3798 lines
336 KiB
Text
3798 lines
336 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
|
|
|
|
- #201475 - ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF; ACADVLD
|
|
|
|
|
|
- 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=201475"><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">#201475</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/201475"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</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="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#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=ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF" 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=8768&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/NBK6816/" 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/7410" 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/very-long-chain-acyl-coa-dehydrogenase-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=201475[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/C14.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/C14-1-Elevated-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=26793" 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:0080155" 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/201475" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002140/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0080155" 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:201475" 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> 237997005<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> E71.310<br />
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 26793<br />
|
|
|
|
|
|
<strong>DO:</strong> 0080155<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>
|
|
201475
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF; ACADVLD
|
|
|
|
</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">
|
|
VLCAD DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/139?start=-3&limit=10&highlight=139">
|
|
17p13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
VLCAD deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/201475"> 201475 </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">
|
|
ACADVL
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609575"> 609575 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/201475" 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/201475" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/201475" 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> 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">
|
|
|
|
- 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 /> -
|
|
Cardiac arrest <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397829000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397829000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/410429000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">410429000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I46</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001695</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001695</a>]</span><br /> -
|
|
Sudden cardiac death <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95281009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95281009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085298&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085298</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001645</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001645</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Tachypnea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271823003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271823003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.82</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.06" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.06</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231835</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002789</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002789</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
|
|
Hepatic 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/197321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197321007</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=C0015695&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015695</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 /> -
|
|
Hepatocellular necrosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Muscle weakness associated with fasting or infection <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860062&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860062</a>]</span><br /> -
|
|
Muscle pain with exercise (in older patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850830&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850830</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span><br /> -
|
|
Muscle stiffness (in older patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221170</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003552</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003552</a>]</span><br /> -
|
|
Rhabdomyolysis with exercise (in older patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4021526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4021526</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009045" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009045</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009045" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009045</a>]</span><br /> -
|
|
Myopathic episodes triggered by exercise, fasting, infection, cold temperatures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860066</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 <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br />
|
|
|
|
</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">
|
|
|
|
- Nonketotic hypoglycemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865292&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865292</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001958" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001958</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001958" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001958</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">
|
|
|
|
- Dicarboxylic aciduria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856432&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856432</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003215" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003215</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003215" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003215</a>]</span><br /> -
|
|
Decreased plasma carnitine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5848230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848230</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003234" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003234</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003234" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003234</a>]</span><br /> -
|
|
Decreased very long-chain acyl-CoA dehydrogenase protein and activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860068&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860068</a>]</span><br /> -
|
|
Exercise-induced myoglobinuria in adults <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860069&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860069</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008305" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008305</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008305" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008305</a>]</span><br /> -
|
|
Increased serum creatine kinase in patients with muscle involvement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860070&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860070</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">
|
|
|
|
- Three main clinical forms<br /> -
|
|
Severe, early-onset, usually within the first days of life, with cardiomyopathy and early death<br /> -
|
|
Milder, childhood form, with onset by age 4 years, lesser cardiac involvement, and hypoketotic hypoglycemia<br /> -
|
|
Mild adult form, with onset after age 13 years, no cardiac involvement, and restricted to muscle involvement with rhabdomyolysis<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 very long-chain acyl-CoA dehydrogenase gene (ACAVLD, <a href="/entry/609575#0001">609575.0001</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 very long-chain acyl-CoA dehydrogenase deficiency (ACADVLD) is caused by homozygous or compound heterozygous mutation in the gene encoding very long-chain acyl-CoA dehydrogenase (ACADVL; <a href="/entry/609575">609575</a>) on chromosome 17p13.</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>Inborn errors of mitochondrial fatty acid beta-oxidation include medium-chain acyl-CoA dehydrogenase deficiency (ACADMD; <a href="/entry/201450">201450</a>), short-chain acyl-CoA dehydrogenase deficiency (ACADSD; <a href="/entry/201470">201470</a>), and very long-chain acyl-CoA dehydrogenase deficiency.</p><p>VLCAD deficiency can be classified clinically into 3 forms: a severe early-onset form with high incidence of cardiomyopathy and high mortality; an intermediate form with childhood onset, usually with hypoketotic hypoglycemia and more favorable outcome; and an adult-onset, myopathic form with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria after exercise or fasting (<a href="#1" class="mim-tip-reference" title="Andresen, B. S., Olpin, S., Poorthuis, B. J. H. M., Scholte, H. R., Vianey-Saban, C., Wanders, R., Ijlst, L., Morris, A., Pourfarzam, M., Bartlett, K., Baumgartner, E. R., deKlerk, J. B. C., Schroeder, L. D., Corydon, T. J., Lund, H., Winter, V., Bross, P., Bolund, L., Gregersen, N. <strong>Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.</strong> Am. J. Hum. Genet. 64: 479-494, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9973285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9973285</a>] [<a href="https://doi.org/10.1086/302261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9973285">Andresen et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9973285" 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>Patients reported with long-chain acyl-CoA dehydrogenase (LCAD) deficiency before VLCAD deficiency was defined were later found to have VLCAD deficiency (<a href="#31" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al., 1995</a>; <a href="#30" class="mim-tip-reference" title="Roe, C. R., Ding, J. <strong>Mitochondrial fatty acid oxidation disorders. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001. P. 2305."None>Roe and Ding, 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</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="#18" class="mim-tip-reference" title="Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I., Stanley, C. A. <strong>Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.</strong> Pediat. Res. 19: 666-671, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4022672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4022672</a>] [<a href="https://doi.org/10.1203/00006450-198507000-00006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4022672">Hale et al. (1985)</a> reported 3 unrelated children who presented in early childhood with nonketotic hypoglycemia and episodes of cardiorespiratory arrest associated with fasting. Other features included hepatomegaly, cardiomegaly, and hypotonia. Total plasma carnitine concentration was low. The findings suggested a defect in mitochondrial fatty acid oxidation. Specific assays showed that the activity of long-chain acyl-CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver. Activities of medium-chain, short-chain, and isovaleryl CoA dehydrogenases were normal. With cultured fibroblasts, CO2 evolution from medium-chain and short-chain fatty acids was normal and that from long-chain fatty acids was reduced. As in medium-chain acyl-CoA dehydrogenase deficiency, dicarboxylic acids in the urine and relatively low urinary beta-hydroxybutyrate levels were formed by omega-oxidation of fatty acids in the cytoplasm. The parents had intermediate levels of enzyme activity, suggesting autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4022672" 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="#18" class="mim-tip-reference" title="Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I., Stanley, C. A. <strong>Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.</strong> Pediat. Res. 19: 666-671, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4022672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4022672</a>] [<a href="https://doi.org/10.1203/00006450-198507000-00006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4022672">Hale et al. (1985)</a> also demonstrated deficiency of the long-chain dehydrogenase in fibroblasts from 2 sibs reported by <a href="#21" class="mim-tip-reference" title="Naylor, E. W., Mosovich, L. L., Guthrie, R., Evans, J. E., Tieckelmann, H. <strong>Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycemia: an apparent defect in beta-oxidation of fatty acids.</strong> J. Inherit. Metab. Dis. 3: 19-24, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6774167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6774167</a>] [<a href="https://doi.org/10.1007/BF02312518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6774167">Naylor et al. (1980)</a> with features similar to those in their 3 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4022672+6774167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Treem, W. R., Stanley, C. A., Hale, D. E., Leopold, H. B., Hyams, J. S. <strong>Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency.</strong> Pediatrics 87: 328-333, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2000272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2000272</a>]" pmid="2000272">Treem et al. (1991)</a> described an affected infant and compared the case with 7 previously published cases. The infant had hypotonia and marked cardiac enlargement as well as hypoglycemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2000272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Ribes, A., Riudor, E., Navarro, C., Boronat, M., Marti, M., Hale, D. E. <strong>Fatal outcome in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.</strong> J. Inherit. Metab. Dis. 15: 278-279, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1527994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1527994</a>] [<a href="https://doi.org/10.1007/BF01799642" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1527994">Ribes et al. (1992)</a> provided follow-up information on a patient described by <a href="#29" class="mim-tip-reference" title="Riudor, E., Ribes, A., Boronat, M., Sabado, C., Dominguez, C., Ballabriga, A. <strong>A new case of C(6)-C(14) dicarboxylic aciduria with favourable evolution.</strong> J. Inherit. Metab. Dis. 9 (suppl. 