5488 lines
525 KiB
Text
5488 lines
525 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
|
|
|
|
- #176000 - PORPHYRIA, ACUTE INTERMITTENT; AIP
|
|
|
|
|
|
- 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=176000"><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">#176000</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/176000"><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="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#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="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=PORPHYRIA, ACUTE INTERMITTENT" 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=11302&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/NBK1193/" 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/187" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=176000[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79276" 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:3890" 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/176000" 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/results?search_type=advanced&omia_id=000815,001493" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</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:176000" 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> 234422006, 276263005, 84816006<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 79276<br />
|
|
|
|
|
|
<strong>DO:</strong> 3890<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>
|
|
176000
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PORPHYRIA, ACUTE INTERMITTENT; AIP
|
|
|
|
</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">
|
|
PORPHYRIA, SWEDISH TYPE<br />
|
|
PORPHOBILINOGEN DEAMINASE DEFICIENCY<br />
|
|
PBGD DEFICIENCY<br />
|
|
UROPORPHYRINOGEN SYNTHASE DEFICIENCY<br />
|
|
UPS DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
PORPHYRIA, ACUTE INTERMITTENT, NONERYTHROID VARIANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
PORPHYRIA, CHESTER TYPE, INCLUDED; PORC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/1004?start=-3&limit=10&highlight=1004">
|
|
11q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Porphyria, acute intermittent
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/176000"> 176000 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
HMBS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609806"> 609806 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/1004?start=-3&limit=10&highlight=1004">
|
|
11q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Porphyria, acute intermittent, nonerythroid variant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/176000"> 176000 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
HMBS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609806"> 609806 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/176000" 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/176000" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/176000" 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 dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</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">
|
|
|
|
- Tachycardia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86651002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86651002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3424008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3424008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R00.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/785.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">785.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3827868&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3827868</a>, <a href="https://bioportal.bioontology.org/search?q=C0039231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Vascular </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypertension <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38341003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38341003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/401-405.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">401-405.99</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/997.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">997.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020538</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000822" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000822</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000822" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000822</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>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Lung </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Respiratory paralysis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035232&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035232</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002203" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002203</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002203" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002203</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nausea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422587007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422587007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027497&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027497</a>, <a href="https://bioportal.bioontology.org/search?q=C4255480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4255480</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002018</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002018</a>]</span><br /> -
|
|
Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br /> -
|
|
Diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267060006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267060006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62315008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R19.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R19.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011991</a>, <a href="https://bioportal.bioontology.org/search?q=C2169706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2169706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span><br /> -
|
|
Abdominal pain <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/21522001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">21522001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R10.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R10.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/789.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0000737&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0000737</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002027</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002027</a>]</span><br /> -
