, if left untreated, patients will develop lethal heart failure (summary by Shibbani et al., 2014). </p><p>See also myopathic carnitine deficiency (212160), which is restricted to skeletal muscle.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Karpati et al. (1975) reported systemic carnitine deficiency in an 11-year-old boy who had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped muscles. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. There was marked carnitine deficiency in skeletal muscle, plasma, and liver. Oral replacement therapy resulted in clinical improvement and restored carnitine levels to normal in plasma, but not in liver or muscle. </p><p>Chapoy et al. (1980) reported a 3.5-year-old boy who presented at age 3 months with an acute episode of lethargy, somnolence, hypoglycemia, hepatomegaly, and cardiomegaly. He had hypoketotic hypoglycemia associated with decreased carnitine in plasma, muscle, and liver (all less than 5% of normal values). Prolonged treatment with oral carnitine over a 6-month period resulted in increased muscle strength, a dramatic reduction in cardiac size, relief of cardiomyopathy, partial repletion of carnitine levels in plasma and muscle, and complete repletion in the liver. </p><p>Tripp et al. (1981) reported systemic carnitine deficiency in a patient with cardiomyopathy. </p><p>Waber et al. (1982) described a 3.5-year-old boy with cardiomegaly, congestive heart failure, and skeletal muscle weakness. A brother had died of heart failure. In the proband, muscle and plasma carnitine were reduced to 2 and 10% of the normal mean values, respectively. Treatment with carnitine resolved the cardiac disease and muscle weakness. Plasma carnitine concentrations increased with treatment, but urinary carnitine excretion also increased 30-fold of normal, indicating a defect in renal carnitine reabsorption. </p><p>Matsuishi et al. (1985) described 2 Japanese brothers with a lipid storage myopathy and hypertrophic cardiomyopathy. Their developmental milestones were normal until 3 years of age when mild weakness of the lower limbs became evident. Carnitine was decreased in skeletal muscle and serum. Treatment with L-carnitine resulted in marked clinical improvement. </p><p>Treem et al. (1988) described a female infant with hypoketotic hypoglycemia who had a serious defect of carnitine transport in kidney, muscle, and cultured fibroblasts. Urinary carnitine content was increased, but plasma content was low. Carnitine concentrations are normally kept 20 to 40 times higher in tissue than in plasma by a carrier-mediated transport process that is driven by the large sodium gradient across the plasma membrane. Carnitine transport systems have been identified that may be involved in the renal conservation of carnitine. Although carnitine deficiency in the liver of this patient could be corrected when plasma carnitine levels were raised to normal, carnitine deficiency in muscle was not corrected, suggesting that a transport defect was present in muscle but not in liver. The same defect may have been present in the patient of Waber et al. (1982), although the presenting problem in that case was progressive cardiomyopathy and chronic muscle weakness that began at 2 years of age, was not accompanied by episodes of hypoglycemia, and was reversed by carnitine treatment. Eriksson et al. (1988) reported very low levels of carnitine in fibroblasts from a girl with carnitine deficiency and myopathy who may have had the same defect as in the patient of Treem et al. (1988). </p><p>Stanley et al. (1991) examined the presenting features of 15 infants and children with defects in carnitine uptake. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation; the median age of onset was 3 years. Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy became apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes; the defect appeared to be expressed also in muscle and kidney. In parents, the concentrations of plasma carnitine and the rates of carnitine uptake were intermediate between those of affected patients and normal controls, consistent with autosomal recessive inheritance. Stanley et al. (1991) emphasized that early recognition and treatment with high doses of oral carnitine can be life-saving. </p><p>Shoji et al. (1998) reported a Japanese girl with carnitine deficiency who began to complain intermittently of easy fatigue, vomiting, and abdominal pain at the age of 7 years and was first admitted to hospital at 8 years of age. She had unexplained fever, weakness, irregular respiration, and bradycardia, and had lapsed into unconsciousness. She was found to have hepatomegaly and muscle weakness. Echocardiogram showed left ventricular hypertrophy