2): 297-299, 1986."None>Riudor et al. (1986)</a>. LCAD deficiency had been documented in the fibroblasts from the patient and treatment with frequent low-fat high-carbohydrate feedings, riboflavin, and carnitine reduced the frequency and intensity of crises. However, the patient developed progressive cardiomegaly and persistent hepatosplenomegaly. Following a crisis similar to those suffered previously, he went into cardiorespiratory arrest at the age of 4.5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1527994" 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="Bertrand, C., Largilliere, C., Zabot, M. T., Mathieu, M., Vianey-Saban, C. <strong>Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.</strong> Biochim. Biophys. Acta 1180: 327-329, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8422439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8422439</a>] [<a href="https://doi.org/10.1016/0925-4439(93)90058-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8422439">Bertrand et al. (1993)</a> reported deficiency of very long-chain acyl-CoA dehydrogenase in a 2-year-old girl with a fatty acid oxidation defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8422439" 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="Yamaguchi, S., Indo, Y., Coates, P. M., Hashimoto, T., Tanaka, K. <strong>Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency.</strong> Pediat. Res. 34: 111-113, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8356011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8356011</a>] [<a href="https://doi.org/10.1203/00006450-199307000-00025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8356011">Yamaguchi et al. (1993)</a> identified VLCAD deficiency in 3 patients previously diagnosed with LCAD deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8356011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Aoyama, T., Uchida, Y., Kelley, R. I., Marble, M., Hofman, K., Tonsgard, J. H., Rhead, W. J., Hashimoto, T. <strong>A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.</strong> Biochem. Biophys. Res. Commun. 191: 1369-1372, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8466512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8466512</a>] [<a href="https://doi.org/10.1006/bbrc.1993.1368" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8466512">Aoyama et al. (1993)</a> reported 2 male patients with VLCAD deficiency as evidenced by in vitro findings of very low palmitoyl-CoA dehydrogenase activity and lack of immunoreactivity to antibody against the VLCAD protein. One patient presented at age 3 months with hypoketotic hypoglycemia, hepatocellular disease, and cardiomyopathy. At autopsy, there was severe hepatocellular injury and marked lipid accumulation in many tissues. The other patient, reported by <a href="#32" class="mim-tip-reference" title="Tonsgard, J. H., Stephens, J. K., Rhead, W. J., Penn, D., Horwitz, A. L., Kirschner, B. S., Whitington, P. F., Berger, S., Tripp, M. E. <strong>Defect in fatty acid oxidation: laboratory and pathologic findings in a patient.</strong> Pediat. Neurol. 7: 125-130, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2059253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2059253</a>] [<a href="https://doi.org/10.1016/0887-8994(91)90009-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2059253">Tonsgard et al. (1991)</a> as an instance of an unexplained defect of long-chain fatty acid oxidation, presented at age 4 months with hypoglycemia, hepatocellular dysfunction, and cardiomyopathy. Laboratory testing revealed hyperammonemia and increased urinary levels of adipate and sebacate. Microscopic examination at autopsy showed lipid accumulation in many tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8466512+2059253" 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="Ogilvie, I., Pourfarzam, M., Jackson, S., Stockdale, C., Bartlett, K., Turnbull, D. M. <strong>Very long-chain acyl coenzyme A dehydrogenase deficiency presenting with exercise-induced myoglobinuria.</strong> Neurology 44: 467-473, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8145917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8145917</a>] [<a href="https://doi.org/10.1212/wnl.44.3_part_1.467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8145917">Ogilvie et al. (1994)</a> reported a 21-year-old man with VLCAD who presented with a 5-year history of exercise-induced muscle pain and myoglobinuria. Residual enzyme activity was approximately 10% of control values. The patient was able to decrease the amount of pain if he ate a carbohydrate snack before or during the exercise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8145917" 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="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al. (1995)</a> used immunoblotting to analyze for VLCAD protein deficiency in skin fibroblasts from 26 patients suspected of having a disorder of mitochondrial beta-oxidation; 7 samples contained undetectable or trace levels of the VLCAD enzyme. Clinically, all patients with VLCAD deficiency exhibited cardiac disease, and at least 4 of them presented with hypertrophic cardiomyopathy. The biochemical work suggested a heterogeneity of mutations causing deficiency in the 7 patients. Six of the 7 patients studied by <a href="#3" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al. (1995)</a> were North American Caucasians, and 1 was Asian. Clinical onset of abnormality was within 4 months after birth, 75% died within 2 months after onset, and all patients had liver dysfunction and cardiac disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" 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="#14" class="mim-tip-reference" title="Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N. <strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong> Pediat. Res. 49: 227-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>] [<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11158518">Fukao et al. (2001)</a> reported a 14-year-old Japanese girl who presented with recurrent myalgia and elevated serum creatine kinase after moderate exercise. She was diagnosed as having a myopathic form of VLCAD deficiency confirmed by genetic analysis (<a href="/entry/609575#0013">609575.0013</a>; <a href="/entry/609575#0014">609575.0014</a>). Her first clinical symptom of the disease appeared at age 6. She had never had hypoglycemic attacks, hepatomegaly, or cardiomyopathy. In vitro functional expression studies showed that the mutant proteins were temperature-sensitive and retained residual activity at 30 degrees Celsius. <a href="#14" class="mim-tip-reference" title="Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N. <strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong> Pediat. Res. 49: 227-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>] [<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11158518">Fukao et al. (2001)</a> concluded that the temperature-sensitive mild mutations in both alleles resulted in this patient's very mild manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11158518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Brown, A., Crowe, L., Andresen, B. S., Anderson, V., Boneh, A. <strong>Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening.</strong> Molec. Genet. Metab. 113: 278-282, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25456746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25456746</a>] [<a href="https://doi.org/10.1016/j.ymgme.2014.10.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25456746">Brown et al. (2014)</a> reported complete neuropsychologic assessment of 7 children with VLCAD deficiency, and 1 additional child with partial assessment. There were 2 females and 6 males in this group. IQs ranged from average to superior. No deficits were found in fine or gross motor skills. One patient had mild language deficit, and 2 had previously required speech therapy. Verbal memory, attention, and executive functioning skills were generally average or above average; visual memory scores were mostly above average. One child was identified as having social skills deficits, and 2 as having behavioral problems. One child rated high on an autism spectrum subscale, and another was formally diagnosed with ASD. <a href="#6" class="mim-tip-reference" title="Brown, A., Crowe, L., Andresen, B. S., Anderson, V., Boneh, A. <strong>Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening.</strong> Molec. Genet. Metab. 113: 278-282, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25456746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25456746</a>] [<a href="https://doi.org/10.1016/j.ymgme.2014.10.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25456746">Brown et al. (2014)</a> concluded that VLCAD deficiency does not have significant impact on cognitive or motor skills. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25456746" 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="Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J. <strong>Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.</strong> Molec. Genet. Metab. 118: 272-281, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27209629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27209629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27209629[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27209629">Pena et al. (2016)</a> retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by newborn screening in the USA and described initial presentations, diagnosis, clinical outcomes, and treatment in a cohort of 52 individuals aged 1 to 18 years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2 of 52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1 to 3 years of age). Of the 14 subjects with elevated creatine kinase, 11 developed rhabdomyolysis. Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27209629" 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="#13" class="mim-tip-reference" title="Evans, M., Andresen, B. S., Nation, J., Boneh, A. <strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong> Molec. Genet. Metab. 118: 282-287, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27246109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27246109</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27246109">Evans et al. (2016)</a> reported on 22 patients with VLCAD deficiency identified by newborn screening in Victoria, Australia. Patients were treated with a low natural-fat diet which was relaxed at age 5 if the patients had been asymptomatic, but supplementation with medium-chain triglyceride (MCT) oil before and after physical activity was recommended to all. All patients were doing well with no episodes of encephalopathy or hypoglycemia, but 3 patients had episodes of muscle pain with or without rhabdomyolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27246109" 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="#24" class="mim-tip-reference" title="Onkenhout, W., Venizelos, V., Scholte, H. R., De Klerk, J. B. C., Poorthuis, B. J. H. M. <strong>Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.</strong> J. Inherit. Metab. Dis. 24: 337-344, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11486898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11486898</a>] [<a href="https://doi.org/10.1023/a:1010592232317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11486898">Onkenhout et al. (2001)</a> determined the fatty acid composition of liver, skeletal muscle, and heart obtained postmortem from patients with deficiency of 1 of 3 types of acyl-CoA dehydrogenase: medium-chain, very long-chain, and multiple (MADD; <a href="/entry/231680">231680</a>). Increased amounts of multiple unsaturated fatty acids were found exclusively in the triglyceride fraction. They could not be detected in the free fatty acid or phospholipid fractions. <a href="#24" class="mim-tip-reference" title="Onkenhout, W., Venizelos, V., Scholte, H. R., De Klerk, J. B. C., Poorthuis, B. J. H. M. <strong>Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.</strong> J. Inherit. Metab. Dis. 24: 337-344, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11486898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11486898</a>] [<a href="https://doi.org/10.1023/a:1010592232317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11486898">Onkenhout et al. (2001)</a> concluded that intermediates of unsaturated fatty acid oxidation that accumulate in these disorders are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation was characteristic for each disease, making fatty acid analysis of total lipid of postmortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who have died unexpectedly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11486898" 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="Elizondo, G., Matern, D., Vockley, J., Harding, C. O., Gillingham, M. B. <strong>Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.</strong> Molec. Genet. Metab. 131: 90-97, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32928639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32928639</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32928639[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32928639">Elizondo et al. (2020)</a> studied plasma acylcarnitine levels in 8 patients with VLCAD deficiency after an overnight fast, after a meal, and after exercise. After an overnight fast, the highest long chain acylcarnitine species level was 14:1. After a meal, the 14:1 level decreased by 62% and after exercise the 14:1 acylcarnitine increased by 133%. <a href="#12" class="mim-tip-reference" title="Elizondo, G., Matern, D., Vockley, J., Harding, C. O., Gillingham, M. B. <strong>Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.</strong> Molec. Genet. Metab. 131: 90-97, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32928639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32928639</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32928639[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32928639">Elizondo et al. (2020)</a> next correlated the sum of long chain acylcarnitines with free fatty acids to after an overnight fast, after a meal, and after exercise to determine the contribution of lipolysis to long chain acylcarnitines in the 8 patients with VLCAD deficiency, 11 patients with CPT2 deficiency (<a href="/entry/255110">255110</a>), and 11 patients with LCHAD deficiency (<a href="/entry/609016">609016</a>). The free fatty acids correlated to total long chain acylcarnitines after overnight fasting but not after exercise, indicating that lipolysis is a significant contributor to acylcarnitine levels with fasting but not exercise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32928639" 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>Deficiency of very long-chain acyl-CoA dehydrogenase is an autosomal recessive disorder (<a href="#31" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" 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="#7" class="mim-tip-reference" title="Costa, C. G., Verhoeven, N. M., Kneepkens, C. M. F., Douwes, A. C., Wanders, R. J. A., Tavares De Almeida, I., Duran, M., Jakobs, C. <strong>Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease.</strong> J. Inherit. Metab. Dis. 19: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8739959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8739959</a>] [<a href="https://doi.org/10.1007/BF01799423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8739959">Costa et al. (1996)</a> described 2 patients with celiac disease and prolonged malnourishment whose urinary organic acid profile during a crisis of metabolic decompensation was similar to those frequently observed in long-chain fatty acid oxidation disorders. The first patient was a girl with a history of vomiting and poor weight gain since the introduction of solid food at the age of 3 months. Clinically she had failure to thrive, hypotonia, and motor retardation. Metabolic screening at the age of 12 months revealed normal amino acids, purines, pyrimidines, and mono- and oligosaccharides. Urinary organic acid analysis revealed an increased excretion of dicarboxylic (DC) and 3-hydroxydicarboxylic (3OHDC) acids without ketonuria. Celiac disease was suspected because of gastrointestinal problems. On a gluten-free diet, the organic acid profile normalized completely. The second patient, a girl, presented with a similar clinical history. Organic acid analysis from the urine collected at 12 months of age revealed hypoketotic dicarboxylic aciduria. After the diagnosis of celiac disease and the introduction of a gluten-free diet, the organic acid profile normalized completely. <a href="#7" class="mim-tip-reference" title="Costa, C. G., Verhoeven, N. M., Kneepkens, C. M. F., Douwes, A. C., Wanders, R. J. A., Tavares De Almeida, I., Duran, M., Jakobs, C. <strong>Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease.</strong> J. Inherit. Metab. Dis. 19: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8739959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8739959</a>] [<a href="https://doi.org/10.1007/BF01799423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8739959">Costa et al. (1996)</a> showed that neither the demonstration of hypoketotic dicarboxylic aciduria nor the analysis of the ratios between urinary DC and 3OHDC acids was sufficient grounds to prove a reliable diagnosis of a potential fatty acid oxidation defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8739959" 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="#23" class="mim-tip-reference" title="Ohashi, Y., Hasegawa, Y., Murayama, K., Ogawa, M., Hasegawa, T., Kawai, M., Sakata, N., Yoshida, K., Yarita, H., Imai, K., Kumagai, I., Murakami, K., Hasegawa, H., Noguchi, S., Nonaka, I., Yamaguchi, S., Nishino, I. <strong>A new diagnostic test for VLCAD deficiency using immunohistochemistry.</strong> Neurology 62: 2209-2213, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15210884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15210884</a>] [<a href="https://doi.org/10.1212/01.wnl.0000130486.54839.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15210884">Ohashi et al. (2004)</a> identified 13 patients with the myopathic form of VLCAD deficiency by using immunohistochemistry to analyze the VLCAD protein in skeletal muscle biopsies. Biochemical analysis confirmed that all 13 patients had low enzymatic activity and reduced amounts of VLCAD protein. Genetic analysis confirmed that they all had mutations in the ACADVL gene. <a href="#23" class="mim-tip-reference" title="Ohashi, Y., Hasegawa, Y., Murayama, K., Ogawa, M., Hasegawa, T., Kawai, M., Sakata, N., Yoshida, K., Yarita, H., Imai, K., Kumagai, I., Murakami, K., Hasegawa, H., Noguchi, S., Nonaka, I., Yamaguchi, S., Nishino, I. <strong>A new diagnostic test for VLCAD deficiency using immunohistochemistry.</strong> Neurology 62: 2209-2213, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15210884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15210884</a>] [<a href="https://doi.org/10.1212/01.wnl.0000130486.54839.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15210884">Ohashi et al. (2004)</a> concluded that the immunohistochemical technique was an effective diagnostic tool for VLCAD deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15210884" 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><a href="#8" class="mim-tip-reference" title="Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S. <strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong> J. Pediat. 133: 247-253, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709714</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70228-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709714">Cox et al. (1998)</a> described a 5-year-old girl with VLCAD deficiency confirmed by genetic analysis (see, e.g., <a href="/entry/609575#0012">609575.0012</a>). She was first seen at 5 months of age with severe hypertrophic cardiomyopathy, hepatomegaly, encephalopathy, and hypotonia. After initial treatment with intravenous glucose and carnitine, the patient thrived on a low-fat diet supplemented with medium-chain triglyceride oil and carnitine and avoidance of fasting. Her ventricular hypertrophy resolved significantly over 1 year, and cognitively, she was in the superior range for age. <a href="#8" class="mim-tip-reference" title="Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S. <strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong> J. Pediat. 133: 247-253, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709714</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70228-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709714">Cox et al. (1998)</a> emphasized that clinical recognition of VLCAD deficiency is important because it is one of the few directly treatable causes of cardiomyopathy in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709714" 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="#26" class="mim-tip-reference" title="Parini, R., Menni, F., Garavaglia, B., Fesslova, V., Melotti, D., Massone, M. L., Lamantea, E., Rimoldi, M., Vizziello, P., Gatti, R. <strong>Acute, severe cardiomyopathy as main symptom of late-onset very long-chain acyl-coenzyme A dehydrogenase deficiency.</strong> Europ. J. Pediat. 157: 992-995, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9877038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9877038</a>] [<a href="https://doi.org/10.1007/s004310050984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9877038">Parini et al. (1998)</a> described a 5-year-old boy with VLCAD deficiency who presented at the age of 5 years with acute severe cardiac and skeletal muscle damage, gross myoglobinuria, and normoglycemia. He was admitted to hospital with severe acute diarrhea, having previously been healthy. Over the next 6 years, he responded well to treatment with 5 meals per day, with medium-chain triglycerides as the main source of lipids, and with raw cornstarch after the last meal of the day. At the time of first presentation in 1992, the patient had been thought to have long-chain acyl-CoA deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9877038" 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>Djouadi et al. (<a href="#11" class="mim-tip-reference" title="Djouadi, F., Bonnefont, J. P., Thuillier, L., Droin, V., Kadhom, N., Munnich, A., Bastin, J. <strong>Correction of fatty acid oxidation in carnitine palmitoyl transferase II-deficient cultured skin fibroblasts by bezafibrate.</strong> Pediat. Res. 54: 446-451, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12840153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12840153</a>] [<a href="https://doi.org/10.1203/01.PDR.0000083001.91588.BB" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12840153">2003</a>, <a href="#9" class="mim-tip-reference" title="Djouadi, F., Aubey, F. Schlemmer, D., Bastin, J. <strong>Peroxisome proliferator activated receptor delta (PPAR-delta) agonist but not PPAR-alpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.</strong> J. Clin. Endocr. Metab. 90: 1791-1797, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15613406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15613406</a>] [<a href="https://doi.org/10.1210/jc.2004-1936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15613406">2005</a>) found that pharmacologic enhancement of a deficient enzyme could be achieved in cells carrying mild mutations of the CPT2 gene (<a href="/entry/600650">600650</a>), which underlies CPT2 deficiency. This was achieved through cell exposure to bezafibrate, a drug widely used for its hypolipidemic action and acting as an agonist of the peroxisomal proliferator-activated receptors (PPARs). Upon pharmacologic activation, PPARs trigger an upregulation of CPT2 gene expression, which results in an increase in CPT2 residual enzyme activity and thereby correction of fatty-acid oxidation (FAO) flux in treated cells. It was thought that this approach might be extended to other FAO defects, since the PPAR signaling pathway controls many different enzymes in the beta-oxidation pathway. <a href="#10" class="mim-tip-reference" title="Djouadi, F., Aubey, F., Schlemmer, D., Ruiter, J. P., Wanders, R. J., Strauss, A. W., Bastin, J. <strong>Bezafibrate increased very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders.</strong> Hum. Molec. Genet. 14: 2695-2703, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115821</a>] [<a href="https://doi.org/10.1093/hmg/ddi303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16115821">Djouadi et al. (2005)</a> found a beneficial effect of bezafibrate in a small series of VLCAD-deficient fibroblast cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15613406+16115821+12840153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Gobin-Limballe, S., Djouadi, F., Aubey, F., Olpin, S., Andresen, B. S., Yamaguchi, S., Mandel, H., Fukao, T., Ruiter, J. P. N., Wanders, R. J. A., McAndrew, R., Kim, J. J., Bastin, J. <strong>Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.</strong> Am. J. Hum. Genet. 81: 1133-1143, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17999356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17999356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17999356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/522375" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17999356">Gobin-Limballe et al. (2007)</a> investigated response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblast cell lines representing 45 mutations. Their results showed that, despite the great diversity of possible consequences of missense mutations for enzyme synthesis, activity, or steady-state level, pharmacologic stimulation of mutant VLCAD gene expression improved the beta-oxidation capacities in a relatively large panel of genotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17999356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated adult men with VLCAD deficiency, <a href="#25" class="mim-tip-reference" title="Orngreen, M. C., Norgaard, M. G., van Engelen, B. G. M., Vistisen, B., Vissing, J. <strong>Effects of IV glucose and oral medium-chain triglyceride in patients with VLCAD deficiency.</strong> Neurology 69: 313-315, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636072</a>] [<a href="https://doi.org/10.1212/01.wnl.0000265854.41013.84" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17636072">Orngreen et al. (2007)</a> found that neither intravenous glucose nor oral medium-chain triglycerides had a beneficial effect on exercise tolerance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636072" 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="Van Calcar, S. C., Sowa, M., Rohr, F., Beazer, J., Setlock, T., Weihe, T. U., Pendyal, S., Wallace, L. S., Hansen, J. G., Stembridge, A., Splett, P., Singh, R. H. <strong>Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): an evidence- and consensus-based approach.</strong> Molec. Genet. Metab. 131: 23-37, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33093005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33093005</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.10.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33093005">Van Calcar et al. (2020)</a> addressed 6 areas for guideline development in the management of VLCAD deficiency, including nutrition recommendations for healthy individuals, management during illness, supplementation, laboratory and clinical monitoring, physical activity and management during pregnancy. The guidelines were based on a review of published literature, a systemic review of gray literature, and an assessment of consensus data from 2 Delphi surveys and one nominal group session. The guidelines included age-based recommendations for fat and energy intake, as well as acceptable fasting intervals, in well individuals. New recommendations for management of VLCAD deficiency included liberalizing the degree of long chain fat restriction for milder cases, promoting breastfeeding for infants with mild or moderate phenotypes, encouraging regular physical activity as tolerated, and supplementing with carnitine only if indicated by low plasma levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33093005" 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="#17" class="mim-tip-reference" title="Guffon, N., Mochel, F., Schiff, M., De Lonlay, P., Douillard, C., Vianey-Saban, C. <strong>Clinical outcomes in a series of 18 patients with long chain fatty acids oxidation disorders treated with triheptanoin for a median duration of 22 months.</strong> Molec. Genet. Metab. 132: 227-233, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33610471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33610471</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.02.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33610471">Guffon et al. (2021)</a> described clinical response to treatment with triheptanoin in 18 patients with disorders of long chain fatty acid oxidation, including 5 with VLCAD deficiency, 5 with LCHAD deficiency (<a href="/entry/609016">609016</a>), 3 with CACT deficiency (<a href="/entry/212138">212138</a>), 3 with CPT II deficiency (<a href="/entry/600649">600649</a>), and 2 with MTP deficiency (<a href="/entry/609015">609015</a>). Treatment duration was for an average of 22 months, with a range of 9 to 228 months. Ten of 12 pediatric patients and 4 of 6 adult patients reported reduction in fatigue and weakness. Eight of 12 pediatric patients and 3 of 6 adult patients experienced reduced intensity of myalgia. Episodes of rhabdomyolysis decreased in 8 of 12 pediatric patients and 3 of 6 adult patients. Of 3 patients who had severe hypoglycemic events in the year prior to starting triheptanoin, none had these events in the year following initiation of therapy. On average, emergency hospital care visits and days of emergency home care were also reduced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33610471" 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>In cultured fibroblasts of 2 patients with VLCAD deficiency, <a href="#2" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T. <strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong> Am. J. Hum. Genet. 57: 273-283, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>]" pmid="7668252">Aoyama et al. (1995)</a> identified a 105-bp deletion in the ACADVL gene (<a href="/entry/609575#0001">609575.