|
|
Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
|
|
Paralytic ileus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55525008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55525008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K56.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K56.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/560.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">560.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030446</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002590" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002590</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002590" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002590</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Bladder </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Urinary retention <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/130951007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">130951007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267064002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267064002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/449491000124101" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">449491000124101</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1251594002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1251594002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R33" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R33</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R33.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R33.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.20</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/788.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5700171&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5700171</a>, <a href="https://bioportal.bioontology.org/search?q=C0080274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0080274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000016" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000016</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000016" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000016</a>]</span><br /> -
|
|
Dysuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/49650001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">49650001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R30.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R30.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R30.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R30.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013428</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100518</a>]</span><br /> -
|
|
Urinary incontinence <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165232002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165232002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R32" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R32</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/788.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042024&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042024</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Acute episodes of neuropathic symptoms <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867971&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867971</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003489" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003489</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003489" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003489</a>]</span><br /> -
|
|
Paraesthesias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91019004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91019004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030554&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030554</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003401" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003401</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
|
Psychotic episodes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338614&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338614</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000725</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000725</a>]</span><br /> -
|
|
Depression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78667006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78667006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35489007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35489007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366979004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366979004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255339005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255339005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F34.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F34.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F32.A" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F32.A</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F33.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F33.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0812393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0812393</a>, <a href="https://bioportal.bioontology.org/search?q=C0011581&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011581</a>, <a href="https://bioportal.bioontology.org/search?q=C0460137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0460137</a>, <a href="https://bioportal.bioontology.org/search?q=C1579931&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1579931</a>, <a href="https://bioportal.bioontology.org/search?q=C0344315&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344315</a>, <a href="https://bioportal.bioontology.org/search?q=C4085311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4085311</a>, <a href="https://bioportal.bioontology.org/search?q=C0011570&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011570</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</a>]</span><br /> -
|
|