with normal left ventricular systolic function. The symptoms gradually abated with intravenous glucose infusion and disappeared within a few days. However, hyperammonemia and extremely low carnitine concentrations in the serum were not alleviated by the treatment. Carnitine uptake was assessed in vitro by use of cultured skin fibroblasts from the proband and her parents. This was the proband's first episode of a Reye-like syndrome. There was no family history of sudden infant death syndrome, Reye syndrome, or unexplained neuralgic, cardiac, or muscle disease. </p><p>Marques (1998) reported a 6-year-old Chinese girl, born of nonconsanguineous parents, who presented with acute heart failure due to dilated cardiomyopathy. A defect in the plasma membrane carnitine transporter was confirmed by carnitine uptake assay on fibroblast cultures. She had an excellent response to carnitine therapy. </p><p>Nezu et al. (1999) reported a 5-year-old boy with systemic carnitine deficiency. He had recurrent episodes of Reye syndrome, including encephalopathy, hyperammonemia, elevated liver enzymes, and hepatic steatosis. He had had episodes of hypoglycemia in the first 2 years of life. Oral carnitine prevented further episodes. </p><p>Lamhonwah et al. (2004) reported a 3-year-old Saudi Arabian girl, born of consanguineous parents, who presented at 6 months with recurrent respiratory infections. She had dilated cardiomyopathy, was hypotonic, and showed mildly delayed gross motor development. Laboratory studies showed impaired fatty acid oxidation and decreased carnitine uptake in skin fibroblasts (less than 1% of control values). Treatment with oral carnitine resulted in improved muscle tone and exercise tolerance as well as improved cardiac function. Intellectual and motor development were normal at age 3 years. Molecular analysis identified a homozygous mutation in the SLC22A5 gene (R254X; 603377.0019). </p><p>El-Hattab et al. (2010) identified systemic primary carnitine deficiency in asymptomatic mothers of children with low carnitine detected by newborn screening. </p><p>Shibbani et al. (2014) reported 8 patients from 5 Lebanese families with primary carnitine deficiency who had an exclusive cardiac phenotype. Two of the families had been reported by Yamak et al. (2007). Seven patients presented with cardiac failure due to cardiomyopathy between ages 8 months and 10 years; an 11-month-old affected twin sib of 1 of the patients had cardiomyopathy but was asymptomatic. A literature review of 61 cases of the disorder, including the 8 Lebanese patients, showed that cardiomyopathy is the most common clinical presentation, with 42.6% of patients having cardiac manifestations only, and 62.3% having cardiac plus other phenotypes. These findings suggested that heart muscle is more susceptible to carnitine deficiency than liver or skeletal muscle, most likely due to its constant need for energy expenditure and dependence on fatty acids. While carnitine levels were associated with type of mutation, there was no correlation between carnitine levels and severity of the phenotype. Shibbani et al. (2014) suggested that environmental stress, such as recurrent infection, may also contribute to the disease manifestations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The reduction in plasma carnitine levels in the parents of the patients reported by Waber et al. (1982) and Treem et al. (1988) indicated autosomal recessive inheritance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Eriksson et al. (1989) showed absence of carrier-dependent uptake of carnitine in fibroblasts from a patient with hereditary carnitine deficiency. The mother and probably the healthy sister had impaired uptake. These findings showed that the defect in this form of carnitine deficiency was an inability to establish a concentration gradient across the cell membrane. </p><p>Tein et al. (1990) also demonstrated impaired uptake of carnitine by skin fibroblasts in childhood carnitine-responsive cardiomyopathy. </p><p>Garavaglia et al. (1991) found negligible uptake of carnitine by cultured fibroblasts in 2 affected boys from different families: one had cardiomyopathy and myopathy, and the other had hypoglycemia and myopathy but no cardiomyopathy. </p><p>Shoji et al. (1998) studied serum and urinary carnitine levels in a 9-year-old female proband and 26 family members from a Japanese family with primary systemic carnitine deficiency. There were 2 significantly different phenotypes, in terms of serum free-carnitine levels; levels were low (29.5 +/- 5.0 microM) in 14 and normal (46.8 +/- 6.2 microM) in 12. There was no correlation of urinary free-carnitine levels with the low serum-level phenotype (putative heterozygote), but in normal phenotypes (wildtype), urinary levels decreased as the serum levels decreased; renal resorption of free carnitine appeared to be complete in wildtype individuals when the serum free-carnitine level was less than 36 microM. </p><p>To define the mechanisms producing partially reduced plasma carnitine levels in the parents of patients with primary carnitine deficiency, Scaglia et al. (1998) examined carnitine transport in vivo and in the fibroblasts of a patient and his heterozygous parents. Fibroblasts from heterozygotes were shown to have a decreased capacity to accumulate carnitine and heterozygotes had increased urinary losses of carnitine. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Schimmenti et al. (2007) diagnosed primary carnitine deficiency in 6 unrelated women whose unaffected infants were identified with low free carnitine levels by newborn screening using tandem mass spectrometry. The authors concluded that given a lifetime risk of morbidity or sudden death, identification of adult patients with primary carnitine deficiency is an added benefit of expanded newborn screening programs. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a study of 11 affected individuals with genetically confirmed systemic carnitine deficiency, Lamhonwah et al. (2002) found strong indications that strict compliance with carnitine therapy from birth could prevent the development of the pathologic phenotype, including cardiomyopathy. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By linkage analysis in a Japanese family in which 1 individual had systemic carnitine deficiency, Shoji et al. (1998) identified a candidate locus, termed SCD, on chromosome 5q. Use of a dominant mode of inheritance for heterozygous family members yielded a 2-point lod score of 4.98 and a multipoint lod score of 5.52 at D5S436. Haplotype analysis revealed that the responsible genetic locus lies between D5S658 and D5S434. The closest microsatellite marker, D5S436, was located at 5q31.1. This region on 5q is syntenic with the murine jvs gene located on chromosome 11 of the mouse. The study indicated the practicality of linkage mapping when only a single clinical case is present, provided that it is possible to convert the trait into a dominant by the identification of heterozygotes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>After demonstration of a mutation in the Slc22a5 gene in the jvs mouse model of primary systemic carnitine deficiency, Nezu et al. (1999) analyzed the human SLC22A5 gene and identified mutations in 3 SCD pedigrees (603377.0001-603377.0004). Affected individuals in 2 families were homozygous and the affected individual in the third pedigree was a compound heterozygote. Two families had previously been reported by Matsuishi et al. (1985) and Shoji et al. (1998). </p><p>Lamhonwah and Tein (1998), who referred to this disorder as carnitine uptake defect (CUD), identified compound heterozygosity for mutations in the gene encoding the OCTN2 transporter (603377.0005-603377.0007) in 2 patients in whom they had previously documented CUD (Tein et al., 1990). </p><p>Wang et al. (2001) reported 4 novel mutations responsible for primary carnitine deficiency. Two patients within the same family who were homozygous for the same mutation (603377.0016) had completely different clinical presentations. The first sib presented at 2 years of age in coma during an episode of gastroenteritis, while her older sister had weakness of the proximal limb girdle musculature requiring physical therapy, and developmental delays involving language skills, concentration, and attention span. Starting her on carnitine resulted in marked improvement of muscle tone, general mood, alertness, activity, and concentration span. </p><p>Amat di San Filippo et al. (2006) found by confocal microscopy that several OCTN2 missense mutants in primary carnitine deficiency matured normally to the plasma membrane. By contrast, other mutations caused significant retention of the mutant OCTN2 transporter in the cytoplasm. Failed maturation to the plasma membrane is a common mechanism in disorders affecting membrane transporters/ion channels, including cystic fibrosis. To correct this defect, Amat di San Filippo et al. (2006) tested whether drugs reducing the efficiency of protein degradation in the endoplasmic reticulum (phenylbutyrate, curcumin) or capable of binding the OCTN2 carnitine transporter (verapamil, quinidine) could improve carnitine transport. Prolonged incubation with phenylbutyrate, quinidine, and verapamil partially stimulated carnitine transport, while curcumin was ineffective. The authors concluded that pharmacologic therapy can be effective in partially restoring activity