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients with VLCAD deficiency, <a href="#31" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al. (1995)</a> identified mutations in the ACADVL gene (<a href="/entry/609575#0002">609575.0002</a>-<a href="/entry/609575#0004">609575.0004</a>). Both patients had originally been diagnosed with long-chain acyl-CoA deficiency (<a href="#18" class="mim-tip-reference" title="Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I., Stanley, C. A. <strong>Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.</strong> Pediat. Res. 19: 666-671, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4022672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4022672</a>] [<a href="https://doi.org/10.1203/00006450-198507000-00006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4022672">Hale et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4022672+7479827" 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="#20" class="mim-tip-reference" title="Mathur, A., Sims, H. F., Gopalakrishnan, D., Gibson, B., Rinaldo, P., Vockley, J., Hug, G., Strauss, A. W. <strong>Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.</strong> Circulation 99: 1337-1343, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077518</a>] [<a href="https://doi.org/10.1161/01.cir.99.10.1337" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10077518">Mathur et al. (1999)</a> identified 21 different mutations in the ACADVL gene in 18 of 37 children with cardiomyopathy, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis. Sixty-seven percent of children had severe dilated or hypertrophic cardiomyopathy at presentation. In 7 patients, only 1 mutation was found despite direct sequencing of all exons. Missense, frameshift, and splice consensus sequence mutations were seen, as well as in-frame deletions. Eighty percent of these mutations were associated with cardiomyopathy. The authors concluded that infantile cardiomyopathy is the most common clinical phenotype for VLCAD deficiency and highlighted the marked allelic heterogeneity in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077518" 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>Of the 52 patients with VLCAD deficiency reported by <a href="#27" class="mim-tip-reference" title="Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J. <strong>Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.</strong> Molec. Genet. Metab. 118: 272-281, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27209629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27209629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27209629[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27209629">Pena et al. (2016)</a>, molecular testing was available for 46. Two mutations were identified in 44 of these while only 1 mutation was identified in the remaining 2. Most (38 of 46, 83%) were compound heterozygous, and of the 50 different alleles reported, 26 were novel. <a href="#13" class="mim-tip-reference" title="Evans, M., Andresen, B. S., Nation, J., Boneh, A. <strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong> Molec. Genet. Metab. 118: 282-287, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27246109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27246109</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27246109">Evans et al. (2016)</a> reported 5 novel mutations among 22 patients with VLCAD deficiency identified in Victoria, Australia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27246109+27209629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#1" class="mim-tip-reference" title="Andresen, B. S., Olpin, S., Poorthuis, B. J. H. M., Scholte, H. R., Vianey-Saban, C., Wanders, R., Ijlst, L., Morris, A., Pourfarzam, M., Bartlett, K., Baumgartner, E. R., deKlerk, J. B. C., Schroeder, L. D., Corydon, T. J., Lund, H., Winter, V., Bross, P., Bolund, L., Gregersen, N. <strong>Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.</strong> Am. J. Hum. Genet. 64: 479-494, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9973285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9973285</a>] [<a href="https://doi.org/10.1086/302261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9973285">Andresen et al. (1999)</a> studied 54 patients with VLCAD, several of whom had been previously reported. Twenty-five patients had the severe childhood form, 75% of whom had onset within the first 3 days of life. These patients had cardiomyopathy (92%), hepatomegaly (80%), hypotonia (52%), and early death (80%). Twenty-one patients had a milder childhood form with onset by 4 years of age. Clinical features in this group included cardiomyopathy (19%), hepatomegaly (62%), rhabdomyolysis or myoglobinuria (14%), hypotonia (62%), and hypoketotic hypoglycemia (76%). Eight patients had a myopathic adult form, with onset after age 13 years. All of these patients had rhabdomyolysis or myoglobinuria, whereas only 13% had cardiomyopathy and 13% had hypotonia. Genotype analysis identified 58 different ACADVL mutations among the whole group. In patients with the severe childhood form of VLCAD, the majority (71%) of mutant alleles were null, whereas in patients with the milder childhood and adult forms of VLCAD, the majority of alleles (82% and 93%, respectively) were predicted to result in some residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9973285" 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="Gregersen, N., Andresen, B. S., Corydon, M. J., Corydon, T. J., Olsen, R. K. J., Bolund, L., Bross, P. <strong>Mutation analysis in mitochondrial fatty acid oxidation defects: exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship.</strong> Hum. Mutat. 18: 169-189, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11524729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11524729</a>] [<a href="https://doi.org/10.1002/humu.1174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11524729">Gregersen et al. (2001)</a> reviewed current understanding of genotype-phenotype relationships in VLCAD, MCAD, and SCAD. They discussed both the structural implications of mutation type and the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. The realization that the effect of the monogene, such as disease-causing mutations in these 3 genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. They stated that the rapid development of mutation detection systems, such as chip technologies, made such profile analyses feasible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11524729" 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>In an abstract, <a href="#19" class="mim-tip-reference" title="Kelly, D., Ogden, M., Hale, D., Hainline, B., Strauss, A. <strong>The molecular basis of human long chain acyl CoA dehydrogenase deficiency. (Abstract)</strong> Am. J. Hum. Genet. 49 (suppl.): 409 only, 1991."None>Kelly et al. (1991)</a> reported the identification of a mutation in the ACADL gene (gln303-to-lys; Q303K) in 3 unrelated patients with LCAD deficiency. No follow-up on this abstract was reported.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Andresen1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andresen, B. S., Olpin, S., Poorthuis, B. J. H. M., Scholte, H. R., Vianey-Saban, C., Wanders, R., Ijlst, L., Morris, A., Pourfarzam, M., Bartlett, K., Baumgartner, E. R., deKlerk, J. B. C., Schroeder, L. D., Corydon, T. J., Lund, H., Winter, V., Bross, P., Bolund, L., Gregersen, N.
|
|
<strong>Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Am. J. Hum. Genet. 64: 479-494, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9973285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9973285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9973285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302261" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Aoyama1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T.
|
|
<strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong>
|
|
Am. J. Hum. Genet. 57: 273-283, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Aoyama1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T.
|
|
<strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong>
|
|
J. Clin. Invest. 95: 2465-2473, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI117947" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Aoyama1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Uchida, Y., Kelley, R. I., Marble, M., Hofman, K., Tonsgard, J. H., Rhead, W. J., Hashimoto, T.
|
|
<strong>A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.</strong>
|
|
Biochem. Biophys. Res. Commun. 191: 1369-1372, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8466512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8466512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8466512" 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.1993.1368" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bertrand1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertrand, C., Largilliere, C., Zabot, M. T., Mathieu, M., Vianey-Saban, C.
|
|
<strong>Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.</strong>
|
|
Biochim. Biophys. Acta 1180: 327-329, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8422439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8422439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8422439" 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(93)90058-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Brown2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, A., Crowe, L., Andresen, B. S., Anderson, V., Boneh, A.
|
|
<strong>Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening.</strong>
|
|
Molec. Genet. Metab. 113: 278-282, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25456746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25456746</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25456746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2014.10.005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Costa1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Costa, C. G., Verhoeven, N. M., Kneepkens, C. M. F., Douwes, A. C., Wanders, R. J. A., Tavares De Almeida, I., Duran, M., Jakobs, C.
|
|
<strong>Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease.</strong>
|
|
J. Inherit. Metab. Dis. 19: 177-180, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8739959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8739959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8739959" 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/BF01799423" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cox1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S.
|
|
<strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
J. Pediat. 133: 247-253, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709714" 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(98)70228-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Djouadi2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Aubey, F. Schlemmer, D., Bastin, J.
|
|
<strong>Peroxisome proliferator activated receptor delta (PPAR-delta) agonist but not PPAR-alpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.</strong>
|
|
J. Clin. Endocr. Metab. 90: 1791-1797, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15613406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15613406</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15613406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-1936" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Djouadi2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Aubey, F., Schlemmer, D., Ruiter, J. P., Wanders, R. J., Strauss, A. W., Bastin, J.
|
|
<strong>Bezafibrate increased very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders.</strong>
|
|
Hum. Molec. Genet. 14: 2695-2703, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115821" 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/ddi303" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Djouadi2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Bonnefont, J. P., Thuillier, L., Droin, V., Kadhom, N., Munnich, A., Bastin, J.
|
|
<strong>Correction of fatty acid oxidation in carnitine palmitoyl transferase II-deficient cultured skin fibroblasts by bezafibrate.</strong>
|
|
Pediat. Res. 54: 446-451, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12840153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12840153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12840153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/01.PDR.0000083001.91588.BB" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Elizondo2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elizondo, G., Matern, D., Vockley, J., Harding, C. O., Gillingham, M. B.
|
|
<strong>Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.</strong>
|
|
Molec. Genet. Metab. 131: 90-97, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32928639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32928639</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32928639[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32928639" 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.2020.09.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Evans2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Evans, M., Andresen, B. S., Nation, J., Boneh, A.
|
|
<strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong>
|
|
Molec. Genet. Metab. 118: 282-287, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27246109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27246109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27246109" 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.2016.05.012" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Fukao2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N.
|
|
<strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong>
|
|
Pediat. Res. 49: 227-231, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11158518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Gobin-Limballe2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gobin-Limballe, S., Djouadi, F., Aubey, F., Olpin, S., Andresen, B. S., Yamaguchi, S., Mandel, H., Fukao, T., Ruiter, J. P. N., Wanders, R. J. A., McAndrew, R., Kim, J. J., Bastin, J.
|
|
<strong>Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.</strong>
|
|
Am. J. Hum. Genet. 81: 1133-1143, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17999356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17999356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17999356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17999356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/522375" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Gregersen2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gregersen, N., Andresen, B. S., Corydon, M. J., Corydon, T. J., Olsen, R. K. J., Bolund, L., Bross, P.
|
|
<strong>Mutation analysis in mitochondrial fatty acid oxidation defects: exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship.</strong>
|
|
Hum. Mutat. 18: 169-189, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11524729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11524729</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11524729" 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.1174" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Guffon2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guffon, N., Mochel, F., Schiff, M., De Lonlay, P., Douillard, C., Vianey-Saban, C.