Anxiety <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48694002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48694002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197480006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197480006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F41.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F41.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003469&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003469</a>, <a href="https://bioportal.bioontology.org/search?q=C0003467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003467</a>, <a href="https://bioportal.bioontology.org/search?q=C0860603&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0860603</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000739" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000739</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000739" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000739</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Acute episodes of neuropathic symptoms <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867971&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867971</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003489" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003489</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003489" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003489</a>]</span><br /> -
|
|
Paralysis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44695005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44695005</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/344.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">344.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0522224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0522224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003470</a>]</span><br /> -
|
|
Motor, sensory, or autonomic neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867972</a>]</span><br /> -
|
|
Weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13791008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13791008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.81</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714552</a>, <a href="https://bioportal.bioontology.org/search?q=C0004093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025406</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025406</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Syndrome of inappropriate antidiuretic hormone (SIADH) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55004003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55004003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E22.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E22.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0021141&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021141</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031218</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased incidence of hepatocellular carcinoma <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867955&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867955</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</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">
|
|
|
|
- Erythrocyte porphobilinogen (PBG) deaminase deficiency (exception: type II AIP) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867973&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867973</a>]</span><br /> -
|
|
Increased urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) during acute attacks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867974&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867974</a>]</span><br /> -
|
|
Urine occasionally port-wine in color secondary to porphobilinogen <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867975&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867975</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">
|
|
|
|
- Acute attacks rarely occur before puberty<br /> -
|
|
Attacks precipitated by drugs (e.g. barbiturates, sulfonamides), alcohol, infection, starvation, and hormonal changes<br /> -
|
|
Attacks more common in women<br /> -
|
|
Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span><br /> -
|
|
Ninety percent of patients with PBG deaminase deficiency are clinically unaffected<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 hydroxymethylbilane synthase gene (HMBS, <a href="/entry/609806#0001">609806.0001</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 of evidence that acute intermittent porphyria (AIP) is caused by heterozygous mutation in the gene encoding hydroxymethylbilane synthase (HMBS; <a href="/entry/609806">609806</a>), also referred to as porphobilinogen deaminase (PBGD), on chromosome 11q23.</p><p>Biallelic mutation in the HMBS gene causes porphyria-related leukoencephalopathy (LENCEP; <a href="/entry/620711">620711</a>) and porphyria-related encephalopathy (ENCEP; <a href="/entry/620704">620704</a>), both of which are autosomal recessive disorders with persistent and progressive neurologic features.</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>Porphyrias are inherited defects in the biosynthesis of heme. Acute intermittent porphyria (AIP), the most common form of porphyria, is an autosomal dominant disorder characterized by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances. The disorder is notably incompletely penetrant: fewer than 10% of heterozygous mutation carriers actually develop acute porphyric attacks. Acute attacks rarely occur before puberty; they may be precipitated by porphyrinogenic drugs such as barbiturates and sulfonamides (for list, see <a href="#66" class="mim-tip-reference" title="Tschudy, D. P., Valsamis, M., Magnussen, C. R. <strong>Acute intermittent porphyria: clinical and selected research aspects.</strong> Ann. Intern. Med. 83: 851-864, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1106284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1106284</a>] [<a href="https://doi.org/10.7326/0003-4819-83-6-851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1106284">Tschudy et al., 1975</a>), some of which are known to induce the earlier rate-controlling step in heme synthesis, delta-aminolevulinic acid (ALA) synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women. The precipitants cause increased ALAS1 (<a href="/entry/125290">125290</a>) activity and increased levels of the porphyrin precursors ALA and PBG. The half-normal hepatic HMBS activity in heterozygous AIP patients is insufficient to prevent pathologic accumulation of these precursors, which are most likely responsible for the symptoms (<a href="#45" class="mim-tip-reference" title="Petrides, P. E. <strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong> Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10343207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10343207</a>] [<a href="https://doi.org/10.1159/000029859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10343207">Petrides, 1998</a>; <a href="#59" class="mim-tip-reference" title="Solis, C., Martinez-Bermejo, A., Naidich, T. P., Kaufmann, W. E., Astrin, K. H., Bishop, D. F., Desnick, R. J. <strong>Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias.</strong> Arch. Neurol. 61: 1764-1770, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15534187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15534187</a>] [<a href="https://doi.org/10.1001/archneur.61.11.1764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15534187">Solis et al., 2004</a>; <a href="#22" class="mim-tip-reference" title="Kevelam, S. H., Neeleman, R. A., Waisfisz, Q., Friesema, E. C. H., Langendonk, J. G., van der Knaap, M. S. <strong>Acute intermittent porphyria-related leukoencephalopathy.</strong> Neurology 87: 1258-1265, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27558376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27558376</a>] [<a href="https://doi.org/10.1212/WNL.0000000000003129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27558376">Kevelam et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15534187+27558376+10343207+1106284" 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 the classic form of AIP, both the ubiquitous 'nonerythroid' housekeeping HMBS isoform and the 'erythroid' HMBS isoform are deficient. However, about 5% of families have the 'nonerythroid variant' of AIP, with a defect only in the ubiquitous nonerythroid HMBS isoform and normal levels of the erythroid HMBS isoform. Clinical characteristics in the 2 forms are identical; diagnostic methods based on the level of enzyme in erythrocytes are ineffective (<a href="#52" class="mim-tip-reference" title="Puy, H., Gross, U., Deybach, J. C., Robreau, A. M., Frank, M., Nordmann, Y., Doss, M. <strong>Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria.</strong> Hum. Genet. 103: 570-575, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9860299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9860299</a>] [<a href="https://doi.org/10.1007/s004390050871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9860299">Puy et al., 1998</a>; <a href="#45" class="mim-tip-reference" title="Petrides, P. E. <strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong> Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10343207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10343207</a>] [<a href="https://doi.org/10.1159/000029859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10343207">Petrides, 1998</a>; <a href="#71" class="mim-tip-reference" title="Whatley, S. D., Roberts, A. G., Llewellyn, D. H., Bennett, C. P., Garrett, C., Elder, G. H. <strong>Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene.</strong> Hum. Genet. 107: 243-248, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11071386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11071386</a>] [<a href="https://doi.org/10.1007/s004390000356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11071386">Whatley et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11071386+9860299+10343207" 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>There are several other forms of porphyria: see porphyria cutanea tarda (<a href="/entry/176100">176100</a>), variegata porphyria (<a href="/entry/176200">176200</a>), coproporphyria (<a href="/entry/121300">121300</a>), acute hepatic porphyria (<a href="/entry/125270">125270</a>), and congenital erythropoietic porphyria (<a href="/entry/263700">263700</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>Acute intermittent porphyria is characterized clinically by acute episodes of a variety of gastrointestinal and neuropathic symptoms; between episodes, the patient is healthy. Abdominal pain is the most common symptom, sometimes with constipation and urinary retention; paraesthesias and paralysis also occur, and death may result from respiratory paralysis (<a href="#15" class="mim-tip-reference" title="Goldberg, A. <strong>Acute intermittent porphyria.</strong> Quart. J. Med. 28: 183-209, 1959.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13658350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13658350</a>]" pmid="13658350">Goldberg, 1959</a>; <a href="#62" class="mim-tip-reference" title="Stein, J. A., Tschudy, D. P. <strong>Acute intermittent porphyria: a clinical and biochemical study of 46 patients.</strong> Medicine 49: 1-16, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4907358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4907358</a>]" pmid="4907358">Stein and Tschudy, 1970</a>; <a href="#6" class="mim-tip-reference" title="Becker, D. M., Kramer, S. <strong>The neurological manifestations of porphyria: a review.</strong> Medicine 56: 411-423, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/329053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">329053</a>] [<a href="https://doi.org/10.1097/00005792-197709000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="329053">Becker and Kramer, 1977</a>). Many other phenomena, including seizures, psychotic episodes, and hypertension, may occur in acute attacks. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13658350+329053+4907358" 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>From a survey of AIP cases in the west of Scotland, <a href="#25" class="mim-tip-reference" title="Laiwah, A. A. C. Y., Mactier, R., McColl, K. E. L., Moore, M. R., Goldberg, A. <strong>Early-onset chronic renal failure as a complication of acute intermittent porphyria.</strong> Quart. J. Med. 52: 92-98, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6878621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6878621</a>]" pmid="6878621">Laiwah et al. (1983)</a> observed an association with early-onset chronic renal failure. Porphyria-induced hypertension was considered the most likely causal factor, but enhanced susceptibility to analgesic nephropathy and nephrotoxic effects of porphyrins and their precursors were mentioned as possibilities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6878621" 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>Marsden and Rees (2014) measured urine ALA, PBG, and total urine porphyrin (TUP) excretion in 20 patients with AIP following an attack of acute porphyria for 3 months to 23 years after their last documented acute attack. Urinary concentrations of all metabolites remained elevated for many years. The urinary half-life of TUP was 5.3 years, ALA 7.7 years, and PBG 10.6 years. Even after 20 years, PBG concentrations remained elevated above the normal range. <a href="#34" class="mim-tip-reference" title="Marsden, J. T., Rees, D. C. <strong>Urinary excretion of porphyrins, porphobilinogen and delta-aminolaevulinic acid following an attack of acute intermittent porphyria.