of mutant transporters. </p><p>El-Hattab et al. (2010) reported 5 families in which low free carnitine levels in the infants' newborn screen led to the diagnosis of maternal systemic primary carnitine deficiency. Affected mothers were compound heterozygotes or homozygotes for missense mutations. All infants were asymptomatic at the time of diagnosis and 1 was found to have systemic primary carnitine deficiency. Three mothers were asymptomatic, one had decreased stamina during pregnancy, and the fifth had mild fatigability and developed preeclampsia. El-Hattab et al. (2010) concluded that these findings provided further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from metabolic decomposition in infancy to an asymptomatic adult. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Koizumi et al. (1999) determined serum free-carnitine levels in 973 unrelated white collar workers in Akita, Japan. In 14 of these participants, serum free-carnitine levels were consistently below the 5th percentile. They sequenced the OCTN2 gene in these 14 subjects, as well as in 22 subjects whose carnitine levels were below the 5th percentile in the first screening but were normal in the second measurement, and in 69 individuals with normal carnitine levels for 2 separate measurements. Polymorphic sequences defined 3 major haplotypes with equal frequencies. Mutations were identified in 9 subjects with low carnitine levels. The 2 seemingly frequent mutations were associated with specific haplotypes, suggesting a founder effect. They arrived at a conservative estimate of 1.01% representing the overall prevalence of heterozygotes in the Akita prefecture of Japan, giving an estimated incidence of primary systemic carnitine deficiency as 1 in 40,000 births. Echocardiographic studies of the families of patients with primary carnitine deficiency revealed that the heterozygotes for OCTN2 mutations were predisposed to late-onset benign cardiac hypertrophy (odds ratio 15.1, 95% CI 1.39-164) compared with the wildtypes. Sequencing of DNA isolated from 3 deceased sibs in 2 families retrospectively confirmed that all 3 were homozygous for the OCTN2 mutations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Nyhan (1988) noted that hypoketotic hypoglycemia and secondary carnitine deficiency can be associated with other inherited defects in fatty acid oxidation, in particular MCAD deficiency (201450), which is the most common disorder of fatty acid oxidation. In fact, 4 of the most intensively studied patients with presumed systemic carnitine deficiency (Engel et al., 1981; Rebouche and Engel, 1981) were subsequently found to have secondary carnitine deficiency due to MCAD deficiency (Hale et al., 1985; Zierz et al., 1986). A feature that distinguishes patients with primary systemic carnitine deficiency from those with enzymatic defects in intramitochondrial beta-oxidation of fatty acids is the very low level of urinary dicarboxylic acids in the former. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Koizumi et al. (1988) described a spontaneous mutation in the mouse characterized by microvesicular fatty infiltration of viscera, particularly liver and kidney, and death, usually before weaning. The mutation was designated juvenile visceral steatosis (jvs) and was found to be associated with severe systemic carnitine deficiency. Daily administration of L-carnitine started on the tenth day after birth kept the jvs mice alive. Horiuchi et al. (1994) suggested that the primary defect in the jvs mouse is impaired renal transport for carnitine, as had been suggested in human systemic carnitine deficiency. Nikaido et al. (1995) mapped the jvs gene to mouse chromosome 11. The central part of mouse chromosome 11 is homologous to 5q and 17q in humans. Okita et al. (1996) refined the location of the jvs mutation on mouse chromosome 11 as a first step toward positional cloning of the gene. </p><p>Horiuchi et al. (1993) noted that jvs mice treated with L-carnitine before weaning showed cardiac hypertrophy at 3 months. </p><p>Since the mouse jvs locus was assigned to the region of murine chromosome 11 that is syntenic to human 5q31 where the OCTN2 gene maps, Lu et al. (1998) isolated the mouse Octn2 gene and screened for mutations in the jvs mouse. They demonstrated a change of codon 352 from CTG (leu) to CGG (arg), located within the sixth transmembrane domain of Octn2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Cederbaum et al. (1984); Cruse et al. (1984); Engel (1980); Etzioni
|
|
et al. (1984); Frenkel and McGarry (1980); Hart et al. (1978);
|
|
McGarry and Foster (1980)
|
|
</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">
|
|
Amat di San Filippo, C. A., Pasquali, M., Longo, N.