|
|
<strong>Clinical outcomes in a series of 18 patients with long chain fatty acids oxidation disorders treated with triheptanoin for a median duration of 22 months.</strong>
|
|
Molec. Genet. Metab. 132: 227-233, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33610471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33610471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33610471" 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.2021.02.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Hale1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I., Stanley, C. A.
|
|
<strong>Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.</strong>
|
|
Pediat. Res. 19: 666-671, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4022672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4022672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4022672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-198507000-00006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kelly1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kelly, D., Ogden, M., Hale, D., Hainline, B., Strauss, A.
|
|
<strong>The molecular basis of human long chain acyl CoA dehydrogenase deficiency. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 409 only, 1991.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Mathur1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mathur, A., Sims, H. F., Gopalakrishnan, D., Gibson, B., Rinaldo, P., Vockley, J., Hug, G., Strauss, A. W.
|
|
<strong>Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.</strong>
|
|
Circulation 99: 1337-1343, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1161/01.cir.99.10.1337" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Naylor1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Naylor, E. W., Mosovich, L. L., Guthrie, R., Evans, J. E., Tieckelmann, H.
|
|
<strong>Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycemia: an apparent defect in beta-oxidation of fatty acids.</strong>
|
|
J. Inherit. Metab. Dis. 3: 19-24, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6774167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6774167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6774167" 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/BF02312518" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Ogilvie1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogilvie, I., Pourfarzam, M., Jackson, S., Stockdale, C., Bartlett, K., Turnbull, D. M.
|
|
<strong>Very long-chain acyl coenzyme A dehydrogenase deficiency presenting with exercise-induced myoglobinuria.</strong>
|
|
Neurology 44: 467-473, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8145917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8145917</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8145917" 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.44.3_part_1.467" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Ohashi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohashi, Y., Hasegawa, Y., Murayama, K., Ogawa, M., Hasegawa, T., Kawai, M., Sakata, N., Yoshida, K., Yarita, H., Imai, K., Kumagai, I., Murakami, K., Hasegawa, H., Noguchi, S., Nonaka, I., Yamaguchi, S., Nishino, I.
|
|
<strong>A new diagnostic test for VLCAD deficiency using immunohistochemistry.</strong>
|
|
Neurology 62: 2209-2213, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15210884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15210884</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15210884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000130486.54839.15" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Onkenhout2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Onkenhout, W., Venizelos, V., Scholte, H. R., De Klerk, J. B. C., Poorthuis, B. J. H. M.
|
|
<strong>Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.</strong>
|
|
J. Inherit. Metab. Dis. 24: 337-344, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11486898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11486898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11486898" 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:1010592232317" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Orngreen2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orngreen, M. C., Norgaard, M. G., van Engelen, B. G. M., Vistisen, B., Vissing, J.
|
|
<strong>Effects of IV glucose and oral medium-chain triglyceride in patients with VLCAD deficiency.</strong>
|
|
Neurology 69: 313-315, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636072</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000265854.41013.84" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Parini1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parini, R., Menni, F., Garavaglia, B., Fesslova, V., Melotti, D., Massone, M. L., Lamantea, E., Rimoldi, M., Vizziello, P., Gatti, R.
|
|
<strong>Acute, severe cardiomyopathy as main symptom of late-onset very long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
Europ. J. Pediat. 157: 992-995, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9877038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9877038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9877038" 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/s004310050984" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Pena2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J.
|
|
<strong>Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.</strong>
|
|
Molec. Genet. Metab. 118: 272-281, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27209629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27209629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27209629[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27209629" 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.2016.05.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Ribes1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ribes, A., Riudor, E., Navarro, C., Boronat, M., Marti, M., Hale, D. E.
|
|
<strong>Fatal outcome in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 15: 278-279, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1527994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1527994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1527994" 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/BF01799642" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Riudor1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riudor, E., Ribes, A., Boronat, M., Sabado, C., Dominguez, C., Ballabriga, A.
|
|
<strong>A new case of C(6)-C(14) dicarboxylic aciduria with favourable evolution.</strong>
|
|
J. Inherit. Metab. Dis. 9 (suppl. 2): 297-299, 1986.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Roe2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roe, C. R., Ding, J.
|
|
<strong>Mitochondrial fatty acid oxidation disorders. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. P. 2305.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Strauss1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F.
|
|
<strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Tonsgard1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tonsgard, J. H., Stephens, J. K., Rhead, W. J., Penn, D., Horwitz, A. L., Kirschner, B. S., Whitington, P. F., Berger, S., Tripp, M. E.
|
|
<strong>Defect in fatty acid oxidation: laboratory and pathologic findings in a patient.</strong>
|
|
Pediat. Neurol. 7: 125-130, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2059253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2059253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2059253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0887-8994(91)90009-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Treem1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Treem, W. R., Stanley, C. A., Hale, D. E., Leopold, H. B., Hyams, J. S.
|
|
<strong>Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Pediatrics 87: 328-333, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2000272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2000272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2000272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Van Calcar2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Calcar, S. C., Sowa, M., Rohr, F., Beazer, J., Setlock, T., Weihe, T. U., Pendyal, S., Wallace, L. S., Hansen, J. G., Stembridge, A., Splett, P., Singh, R. H.
|
|
<strong>Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): an evidence- and consensus-based approach.</strong>
|
|
Molec. Genet. Metab. 131: 23-37, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33093005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33093005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33093005" 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.2020.10.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Yamaguchi1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamaguchi, S., Indo, Y., Coates, P. M., Hashimoto, T., Tanaka, K.
|
|
<strong>Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Pediat. Res. 34: 111-113, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8356011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8356011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8356011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-199307000-00025" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 11/17/2021
|
|
</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">
|
|
Hilary J. Vernon - updated : 06/14/2021<br>Hilary J. Vernon - updated : 04/15/2021<br>Ada Hamosh - updated : 12/08/2016<br>Ada Hamosh - updated : 1/20/2015<br>Cassandra L. Kniffin - updated : 12/4/2007<br>Victor A. McKusick - updated : 11/29/2007<br>Cassandra L. Kniffin - reorganized : 9/22/2005<br>Cassandra L. Kniffin - updated : 9/14/2005<br>Patricia A. Hartz - updated : 12/29/2003<br>George E. Tiller - updated : 2/7/2002<br>Victor A. McKusick - updated : 9/26/2001<br>Ada Hamosh - updated : 8/29/2001<br>Ada Hamosh - updated : 4/23/2001<br>Paul Brennan - updated : 7/3/2000<br>Victor A. McKusick - updated : 2/19/1999<br>Orest Hurko - updated : 11/6/1998<br>Victor A. McKusick - updated : 10/1/1998<br>Victor A. McKusick - updated : 12/2/1997<br>Moyra Smith - updated : 5/4/1996
|
|
</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 : 5/27/1993
|
|
</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 : 09/12/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 11/17/2021<br>carol : 06/14/2021<br>joanna : 05/17/2021<br>carol : 04/15/2021<br>carol : 10/19/2017<br>alopez : 12/08/2016<br>carol : 09/07/2016<br>carol : 07/09/2016<br>alopez : 1/20/2015<br>carol : 4/27/2011<br>carol : 4/22/2011<br>wwang : 12/7/2007<br>ckniffin : 12/4/2007<br>alopez : 11/30/2007<br>alopez : 11/29/2007<br>alopez : 11/29/2007<br>carol : 9/22/2005<br>ckniffin : 9/14/2005<br>carol : 3/17/2004<br>tkritzer : 3/11/2004<br>tkritzer : 3/10/2004<br>carol : 12/29/2003<br>ckniffin : 6/13/2002<br>carol : 4/30/2002<br>cwells : 2/18/2002<br>cwells : 2/7/2002<br>carol : 10/4/2001<br>mcapotos : 10/1/2001<br>terry : 9/26/2001<br>cwells : 9/14/2001<br>cwells : 9/14/2001<br>cwells : 9/4/2001<br>terry : 8/29/2001<br>cwells : 5/22/2001<br>cwells : 5/9/2001<br>cwells : 5/7/2001<br>terry : 4/23/2001<br>alopez : 7/3/2000<br>mcapotos : 6/5/2000<br>mcapotos : 5/26/2000<br>carol : 5/22/2000<br>terry : 5/22/2000<br>terry : 6/9/1999<br>terry : 2/19/1999<br>carol : 11/25/1998<br>terry : 11/6/1998<br>carol : 10/5/1998<br>terry : 10/1/1998<br>terry : 6/4/1998<br>alopez : 12/15/1997<br>alopez : 12/15/1997<br>dholmes : 12/4/1997<br>carol : 7/13/1996<br>mark : 5/31/1996<br>mark : 5/31/1996<br>mark : 5/31/1996<br>carol : 5/22/1996<br>mark : 5/6/1996<br>carol : 5/4/1996<br>mark : 4/23/1996<br>mark : 1/25/1996<br>terry : 1/23/1996<br>mark : 12/6/1995<br>mark : 12/6/1995<br>mark : 8/30/1995<br>jason : 6/27/1994<br>mimadm : 3/11/1994<br>carol : 5/27/1993
|
|
</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> 201475
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF; ACADVLD
|
|
|
|
</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">
|
|
VLCAD DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 237997005;
|
|
|
|
|
|
<strong>ICD10CM:</strong> E71.310;
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 26793;
|
|
|
|
|
|
<strong>DO:</strong> 0080155;
|
|
|
|
|
|
</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">
|
|
17p13.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
VLCAD deficiency
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
201475