</strong> J. Clin. Path. 67: 60-65, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23908454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23908454</a>] [<a href="https://doi.org/10.1136/jclinpath-2012-201367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23908454">Marsden and Rees (2014)</a> concluded that whereas measurement of urine PBG is useful to diagnose the first attack of AIP, it is not helpful as a diagnostic tool in subsequent attacks. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23908454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R. <strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong> Lancet 326: 796-799, 1985. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864531</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)90793-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2864531">McColl et al. (1985)</a> identified a form of acute porphyria in a large family in Chester, U.K. Patients presented with attacks of neurovisceral dysfunction; none had cutaneous photosensitivity. Biochemically, the pattern of excretion of heme precursors varied between individuals. Some had a pattern of acute intermittent porphyria, others showed that of variegate porphyria, and some showed an intermediate pattern. A dual enzyme deficiency was found in peripheral blood cells; reduced activity was found in both PBGD, as in AIP, and protoporphyrinogen oxidase (PPOX; <a href="/entry/600923">600923</a>), as in variegate porphyria. <a href="#36" class="mim-tip-reference" title="McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R. <strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong> Lancet 326: 796-799, 1985. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864531</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)90793-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2864531">McColl et al. (1985)</a> initially thought that this was a new form of porphyria. The finding of <a href="#48" class="mim-tip-reference" title="Poblete-Gutierrez, P., Wiederholt, T., Martinez-Mir, A., Merk, H. F., Connor, J. M., Christiano, A. M., Frank, J. <strong>Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene.</strong> Physiol. Res. 55 (Suppl. 2): S137-S144, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17298217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17298217</a>] [<a href="https://doi.org/10.33549/physiolres.930000.55.S2.137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17298217">Poblete-Gutierrez et al. (2006)</a> of a mutation in the HMBS gene in affected individuals (see MOLECULAR GENETICS) confirmed that Chester type porphyria is a variant of AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17298217+2864531" 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>The essential biochemical finding in acute attacks of AIP is increased urinary excretion of the HMBS precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG); this is the basis for the Watson-Schwartz test (<a href="#70" class="mim-tip-reference" title="Watson, C. J., Bossenmaier, I. <strong>Present status of the Ehrlich aldehyde reaction for urinary porphobilinogen.</strong> JAMA 190: 501-504, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14198005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14198005</a>] [<a href="https://doi.org/10.1001/jama.1964.03070190021004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14198005">Watson and Bossenmaier, 1964</a>). Many latent AIP subjects never have acute attacks, but some intermittently excrete excess porphyrin precursors in urine without having symptoms. Porphyrins may be formed in the urine from the precursors (<a href="#69" class="mim-tip-reference" title="Waldenstrom, J. <strong>Studies on the incidence and heredity of acute porphyria in Sweden.</strong> Acta Genet. Statist. Med. 6: 122-131, 1956.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13354248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13354248</a>]" pmid="13354248">Waldenstrom, 1956</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14198005+13354248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Anderson, K. E., Bradlow, H. L., Sassa, S., Kappas, A. <strong>Studies in porphyria. VIII. Relationship of the 5-alpha-reductive metabolism of steroid hormone to clinical expression of the genetic defect in acute intermittent porphyria.</strong> Am. J. Med. 66: 644-650, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/433969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">433969</a>] [<a href="https://doi.org/10.1016/0002-9343(79)91176-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="433969">Anderson et al. (1979)</a> described abnormalities in steroid metabolism in AIP patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=433969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 22 unrelated families with AIP, <a href="#3" class="mim-tip-reference" title="Anderson, P. M., Reddy, R. M., Anderson, K. E., Desnick, R. J. <strong>Characterization of the porphobilinogen deaminase deficiency in acute intermittent porphyria: immunologic evidence for heterogeneity of the genetic defect.</strong> J. Clin. Invest. 68: 1-12, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7251856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7251856</a>] [<a href="https://doi.org/10.1172/jci110223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7251856">Anderson et al. (1981)</a> found differences in the pattern of the 5 stable enzyme-substrate intermediates (A, B, C, D, E) of PBG-deaminase separated by anion-exchange chromatography of erythrocyte lysates. In most patients, the elution profile was similar to the normal with each intermediate reduced about 50%. Some heterozygotes had a second profile in which the C intermediate had disproportionately higher activity than the A or B intermediates; this pattern was observed during an acute attack, suggesting that induction of the enzyme depends on substrate concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7251856" 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="#67" class="mim-tip-reference" title="Verma, A., Nye, J. S., Snyder, S. H. <strong>Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor.</strong> Proc. Nat. Acad. Sci. 84: 2256-2260, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031675</a>] [<a href="https://doi.org/10.1073/pnas.84.8.2256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3031675">Verma et al. (1987)</a> found that porphyrins are endogenous ligands for a 'peripheral type' of benzodiazepine receptor, which is selectively associated with the outer mitochondrial membrane. The anxiolytic effects of benzodiazepines are mediated by a 'central' benzodiazepine receptor, located primarily in the brain. The findings may have relevance to the neuropsychiatric aspects of AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3031675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Mustajoki, P., Desnick, R. J. <strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong> Brit. Med. J. 291: 505-509, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928029</a>] [<a href="https://doi.org/10.1136/bmj.291.6494.