|
|
<strong>Pharmacological rescue of carnitine transport in primary carnitine deficiency.</strong>
|
|
Hum. Mutat. 27: 513-523, 2006.
|
|
|
|
|
|
[PubMed: 16652335]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20314]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cederbaum, S. D., Auestad, N., Bernar, J.
|
|
<strong>Four-year treatment of systemic carnitine deficiency. (Letter)</strong>
|
|
New Eng. J. Med. 310: 1395-1396, 1984.
|
|
|
|
|
|
[PubMed: 6717517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198405243102121]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chapoy, P. R., Angelini, C., Brown, W. J., Stiff, J. E., Shug, A., Cederbaum, S. D.
|
|
<strong>Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome.</strong>
|
|
New Eng. J. Med. 303: 1389-1394, 1980.
|
|
|
|
|
|
[PubMed: 7432384]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198012113032403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cruse, R. P., Di Mauro, S., Towfighi, J., Trevisan, C.
|
|
<strong>Familial systemic carnitine deficiency.</strong>
|
|
Arch. Neurol. 41: 301-305, 1984.
|
|
|
|
|
|
[PubMed: 6696649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1984.04050150079021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
El-Hattab, A. W., Li, F.-Y., Shen, J., Powell, B. R., Bawle, E. V., Adams, D. J., Wahl, E., Kobori, J. A., Graham, B., Scaglia, F., Wong, L.-J.
|
|
<strong>Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.</strong>
|
|
Genet. Med. 12: 19-24, 2010.
|
|
|
|
|
|
[PubMed: 20027113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/GIM.0b013e3181c5e6f7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Engel, A. G., Rebouche, C. J., Wilson, D. M., Glasgow, A. M., Romshe, C. A., Cruse, R. P.
|
|
<strong>Primary systemic carnitine deficiency. II. Renal handling of carnitine.</strong>
|
|
Neurology 31: 819-825, 1981.
|
|
|
|
|
|
[PubMed: 7195503]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.31.7.819]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Engel, A. G.
|
|
<strong>Possible causes and effects of carnitine deficiency in man. In: Frenkel, R. A.; McGarry, J. D.: Carnitine Biosynthesis, Metabolism and Functions.</strong>
|
|
New York: Academic Press (pub.) 1980.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksson, B. O., Gustafson, B., Lindstedt, S., Nordin, I.
|
|
<strong>Transport of carnitine into cells in hereditary carnitine deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 12: 108-111, 1989.
|
|
|
|
|
|
[PubMed: 2502670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01800711]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksson, B. O., Lindstedt, S., Nordin, I.
|
|
<strong>Hereditary defect in carnitine membrane transport is expressed in skin fibroblasts.</strong>
|
|
Europ. J. Pediat. 147: 662-663, 1988.
|
|
|
|
|
|
[PubMed: 3181209]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00442488]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Etzioni, A., Levy, J., Nitzan, M., Erde, P., Benderly, A.
|
|
<strong>Systemic carnitine deficiency exacerbated by a strict vegetarian diet.</strong>
|
|
Arch. Dis. Child. 59: 177-179, 1984.
|
|
|
|
|
|
[PubMed: 6703771]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.59.2.177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frenkel, R. A., McGarry, J. D.
|
|
<strong>Carnitine Biosynthesis, Metabolism and Functions.</strong>
|
|
New York: Academic Press (pub.) 1980.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garavaglia, B., Uziel, G., Dworzak, F., Carrara, F., DiDonato, S.
|
|
<strong>Primary carnitine deficiency: heterozygote and intrafamilial phenotypic variation.</strong>
|
|
Neurology 41: 1691-1693, 1991.
|
|
|
|
|
|
[PubMed: 1922823]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.41.10.1691]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hale, D. E., Cruse, R. P., Engel, A.
|
|
<strong>Familial systemic carnitine deficiency.</strong>
|
|
Arch. Neurol. 42: 1133, 1985.
|
|
|
|
|
|
[PubMed: 4062610]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1985.04060110011003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hart, Z. H., Chang, C.-H., DiMauro, S., Farooki, Q., Ayyar, R.
|
|
<strong>Muscle carnitine deficiency and fatal cardiomyopathy.</strong>
|
|
Neurology 28: 147-151, 1978.