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
ACADVL
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609575
|
|
</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 very long-chain acyl-CoA dehydrogenase deficiency (ACADVLD) is caused by homozygous or compound heterozygous mutation in the gene encoding very long-chain acyl-CoA dehydrogenase (ACADVL; 609575) on chromosome 17p13.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Inborn errors of mitochondrial fatty acid beta-oxidation include medium-chain acyl-CoA dehydrogenase deficiency (ACADMD; 201450), short-chain acyl-CoA dehydrogenase deficiency (ACADSD; 201470), and very long-chain acyl-CoA dehydrogenase deficiency.</p><p>VLCAD deficiency can be classified clinically into 3 forms: a severe early-onset form with high incidence of cardiomyopathy and high mortality; an intermediate form with childhood onset, usually with hypoketotic hypoglycemia and more favorable outcome; and an adult-onset, myopathic form with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria after exercise or fasting (Andresen et al., 1999). </p><p>Patients reported with long-chain acyl-CoA dehydrogenase (LCAD) deficiency before VLCAD deficiency was defined were later found to have VLCAD deficiency (Strauss et al., 1995; Roe and Ding, 2001). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hale et al. (1985) reported 3 unrelated children who presented in early childhood with nonketotic hypoglycemia and episodes of cardiorespiratory arrest associated with fasting. Other features included hepatomegaly, cardiomegaly, and hypotonia. Total plasma carnitine concentration was low. The findings suggested a defect in mitochondrial fatty acid oxidation. Specific assays showed that the activity of long-chain acyl-CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver. Activities of medium-chain, short-chain, and isovaleryl CoA dehydrogenases were normal. With cultured fibroblasts, CO2 evolution from medium-chain and short-chain fatty acids was normal and that from long-chain fatty acids was reduced. As in medium-chain acyl-CoA dehydrogenase deficiency, dicarboxylic acids in the urine and relatively low urinary beta-hydroxybutyrate levels were formed by omega-oxidation of fatty acids in the cytoplasm. The parents had intermediate levels of enzyme activity, suggesting autosomal recessive inheritance. </p><p>Hale et al. (1985) also demonstrated deficiency of the long-chain dehydrogenase in fibroblasts from 2 sibs reported by Naylor et al. (1980) with features similar to those in their 3 patients. </p><p>Treem et al. (1991) described an affected infant and compared the case with 7 previously published cases. The infant had hypotonia and marked cardiac enlargement as well as hypoglycemia. </p><p>Ribes et al. (1992) provided follow-up information on a patient described by Riudor et al. (1986). LCAD deficiency had been documented in the fibroblasts from the patient and treatment with frequent low-fat high-carbohydrate feedings, riboflavin, and carnitine reduced the frequency and intensity of crises. However, the patient developed progressive cardiomegaly and persistent hepatosplenomegaly. Following a crisis similar to those suffered previously, he went into cardiorespiratory arrest at the age of 4.5 years. </p><p>Bertrand et al. (1993) reported deficiency of very long-chain acyl-CoA dehydrogenase in a 2-year-old girl with a fatty acid oxidation defect. </p><p>Yamaguchi et al. (1993) identified VLCAD deficiency in 3 patients previously diagnosed with LCAD deficiency. </p><p>Aoyama et al. (1993) reported 2 male patients with VLCAD deficiency as evidenced by in vitro findings of very low palmitoyl-CoA dehydrogenase activity and lack of immunoreactivity to antibody against the VLCAD protein. One patient presented at age 3 months with hypoketotic hypoglycemia, hepatocellular disease, and cardiomyopathy. At autopsy, there was severe hepatocellular injury and marked lipid accumulation in many tissues. The other patient, reported by Tonsgard et al. (1991) as an instance of an unexplained defect of long-chain fatty acid oxidation, presented at age 4 months with hypoglycemia, hepatocellular dysfunction, and cardiomyopathy. Laboratory testing revealed hyperammonemia and increased urinary levels of adipate and sebacate. Microscopic examination at autopsy showed lipid accumulation in many tissues. </p><p>Ogilvie et al. (1994) reported a 21-year-old man with VLCAD who presented with a 5-year history of exercise-induced muscle pain and myoglobinuria. Residual enzyme activity was approximately 10% of control values. The patient was able to decrease the amount of pain if he ate a carbohydrate snack before or during the exercise. </p><p>Aoyama et al. (1995) used immunoblotting to analyze for VLCAD protein deficiency in skin fibroblasts from 26 patients suspected of having a disorder of mitochondrial beta-oxidation; 7 samples contained undetectable or trace levels of the VLCAD enzyme. Clinically, all patients with VLCAD deficiency exhibited cardiac disease, and at least 4 of them presented with hypertrophic cardiomyopathy. The biochemical work suggested a heterogeneity of mutations causing deficiency in the 7 patients. Six of the 7 patients studied by Aoyama et al. (1995) were North American Caucasians, and 1 was Asian. Clinical onset of abnormality was within 4 months after birth, 75% died within 2 months after onset, and all patients had liver dysfunction and cardiac disease. </p><p>Fukao et al. (2001) reported a 14-year-old Japanese girl who presented with recurrent myalgia and elevated serum creatine kinase after moderate exercise. She was diagnosed as having a myopathic form of VLCAD deficiency confirmed by genetic analysis (609575.0013; 609575.0014). Her first clinical symptom of the disease appeared at age 6. She had never had hypoglycemic attacks, hepatomegaly, or cardiomyopathy. In vitro functional expression studies showed that the mutant proteins were temperature-sensitive and retained residual activity at 30 degrees Celsius. Fukao et al. (2001) concluded that the temperature-sensitive mild mutations in both alleles resulted in this patient's very mild manifestations. </p><p>Brown et al. (2014) reported complete neuropsychologic assessment of 7 children with VLCAD deficiency, and 1 additional child with partial assessment. There were 2 females and 6 males in this group. IQs ranged from average to superior. No deficits were found in fine or gross motor skills. One patient had mild language deficit, and 2 had previously required speech therapy. Verbal memory, attention, and executive functioning skills were generally average or above average; visual memory scores were mostly above average. One child was identified as having social skills deficits, and 2 as having behavioral problems. One child rated high on an autism spectrum subscale, and another was formally diagnosed with ASD. Brown et al. (2014) concluded that VLCAD deficiency does not have significant impact on cognitive or motor skills. </p><p>Pena et al. (2016) retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by newborn screening in the USA and described initial presentations, diagnosis, clinical outcomes, and treatment in a cohort of 52 individuals aged 1 to 18 years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2 of 52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1 to 3 years of age). Of the 14 subjects with elevated creatine kinase, 11 developed rhabdomyolysis. Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified. </p><p>Evans et al. (2016) reported on 22 patients with VLCAD deficiency identified by newborn screening in Victoria, Australia. Patients were treated with a low natural-fat diet which was relaxed at age 5 if the patients had been asymptomatic, but supplementation with medium-chain triglyceride (MCT) oil before and after physical activity was recommended to all. All patients were doing well with no episodes of encephalopathy or hypoglycemia, but 3 patients had episodes of muscle pain with or without rhabdomyolysis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Onkenhout et al. (2001) determined the fatty acid composition of liver, skeletal muscle, and heart obtained postmortem from patients with deficiency of 1 of 3 types of acyl-CoA dehydrogenase: medium-chain, very long-chain, and multiple (MADD; 231680). Increased amounts of multiple unsaturated fatty acids were found exclusively in the triglyceride fraction. They could not be detected in the free fatty acid or phospholipid fractions. Onkenhout et al. (2001) concluded that intermediates of unsaturated fatty acid oxidation that accumulate in these disorders are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation was characteristic for each disease, making fatty acid analysis of total lipid of postmortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who have died unexpectedly. </p><p>Elizondo et al. (2020) studied plasma acylcarnitine levels in 8 patients with VLCAD deficiency after an overnight fast, after a meal, and after exercise. After an overnight fast, the highest long chain acylcarnitine species level was 14:1. After a meal, the 14:1 level decreased by 62% and after exercise the 14:1 acylcarnitine increased by 133%. Elizondo et al. (2020) next correlated the sum of long chain acylcarnitines with free fatty acids to after an overnight fast, after a meal, and after exercise to determine the contribution of lipolysis to long chain acylcarnitines in the 8 patients with VLCAD deficiency, 11 patients with CPT2 deficiency (255110), and 11 patients with LCHAD deficiency (609016). The free fatty acids correlated to total long chain acylcarnitines after overnight fasting but not after exercise, indicating that lipolysis is a significant contributor to acylcarnitine levels with fasting but not exercise. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Deficiency of very long-chain acyl-CoA dehydrogenase is an autosomal recessive disorder (Strauss et al., 1995). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Costa et al. (1996) described 2 patients with celiac disease and prolonged malnourishment whose urinary organic acid profile during a crisis of metabolic decompensation was similar to those frequently observed in long-chain fatty acid oxidation disorders. The first patient was a girl with a history of vomiting and poor weight gain since the introduction of solid food at the age of 3 months. Clinically she had failure to thrive, hypotonia, and motor retardation. Metabolic screening at the age of 12 months revealed normal amino acids, purines, pyrimidines, and mono- and oligosaccharides. Urinary organic acid analysis revealed an increased excretion of dicarboxylic (DC) and 3-hydroxydicarboxylic (3OHDC) acids without ketonuria. Celiac disease was suspected because of gastrointestinal problems. On a gluten-free diet, the organic acid profile normalized completely. The second patient, a girl, presented with a similar clinical history. Organic acid analysis from the urine collected at 12 months of age revealed hypoketotic dicarboxylic aciduria. After the diagnosis of celiac disease and the introduction of a gluten-free diet, the organic acid profile normalized completely. Costa et al. (1996) showed that neither the demonstration of hypoketotic dicarboxylic aciduria nor the analysis of the ratios between urinary DC and 3OHDC acids was sufficient grounds to prove a reliable diagnosis of a potential fatty acid oxidation defect. </p><p>Ohashi et al. (2004) identified 13 patients with the myopathic form of VLCAD deficiency by using immunohistochemistry to analyze the VLCAD protein in skeletal muscle biopsies. Biochemical analysis confirmed that all 13 patients had low enzymatic activity and reduced amounts of VLCAD protein. Genetic analysis confirmed that they all had mutations in the ACADVL gene. Ohashi et al. (2004) concluded that the immunohistochemical technique was an effective diagnostic tool for VLCAD deficiency. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cox et al. (1998) described a 5-year-old girl with VLCAD deficiency confirmed by genetic analysis (see, e.g., 609575.0012). She was first seen at 5 months of age with severe hypertrophic cardiomyopathy, hepatomegaly, encephalopathy, and hypotonia. After initial treatment with intravenous glucose and carnitine, the patient thrived on a low-fat diet supplemented with medium-chain triglyceride oil and carnitine and avoidance of fasting. Her ventricular hypertrophy resolved significantly over 1 year, and cognitively, she was in the superior range for age. Cox et al. (1998) emphasized that clinical recognition of VLCAD deficiency is important because it is one of the few directly treatable causes of cardiomyopathy in children. </p><p>Parini et al. (1998) described a 5-year-old boy with VLCAD deficiency who presented at the age of 5 years with acute severe cardiac and skeletal muscle damage, gross myoglobinuria, and normoglycemia. He was admitted to hospital with severe acute diarrhea, having previously been healthy. Over the next 6 years, he responded well to treatment with 5 meals per day, with medium-chain triglycerides as the main source of lipids, and with raw cornstarch after the last meal of the day. At the time of first presentation in 1992, the patient had been thought to have long-chain acyl-CoA deficiency. </p><p>Djouadi et al. (2003, 2005) found that pharmacologic enhancement of a deficient enzyme could be achieved in cells carrying mild mutations of the CPT2 gene (600650), which underlies CPT2 deficiency. This was achieved through cell exposure to bezafibrate, a drug widely used for its hypolipidemic action and acting as an agonist of the peroxisomal proliferator-activated receptors (PPARs). Upon pharmacologic activation, PPARs trigger an upregulation of CPT2 gene expression, which results in an increase in CPT2 residual enzyme activity and thereby correction of fatty-acid oxidation (FAO) flux in treated cells. It was thought that this approach might be extended to other FAO defects, since the PPAR signaling pathway controls many different enzymes in the beta-oxidation pathway. Djouadi et al. (2005) found a beneficial effect of bezafibrate in a small series of VLCAD-deficient fibroblast cell lines. </p><p>Gobin-Limballe et al. (2007) investigated response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblast cell lines representing 45 mutations. Their results showed that, despite the great diversity of possible consequences of missense mutations for enzyme synthesis, activity, or steady-state level, pharmacologic stimulation of mutant VLCAD gene expression improved the beta-oxidation capacities in a relatively large panel of genotypes. </p><p>In 2 unrelated adult men with VLCAD deficiency, Orngreen et al. (2007) found that neither intravenous glucose nor oral medium-chain triglycerides had a beneficial effect on exercise tolerance. </p><p>Van Calcar et al. (2020) addressed 6 areas for guideline development in the management of VLCAD deficiency, including nutrition recommendations for healthy individuals, management during illness, supplementation, laboratory and clinical monitoring, physical activity and management during pregnancy. The guidelines were based on a review of published literature, a systemic review of gray literature, and an assessment of consensus data from 2 Delphi surveys and one nominal group session. The guidelines included age-based recommendations for fat and energy intake, as well as acceptable fasting intervals, in well individuals. New recommendations for management of VLCAD deficiency included liberalizing the degree of long chain fat restriction for milder cases, promoting breastfeeding for infants with mild or moderate phenotypes, encouraging regular physical activity as tolerated, and supplementing with carnitine only if indicated by low plasma levels. </p><p>Guffon et al. (2021) described clinical response to treatment with triheptanoin in 18 patients with disorders of long chain fatty acid oxidation, including 5 with VLCAD deficiency, 5 with LCHAD deficiency (609016), 3 with CACT deficiency (212138), 3 with CPT II deficiency (600649), and 2 with MTP deficiency (609015). Treatment duration was for an average of 22 months, with a range of 9 to 228 months. Ten of 12 pediatric patients and 4 of 6 adult patients reported reduction in fatigue and weakness. Eight of 12 pediatric patients and 3 of 6 adult patients experienced reduced intensity of myalgia. Episodes of rhabdomyolysis decreased in 8 of 12 pediatric patients and 3 of 6 adult patients. Of 3 patients who had severe hypoglycemic events in the year prior to starting triheptanoin, none had these events in the year following initiation of therapy. On average, emergency hospital care visits and days of emergency home care were also reduced. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In cultured fibroblasts of 2 patients with VLCAD deficiency, Aoyama et al. (1995) identified a 105-bp deletion in the ACADVL gene (609575.0001). </p><p>In 2 unrelated patients with VLCAD deficiency, Strauss et al. (1995) identified mutations in the ACADVL gene (609575.0002-609575.0004). Both patients had originally been diagnosed with long-chain acyl-CoA deficiency (Hale et al., 1985). </p><p>Mathur et al. (1999) identified 21 different mutations in the ACADVL gene in 18 of 37 children with cardiomyopathy, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis. Sixty-seven percent of children had severe dilated or hypertrophic cardiomyopathy at presentation. In 7 patients, only 1 mutation was found despite direct sequencing of all exons. Missense, frameshift, and splice consensus sequence mutations were seen, as well as in-frame deletions. Eighty percent of these mutations were associated with cardiomyopathy. The authors concluded that infantile cardiomyopathy is the most common clinical phenotype for VLCAD deficiency and highlighted the marked allelic heterogeneity in this disorder. </p><p>Of the 52 patients with VLCAD deficiency reported by Pena et al. (2016), molecular testing was available for 46. Two mutations were identified in 44 of these while only 1 mutation was identified in the remaining 2. Most (38 of 46, 83%) were compound heterozygous, and of the 50 different alleles reported, 26 were novel. Evans et al. (2016) reported 5 novel mutations among 22 patients with VLCAD deficiency identified in Victoria, Australia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Andresen et al. (1999) studied 54 patients with VLCAD, several of whom had been previously reported. Twenty-five patients had the severe childhood form, 75% of whom had onset within the first 3 days of life. These patients had cardiomyopathy (92%), hepatomegaly (80%), hypotonia (52%), and early death (80%). Twenty-one patients had a milder childhood form with onset by 4 years of age. Clinical features in this group included cardiomyopathy (19%), hepatomegaly (62%), rhabdomyolysis or myoglobinuria (14%), hypotonia (62%), and hypoketotic hypoglycemia (76%). Eight patients had a myopathic adult form, with onset after age 13 years. All of these patients had rhabdomyolysis or myoglobinuria, whereas only 13% had cardiomyopathy and 13% had hypotonia. Genotype analysis identified 58 different ACADVL mutations among the whole group. In patients with the severe childhood form of VLCAD, the majority (71%) of mutant alleles were null, whereas in patients with the milder childhood and adult forms of VLCAD, the majority of alleles (82% and 93%, respectively) were predicted to result in some residual enzyme activity. </p><p>Gregersen et al. (2001) reviewed current understanding of genotype-phenotype relationships in VLCAD, MCAD, and SCAD. They discussed both the structural implications of mutation type and the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. The realization that the effect of the monogene, such as disease-causing mutations in these 3 genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. They stated that the rapid development of mutation detection systems, such as chip technologies, made such profile analyses feasible. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In an abstract, Kelly et al. (1991) reported the identification of a mutation in the ACADL gene (gln303-to-lys; Q303K) in 3 unrelated patients with LCAD deficiency. No follow-up on this abstract was reported.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andresen, B. S., Olpin, S., Poorthuis, B. J. H. M., Scholte, H. R., Vianey-Saban, C., Wanders, R., Ijlst, L., Morris, A., Pourfarzam, M., Bartlett, K., Baumgartner, E. R., deKlerk, J. B. C., Schroeder, L. D., Corydon, T. J., Lund, H., Winter, V., Bross, P., Bolund, L., Gregersen, N.
|
|
<strong>Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Am. J. Hum. Genet. 64: 479-494, 1999.
|
|
|
|
|
|
[PubMed: 9973285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302261]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T.
|
|
<strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong>
|
|
Am. J. Hum. Genet. 57: 273-283, 1995.
|
|
|
|
|
|
[PubMed: 7668252]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T.
|
|
<strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong>
|
|
J. Clin. Invest. 95: 2465-2473, 1995.
|
|
|
|
|
|
[PubMed: 7769092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI117947]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Uchida, Y., Kelley, R. I., Marble, M., Hofman, K., Tonsgard, J. H., Rhead, W. J., Hashimoto, T.
|
|
<strong>A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.</strong>
|
|
Biochem. Biophys. Res. Commun. 191: 1369-1372, 1993.
|
|
|
|
|
|
[PubMed: 8466512]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1993.1368]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertrand, C., Largilliere, C., Zabot, M. T., Mathieu, M., Vianey-Saban, C.
|
|
<strong>Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.</strong>
|
|
Biochim. Biophys. Acta 1180: 327-329, 1993.
|
|
|
|
|
|
[PubMed: 8422439]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0925-4439(93)90058-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, A., Crowe, L., Andresen, B. S., Anderson, V., Boneh, A.
|
|
<strong>Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening.</strong>
|
|
Molec. Genet. Metab. 113: 278-282, 2014.
|
|
|
|
|
|
[PubMed: 25456746]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2014.10.005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Costa, C. G., Verhoeven, N. M., Kneepkens, C. M. F., Douwes, A. C., Wanders, R. J. A., Tavares De Almeida, I., Duran, M., Jakobs, C.
|
|
<strong>Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease.</strong>
|
|
J. Inherit. Metab. Dis. 19: 177-180, 1996.
|
|
|
|
|
|
[PubMed: 8739959]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01799423]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S.
|
|
<strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
J. Pediat. 133: 247-253, 1998.
|
|
|
|
|
|
[PubMed: 9709714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70228-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Aubey, F. Schlemmer, D., Bastin, J.
|
|
<strong>Peroxisome proliferator activated receptor delta (PPAR-delta) agonist but not PPAR-alpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.</strong>
|
|
J. Clin. Endocr. Metab. 90: 1791-1797, 2005.
|
|
|
|
|
|
[PubMed: 15613406]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-1936]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Aubey, F., Schlemmer, D., Ruiter, J. P., Wanders, R. J., Strauss, A. W., Bastin, J.
|
|
<strong>Bezafibrate increased very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders.</strong>
|
|
Hum. Molec. Genet. 14: 2695-2703, 2005.
|
|
|
|
|
|
[PubMed: 16115821]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi303]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Djouadi, F., Bonnefont, J. P., Thuillier, L., Droin, V., Kadhom, N., Munnich, A., Bastin, J.
|
|
<strong>Correction of fatty acid oxidation in carnitine palmitoyl transferase II-deficient cultured skin fibroblasts by bezafibrate.</strong>
|
|
Pediat. Res. 54: 446-451, 2003.
|
|
|
|
|
|
[PubMed: 12840153]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/01.PDR.0000083001.91588.BB]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elizondo, G., Matern, D., Vockley, J., Harding, C. O., Gillingham, M. B.
|
|
<strong>Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.</strong>
|
|
Molec. Genet. Metab. 131: 90-97, 2020.
|
|
|
|
|
|
[PubMed: 32928639]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2020.09.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, M., Andresen, B. S., Nation, J., Boneh, A.
|
|
<strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong>
|
|
Molec. Genet. Metab. 118: 282-287, 2016.
|
|
|
|
|
|
[PubMed: 27246109]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2016.05.012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N.
|
|
<strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong>
|
|
Pediat. Res. 49: 227-231, 2001.