|
|
|
|
|
|
[PubMed: 563997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.28.2.147]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horiuchi, M., Kobayashi, K., Yamaguchi, S., Shimizu, N., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T.
|
|
<strong>Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system.</strong>
|
|
Biochim. Biophys. Acta 1226: 25-30, 1994.
|
|
|
|
|
|
[PubMed: 8155735]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0925-4439(94)90054-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horiuchi, M., Yoshida, H., Kobayashi, K., Kuriwaki, K., Yoshimine, K., Tomomura, M., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M., Saheki, T.
|
|
<strong>Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency.</strong>
|
|
FEBS Lett. 326: 267-271, 1993.
|
|
|
|
|
|
[PubMed: 8325377]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(93)81805-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karpati, G., Carpenter, S., Engel, A. G., Watters, G. V., Allen, J., Rothman, S., Klassen, G., Mamer, O. A.
|
|
<strong>The syndrome of systemic carnitine deficiency: clinical, morphologic, biochemical, and pathophysiologic features.</strong>
|
|
Neurology 25: 16-24, 1975.
|
|
|
|
|
|
[PubMed: 234182]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.25.1.16]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koizumi, A., Nozaki, J., Ohura, T., Kayo, T., Wada, Y., Nezu, J., Ohashi, R., Tamai, I., Shoji, Y., Takada, G., Kibira, S., Matsuishi, T., Tsuji, A.
|
|
<strong>Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.</strong>
|
|
Hum. Molec. Genet. 8: 2247-2254, 1999.
|
|
|
|
|
|
[PubMed: 10545605]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.12.2247]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koizumi, T., Nikaido, H., Hayakawa, J., Nonomura, A., Yoneda, T.
|
|
<strong>Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2 degree strain of mouse with similarities to Reye's syndrome.</strong>
|
|
Lab. Anim. 22: 83-87, 1988.
|
|
|
|
|
|
[PubMed: 3352223]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1258/002367788780746511]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Olpin, S. E., Pollitt, R. J., Vianey-Saban, C., Divry, P., Guffon, N., Besley, G. T. N., Onizuka, R., De Meirleir, L. J., Cvitanovic-Sojat, L., Baric, I., Dionisi-Vici, C., Fumic, K., Maradin, M., Tein, I.
|
|
<strong>Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy.</strong>
|
|
Am. J. Med. Genet. 111: 271-284, 2002.
|
|
|
|
|
|
[PubMed: 12210323]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10585]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Onizuka, R., Olpin, S. E., Muntoni, F., Tein, I.
|
|
<strong>OCTN2 mutation (R254X) found in Saudi Arabian kindred: Recurrent mutation or ancient founder mutation?</strong>
|
|
J. Inherit. Metab. Dis. 27: 473-476, 2004.
|
|
|
|
|
|
[PubMed: 15303004]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/B:BOLI.0000037339.25821.87]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lamhonwah, A.-M., Tein, I.
|
|
<strong>Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 252: 396-401, 1998.
|
|
|
|
|
|
[PubMed: 9826541]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1998.9679]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lu, K., Nishimori, H., Nakamura, Y., Shima, K., Kuwajima, M.
|
|
<strong>A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse.</strong>
|
|
Biochem. Biophys. Res. Commun. 252: 590-594, 1998.
|
|
|
|
|
|
[PubMed: 9837751]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1998.9708]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marques, J. S.
|
|
<strong>Dilated cardiomyopathy caused by plasma membrane carnitine transport defect.</strong>
|
|
J. Inherit. Metab. Dis. 21: 428-429, 1998.
|
|
|
|
|
|
[PubMed: 9700603]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1005371028370]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuishi, T., Hirata, K., Terasawa, K., Kato, H., Yoshino, M., Ohtaki, E., Hirose, F., Nonaka, I., Sugiyama, N., Ohta, K.
|
|
<strong>Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy.</strong>
|
|
Neuropediatrics 16: 6-12, 1985.
|
|
|
|
|
|
[PubMed: 3974805]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1055/s-2008-1052536]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McGarry, J. D., Foster, D. W.
|
|
<strong>Systemic carnitine deficiency.</strong>
|
|
New Eng. J. Med. 303: 1413-1415, 1980.
|
|
|
|
|
|
[PubMed: 7432389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198012113032410]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsujimoto, G., Hayakawa, J., Shimane, M., Tsuji, A.
|
|
<strong>Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.</strong>
|
|
Nature Genet. 21: 91-94, 1999.
|
|
|
|
|
|
[PubMed: 9916797]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/5030]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nikaido, H., Horiuchi, M., Hashimoto, N., Saheki, T., Hayakawa, J.
|
|
<strong>Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic carnitine deficiency in mice, on chromosome 11.</strong>
|
|
Mammalian Genome 6: 369-370, 1995.
|
|
|
|
|
|
[PubMed: 7626891]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00364804]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nyhan, W. L.
|
|
<strong>Abnormalities of fatty acid oxidation. (Editorial)</strong>
|
|
New Eng. J. Med. 319: 1344-1346, 1988.
|
|
|
|
|
|
[PubMed: 3185637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198811173192008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okita, K., Tokino, T., Nishimori, H., Miura, K., Nikaido, H., Hayakawa, J., Ono, A., Kuwajima, M., Matsuzawa, Y., Nakamura, Y.
|
|
<strong>Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis.</strong>
|
|
Genomics 33: 289-291, 1996.
|
|
|
|
|
|
[PubMed: 8660978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0194]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rebouche, C. J., Engel, A. G.
|
|
<strong>Primary systemic carnitine deficiency: I. Carnitine biosynthesis.</strong>
|
|
Neurology 31: 813-818, 1981.
|
|
|
|
|
|
[PubMed: 6787460]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.31.7.813]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scaglia, F., Wang, Y., Singh, R. H., Dembure, P. P., Pasquali, M., Fernhoff, P. M., Longo, N.
|
|
<strong>Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency.</strong>
|
|
Genet. Med. 1: 34-39, 1998.
|
|
|
|
|
|
[PubMed: 11261427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-199811000-00008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schimmenti, L. A., Crombez, E. A., Schwahn, B. C., Heese, B. A., Wood, T. C., Schroer, R. J., Bentler, K., Cederbaum, S., Sarafoglou, K., McCann, M., Rinaldo, P., Matern, D., di San Filippo, C. A., Pasquali, M., Berry, S. A., Longo, N.
|
|
<strong>Expanded newborn screening identifies maternal primary carnitine deficiency.</strong>
|
|
Molec. Genet. Metab. 90: 441-445, 2007.
|
|
|
|
|
|
[PubMed: 17126586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2006.10.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shibbani, K., Fahed, A. C., Al-Shaar, L., Arabi, M., Nemer, G., Bitar, F., Majdalani, M.
|
|
<strong>Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype.</strong>
|
|
Clin. Genet. 85: 127-137, 2014.
|
|
|
|
|
|
[PubMed: 23379544]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/cge.12112]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K., Takada, G.
|
|
<strong>Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.</strong>
|
|
Am. J. Hum. Genet. 63: 101-108, 1998.
|
|
|
|
|
|
[PubMed: 9634512]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301911]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stanley, C. A., DeLeeuw, S., Coates, P. M., Vianey-Liaud, C., Divry, P., Bonnefont, J.-P., Saudubray, J.-M., Haymond, M., Trefz, F. K., Breningstall, G. N., Wappner, R. S., Byrd, D. J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S. L., Treem, W. R.
|
|
<strong>Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake.</strong>
|
|
Ann. Neurol. 30: 709-716, 1991.
|
|
|
|
|
|
[PubMed: 1763895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410300512]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tein, I., De Vivo, D. C., Bierman, F., Pulver, P., De Meirleir, L. J., Cvitanovic-Sojat, L., Pagon, R. A., Bertini, E., Dionisi-Vici, C., Servidei, S., Dimauro, S.
|
|
<strong>Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.</strong>
|
|
Pediat. Res. 28: 247-255, 1990.
|
|
|
|
|
|
[PubMed: 2235122]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-199009000-00020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Treem, W. R., Stanley, C. A., Finegold, D. N., Hale, D. E., Coates, P. M.