|
|
|
|
|
|
[PubMed: 11158518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-200102000-00016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gobin-Limballe, S., Djouadi, F., Aubey, F., Olpin, S., Andresen, B. S., Yamaguchi, S., Mandel, H., Fukao, T., Ruiter, J. P. N., Wanders, R. J. A., McAndrew, R., Kim, J. J., Bastin, J.
|
|
<strong>Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.</strong>
|
|
Am. J. Hum. Genet. 81: 1133-1143, 2007.
|
|
|
|
|
|
[PubMed: 17999356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/522375]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gregersen, N., Andresen, B. S., Corydon, M. J., Corydon, T. J., Olsen, R. K. J., Bolund, L., Bross, P.
|
|
<strong>Mutation analysis in mitochondrial fatty acid oxidation defects: exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship.</strong>
|
|
Hum. Mutat. 18: 169-189, 2001.
|
|
|
|
|
|
[PubMed: 11524729]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1174]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guffon, N., Mochel, F., Schiff, M., De Lonlay, P., Douillard, C., Vianey-Saban, C.
|
|
<strong>Clinical outcomes in a series of 18 patients with long chain fatty acids oxidation disorders treated with triheptanoin for a median duration of 22 months.</strong>
|
|
Molec. Genet. Metab. 132: 227-233, 2021.
|
|
|
|
|
|
[PubMed: 33610471]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2021.02.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I., Stanley, C. A.
|
|
<strong>Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.</strong>
|
|
Pediat. Res. 19: 666-671, 1985.
|
|
|
|
|
|
[PubMed: 4022672]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-198507000-00006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kelly, D., Ogden, M., Hale, D., Hainline, B., Strauss, A.
|
|
<strong>The molecular basis of human long chain acyl CoA dehydrogenase deficiency. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 409 only, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mathur, A., Sims, H. F., Gopalakrishnan, D., Gibson, B., Rinaldo, P., Vockley, J., Hug, G., Strauss, A. W.
|
|
<strong>Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.</strong>
|
|
Circulation 99: 1337-1343, 1999.
|
|
|
|
|
|
[PubMed: 10077518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/01.cir.99.10.1337]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naylor, E. W., Mosovich, L. L., Guthrie, R., Evans, J. E., Tieckelmann, H.
|
|
<strong>Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycemia: an apparent defect in beta-oxidation of fatty acids.</strong>
|
|
J. Inherit. Metab. Dis. 3: 19-24, 1980.
|
|
|
|
|
|
[PubMed: 6774167]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF02312518]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogilvie, I., Pourfarzam, M., Jackson, S., Stockdale, C., Bartlett, K., Turnbull, D. M.
|
|
<strong>Very long-chain acyl coenzyme A dehydrogenase deficiency presenting with exercise-induced myoglobinuria.</strong>
|
|
Neurology 44: 467-473, 1994.
|
|
|
|
|
|
[PubMed: 8145917]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.44.3_part_1.467]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohashi, Y., Hasegawa, Y., Murayama, K., Ogawa, M., Hasegawa, T., Kawai, M., Sakata, N., Yoshida, K., Yarita, H., Imai, K., Kumagai, I., Murakami, K., Hasegawa, H., Noguchi, S., Nonaka, I., Yamaguchi, S., Nishino, I.
|
|
<strong>A new diagnostic test for VLCAD deficiency using immunohistochemistry.</strong>
|
|
Neurology 62: 2209-2213, 2004.
|
|
|
|
|
|
[PubMed: 15210884]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000130486.54839.15]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Onkenhout, W., Venizelos, V., Scholte, H. R., De Klerk, J. B. C., Poorthuis, B. J. H. M.
|
|
<strong>Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.</strong>
|
|
J. Inherit. Metab. Dis. 24: 337-344, 2001.
|
|
|
|
|
|
[PubMed: 11486898]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1010592232317]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orngreen, M. C., Norgaard, M. G., van Engelen, B. G. M., Vistisen, B., Vissing, J.
|
|
<strong>Effects of IV glucose and oral medium-chain triglyceride in patients with VLCAD deficiency.</strong>
|
|
Neurology 69: 313-315, 2007.
|
|
|
|
|
|
[PubMed: 17636072]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000265854.41013.84]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parini, R., Menni, F., Garavaglia, B., Fesslova, V., Melotti, D., Massone, M. L., Lamantea, E., Rimoldi, M., Vizziello, P., Gatti, R.
|
|
<strong>Acute, severe cardiomyopathy as main symptom of late-onset very long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
Europ. J. Pediat. 157: 992-995, 1998.
|
|
|
|
|
|
[PubMed: 9877038]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004310050984]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J.
|
|
<strong>Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.</strong>
|
|
Molec. Genet. Metab. 118: 272-281, 2016.
|
|
|
|
|
|
[PubMed: 27209629]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2016.05.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ribes, A., Riudor, E., Navarro, C., Boronat, M., Marti, M., Hale, D. E.
|
|
<strong>Fatal outcome in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 15: 278-279, 1992.
|
|
|
|
|
|
[PubMed: 1527994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01799642]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riudor, E., Ribes, A., Boronat, M., Sabado, C., Dominguez, C., Ballabriga, A.
|
|
<strong>A new case of C(6)-C(14) dicarboxylic aciduria with favourable evolution.</strong>
|
|
J. Inherit. Metab. Dis. 9 (suppl. 2): 297-299, 1986.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roe, C. R., Ding, J.
|
|
<strong>Mitochondrial fatty acid oxidation disorders. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. P. 2305.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F.
|
|
<strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.
|
|
|
|
|
|
[PubMed: 7479827]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.92.23.10496]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tonsgard, J. H., Stephens, J. K., Rhead, W. J., Penn, D., Horwitz, A. L., Kirschner, B. S., Whitington, P. F., Berger, S., Tripp, M. E.
|
|
<strong>Defect in fatty acid oxidation: laboratory and pathologic findings in a patient.</strong>
|
|
Pediat. Neurol. 7: 125-130, 1991.
|
|
|
|
|
|
[PubMed: 2059253]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0887-8994(91)90009-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Treem, W. R., Stanley, C. A., Hale, D. E., Leopold, H. B., Hyams, J. S.
|
|
<strong>Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Pediatrics 87: 328-333, 1991.
|
|
|
|
|
|
[PubMed: 2000272]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Calcar, S. C., Sowa, M., Rohr, F., Beazer, J., Setlock, T., Weihe, T. U., Pendyal, S., Wallace, L. S., Hansen, J. G., Stembridge, A., Splett, P., Singh, R. H.
|
|
<strong>Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): an evidence- and consensus-based approach.</strong>
|
|
Molec. Genet. Metab. 131: 23-37, 2020.
|
|
|
|
|
|
[PubMed: 33093005]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2020.10.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamaguchi, S., Indo, Y., Coates, P. M., Hashimoto, T., Tanaka, K.
|
|
<strong>Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency.</strong>
|
|
Pediat. Res. 34: 111-113, 1993.
|
|
|
|
|
|
[PubMed: 8356011]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-199307000-00025]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 11/17/2021<br>Hilary J. Vernon - updated : 06/14/2021<br>Hilary J. Vernon - updated : 04/15/2021<br>Ada Hamosh - updated : 12/08/2016<br>Ada Hamosh - updated : 1/20/2015<br>Cassandra L. Kniffin - updated : 12/4/2007<br>Victor A. McKusick - updated : 11/29/2007<br>Cassandra L. Kniffin - reorganized : 9/22/2005<br>Cassandra L. Kniffin - updated : 9/14/2005<br>Patricia A. Hartz - updated : 12/29/2003<br>George E. Tiller - updated : 2/7/2002<br>Victor A. McKusick - updated : 9/26/2001<br>Ada Hamosh - updated : 8/29/2001<br>Ada Hamosh - updated : 4/23/2001<br>Paul Brennan - updated : 7/3/2000<br>Victor A. McKusick - updated : 2/19/1999<br>Orest Hurko - updated : 11/6/1998<br>Victor A. McKusick - updated : 10/1/1998<br>Victor A. McKusick - updated : 12/2/1997<br>Moyra Smith - updated : 5/4/1996
|
|
</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 : 5/27/1993
|
|
</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 : 09/12/2022<br>carol : 11/17/2021<br>carol : 06/14/2021<br>joanna : 05/17/2021<br>carol : 04/15/2021<br>carol : 10/19/2017<br>alopez : 12/08/2016<br>carol : 09/07/2016<br>carol : 07/09/2016<br>alopez : 1/20/2015<br>carol : 4/27/2011<br>carol : 4/22/2011<br>wwang : 12/7/2007<br>ckniffin : 12/4/2007<br>alopez : 11/30/2007<br>alopez : 11/29/2007<br>alopez : 11/29/2007<br>carol : 9/22/2005<br>ckniffin : 9/14/2005<br>carol : 3/17/2004<br>tkritzer : 3/11/2004<br>tkritzer : 3/10/2004<br>carol : 12/29/2003<br>ckniffin : 6/13/2002<br>carol : 4/30/2002<br>cwells : 2/18/2002<br>cwells : 2/7/2002<br>carol : 10/4/2001<br>mcapotos : 10/1/2001<br>terry : 9/26/2001<br>cwells : 9/14/2001<br>cwells : 9/14/2001<br>cwells : 9/4/2001<br>terry : 8/29/2001<br>cwells : 5/22/2001<br>cwells : 5/9/2001<br>cwells : 5/7/2001<br>terry : 4/23/2001<br>alopez : 7/3/2000<br>mcapotos : 6/5/2000<br>mcapotos : 5/26/2000<br>carol : 5/22/2000<br>terry : 5/22/2000<br>terry : 6/9/1999<br>terry : 2/19/1999<br>carol : 11/25/1998<br>terry : 11/6/1998<br>carol : 10/5/1998<br>terry : 10/1/1998<br>terry : 6/4/1998<br>alopez : 12/15/1997<br>alopez : 12/15/1997<br>dholmes : 12/4/1997<br>carol : 7/13/1996<br>mark : 5/31/1996<br>mark : 5/31/1996<br>mark : 5/31/1996<br>carol : 5/22/1996<br>mark : 5/6/1996<br>carol : 5/4/1996<br>mark : 4/23/1996<br>mark : 1/25/1996<br>terry : 1/23/1996<br>mark : 12/6/1995<br>mark : 12/6/1995<br>mark : 8/30/1995<br>jason : 6/27/1994<br>mimadm : 3/11/1994<br>carol : 5/27/1993
|
|
</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>
|
|
|
|
|