|
|
<strong>Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts.</strong>
|
|
New Eng. J. Med. 319: 1331-1336, 1988.
|
|
|
|
|
|
[PubMed: 3185635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198811173192006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tripp, M. E., Katcher, M. L., Peters, H. A., Gilbert, E. F., Arya, S., Hodach, R. J., Shug, A. L.
|
|
<strong>Systemic carnitine deficiency presenting as familial endocardial fibroelastosis.</strong>
|
|
New Eng. J. Med. 305: 385-390, 1981.
|
|
|
|
|
|
[PubMed: 7254270]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198108133050707]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waber, L. J., Valle, D., Neill, C., DiMauro, S., Shug, A.
|
|
<strong>Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.</strong>
|
|
J. Pediat. 101: 700-705, 1982.
|
|
|
|
|
|
[PubMed: 7131143]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(82)80294-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, Y., Korman, S. H., Ye, J., Gargus, J. J., Gutman, A., Taroni, F., Garavaglia, B., Longo, N.
|
|
<strong>Phenotype and genotype variation in primary carnitine deficiency.</strong>
|
|
Genet. Med. 3: 387-392, 2001.
|
|
|
|
|
|
[PubMed: 11715001]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-200111000-00002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamak, A. A., Bitar, F., Karam, P., Nemer, G.
|
|
<strong>Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype-phenotype correlation.</strong>
|
|
Clin. Genet. 72: 59-62, 2007.
|
|
|
|
|
|
[PubMed: 17594400]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00814.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zierz, S., Engel, A. G., Romshe, C. A.
|
|
<strong>Assay of acyl-CoA dehydrogenases in muscle and liver and identification of four new cases of medium-chain acyl-CoA dehydrogenase deficiency associated with systemic carnitine deficiency. (Abstract)</strong>
|
|
Muscle Nerve 9: 193, 1986.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 6/26/2014<br>Ada Hamosh - updated : 5/27/2010<br>Cassandra L. Kniffin - reorganized : 5/15/2009<br>Cassandra L. Kniffin - updated : 5/13/2009<br>Ada Hamosh - updated : 6/14/2007<br>Victor A. McKusick - updated : 9/19/2002<br>Ada Hamosh - updated : 1/9/2002<br>Victor A. McKusick - updated : 11/19/1999<br>Victor A. McKusick - updated : 5/14/1999<br>Victor A. McKusick - updated : 3/11/1999<br>Victor A. McKusick - updated : 2/25/1999<br>Victor A. McKusick - updated : 12/22/1998<br>Victor A. McKusick - updated : 7/17/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/3/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 04/30/2020<br>alopez : 09/26/2018<br>carol : 09/09/2016<br>carol : 07/07/2014<br>alopez : 7/1/2014<br>mcolton : 6/30/2014<br>ckniffin : 6/26/2014<br>alopez : 6/2/2010<br>terry : 5/27/2010<br>terry : 8/3/2009<br>carol : 5/15/2009<br>ckniffin : 5/13/2009<br>carol : 9/21/2007<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>alopez : 7/18/2006<br>tkritzer : 9/19/2002<br>tkritzer : 9/19/2002<br>ckniffin : 6/13/2002<br>alopez : 1/17/2002<br>terry : 1/9/2002<br>terry : 2/12/2001<br>alopez : 12/2/1999<br>terry : 11/19/1999<br>mgross : 5/25/1999<br>terry : 5/14/1999<br>carol : 3/24/1999<br>terry : 3/11/1999<br>carol : 3/9/1999<br>terry : 2/25/1999<br>alopez : 1/6/1999<br>alopez : 12/23/1998<br>alopez : 12/22/1998<br>terry : 12/22/1998<br>carol : 7/29/1998<br>carol : 7/21/1998<br>terry : 7/17/1998<br>alopez : 6/10/1997<br>mark : 5/9/1996<br>terry : 5/7/1996<br>terry : 4/30/1996<br>mark : 6/16/1995<br>pfoster : 3/24/1994<br>warfield : 3/8/1994<br>mimadm : 2/19/1994<br>carol : 11/12/1993<br>carol : 7/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|