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3928029">Mustajoki and Desnick (1985)</a> used biochemical and immunologic techniques to characterize 4 mutant types of porphobilinogen deaminase in 68 AIP patients from 33 unrelated families in Finland. About 80% of the mutant enzymes were cross-reactive immunologic material (CRM)-negative and fell into 2 types: those in which PBGD levels and enzyme activity were half-normal in all tissues, and a large kindred with normal erythrocyte PBGD levels. The remainder of the families had CRM-positive mutations, including an unusual group that had increased levels of immunoreactive, non-catalytic enzyme. <a href="#41" class="mim-tip-reference" title="Mustajoki, P., Desnick, R. J. <strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong> Brit. Med. J. 291: 505-509, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928029</a>] [<a href="https://doi.org/10.1136/bmj.291.6494.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3928029">Mustajoki and Desnick (1985)</a> suggested that the CRM-positive patients of the second type have milder disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3928029" 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="#10" class="mim-tip-reference" title="Desnick, R. J., Ostasiewicz, L. T., Tishler, P. A., Mustajoki, P. <strong>Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. Demonstration of noncatalytic enzyme intermediates stabilized by bound substrate.</strong> J. Clin. Invest. 76: 865-874, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3897290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3897290</a>] [<a href="https://doi.org/10.1172/JCI112044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3897290">Desnick et al. (1985)</a> further characterized the 4 classes of mutations in AIP by studying 165 AIP heterozygotes from 92 unrelated families. The majority of patients had CRM-negative mutations with half-normal PBGD activity; these were designated 'CRM-negative type 1.' In 3 families, designated 'CRM-negative type 2,' symptomatic patients had increased urinary delta-ALA and PBG with normal levels of erythrocyte PBGD activity. Eleven families had CRM-positive, noncatalytic PBGD. Of these, a subset of patients had increased levels of noncatalytic PBGD with increased levels of substrate-bound intermediates, suggestive of increased binding affinity. The findings indicated allelic heterogeneity for mutations in the PBGD gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3897290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Nonerythroid Variant of AIP</em></strong></p><p>
|
|
<a href="#42" class="mim-tip-reference" title="Mustajoki, P. <strong>Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria.</strong> Ann. Intern. Med. 95: 162-166, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258864</a>] [<a href="https://doi.org/10.7326/0003-4819-95-2-162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7258864">Mustajoki (1981)</a> reported a large kindred in which 10 members had AIP with normal erythrocyte PBG-deaminase activity. This form is referred to as the 'nonerythroid variant' of AIP. Forty-nine other Finnish patients with AIP who were unrelated to this kindred had the usual low activity of PBG-deaminase. <a href="#42" class="mim-tip-reference" title="Mustajoki, P. <strong>Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria.</strong> Ann. Intern. Med. 95: 162-166, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258864</a>] [<a href="https://doi.org/10.7326/0003-4819-95-2-162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7258864">Mustajoki (1981)</a> suggested that the large kindred represented a variant form of AIP in which the enzyme defect was not expressed in erythrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7258864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of affected members from 22 unrelated families with AIP, <a href="#3" class="mim-tip-reference" title="Anderson, P. M., Reddy, R. M., Anderson, K. E., Desnick, R. J. <strong>Characterization of the porphobilinogen deaminase deficiency in acute intermittent porphyria: immunologic evidence for heterogeneity of the genetic defect.</strong> J. Clin. Invest. 68: 1-12, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7251856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7251856</a>] [<a href="https://doi.org/10.1172/jci110223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7251856">Anderson et al. (1981)</a> demonstrated heterogeneity of the erythrocyte porphobilinogen deaminase defect. Although affected members from 21 families had absent CRM to the PBGD protein, all 7 AIP heterozygotes from 1 family of Basque origin had positive CRM results detected in red cell lysates. Further studies showed that this family had a noncatalytic, immunoreactive protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7251856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Mustajoki, P., Desnick, R. J. <strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong> Brit. Med. J. 291: 505-509, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928029</a>] [<a href="https://doi.org/10.1136/bmj.291.6494.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3928029">Mustajoki and Desnick (1985)</a> and <a href="#10" class="mim-tip-reference" title="Desnick, R. J., Ostasiewicz, L. T., Tishler, P. A., Mustajoki, P. <strong>Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. Demonstration of noncatalytic enzyme intermediates stabilized by bound substrate.</strong> J. Clin. Invest. 76: 865-874, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3897290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3897290</a>] [<a href="https://doi.org/10.1172/JCI112044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3897290">Desnick et al. (1985)</a> also identified patients with AIP who had normal levels and activity of erythrocyte PBG-deaminase. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3928029+3897290" 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>Acute intermittent porphyria, and several other genetic porphyrias, are unusual among enzyme deficiency states in that symptoms are manifest in the heterozygous state, consistent with autosomal dominant inheritance (<a href="#38" class="mim-tip-reference" title="Meyer, U. A., Schmid, R. <strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong> New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220."None>Meyer and Schmid, 1978</a>).</p><p><a href="#12" class="mim-tip-reference" title="Doss, M. O. <strong>Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies.</strong> Clin. Genet. 35: 146-151, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2721023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2721023</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1989.tb02920.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2721023">Doss (1989)</a> described 4 unrelated individuals with coexistent AIP, caused by deficiency of PBGD, and porphyria cutanea tarda (<a href="/entry/176100">176100</a>), caused by deficiency of uroporphyrinogen decarboxylase (UROD; <a href="/entry/613521">613521</a>). The patients manifested clinical courses of both diseases. Family studies showed that in 1 case the dually affected father transmitted both deficiencies to 1 son and only 1 deficiency to a second son. The findings were consistent with the nonlinkage and nonallelism of the 2 genes underlying the disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2721023" 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="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#41" class="mim-tip-reference" title="Mustajoki, P., Desnick, R. J. <strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong> Brit. Med. J. 291: 505-509, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928029</a>] [<a href="https://doi.org/10.1136/bmj.291.6494.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3928029">Mustajoki and Desnick (1985)</a> provided a useful illustration of the putative mutation sites in the heme-synthesis pathway in each of 6 forms of porphyria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3928029" 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 patients with AIP, porphobilinogen deaminase activity reduced to approximately half the normal level was demonstrated first in liver (<a href="#63" class="mim-tip-reference" title="Strand, L. J., Felsher, B. F., Redeker, A. G., Marver, H. S. <strong>Heme biosynthesis in intermittent acute porphyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity.</strong> Proc. Nat. Acad. Sci. 67: 1315-1320, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5274461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5274461</a>] [<a href="https://doi.org/10.1073/pnas.67.3.1315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5274461">Strand et al., 1970</a>), and subsequently in cultured fibroblasts and red blood cells (<a href="#39" class="mim-tip-reference" title="Meyer, U. A., Strand, L. J., Doss, M., Rees, A. C., Marver, H. S. <strong>Intermittent acute porphyria--demonstration of a genetic defect in porphobilinogen metabolism.</strong> New Eng. J. Med. 286: 1277-1282, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5024458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5024458</a>] [<a href="https://doi.org/10.1056/NEJM197206152862401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5024458">Meyer et al., 1972</a>; <a href="#64" class="mim-tip-reference" title="Strand, L. J., Meyer, U. A., Felsher, B. F., Redeker, A. G., Marver, H. S. <strong>Decreased red cell uroporphyrinogen I synthetase activity in intermittent acute porphyria.</strong> J. Clin. Invest. 51: 2530-2536, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5056653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5056653</a>] [<a href="https://doi.org/10.1172/JCI107068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5056653">Strand et al., 1972</a>; <a href="#54" class="mim-tip-reference" title="Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A. <strong>A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease.</strong> Proc. Nat. Acad. Sci. 71: 732-736, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4522787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4522787</a>] [<a href="https://doi.org/10.1073/pnas.71.3.732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4522787">Sassa et al., 1974</a>; <a href="#24" class="mim-tip-reference" title="Kreimer-Birnbaum, M. <strong>Uroporphyrinogen synthase in human blood: developmental studies.</strong> Life Sci. 17: 1473-1478, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1207410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1207410</a>] [<a href="https://doi.org/10.1016/0024-3205(75)90169-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1207410">Kreimer-Birnbaum, 1975</a>). In family studies, most individuals can be characterized as having either clearly normal or 50% decreased levels of PBGD activity, but intermediate values are sometimes found (<a href="#54" class="mim-tip-reference" title="Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A. <strong>A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease.</strong> Proc. Nat. Acad. Sci. 71: 732-736, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4522787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4522787</a>] [<a href="https://doi.org/10.1073/pnas.71.3.732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4522787">Sassa et al., 1974</a>; <a href="#5" class="mim-tip-reference" title="Astrup, E. G. <strong>Family studies on the activity of uroporphyrinogen I synthase in diagnosis of acute intermittent porphyria.</strong> Clin. Sci. Molec. Med. 54: 251-256, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/630801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">630801</a>] [<a href="https://doi.org/10.1042/cs0540251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="630801">Astrup, 1978</a>; <a href="#23" class="mim-tip-reference" title="Kreimer-Birnbaum, M., Bannerman, R. M., El Khatib, M., Franco-Saenz, R. <strong>Afro-Americans and acute intermittent porphyria.</strong> Int. J. Biochem. 12: 795-799, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7450135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7450135</a>] [<a href="https://doi.org/10.1016/0020-711x(80)90165-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7450135">Kreimer-Birnbaum et al., 1980</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5056653+5024458+630801+5274461+7450135+4522787+1207410" 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="Goldberg, A. <strong>Molecular genetics of acute intermittent porphyria. (Editorial)</strong> Brit. Med. J. 291: 499-500, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928028</a>] [<a href="https://doi.org/10.1136/bmj.291.6494.499-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3928028">Goldberg (1985)</a> wrote that allelic heterogeneity in AIP may be a factor 'among others, such as drugs, diet, and endogenous hormones, which determine whether the latent state in one patient may continue without incident or, in another, may be shattered by a painful and crippling attack.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3928028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In 33 unrelated patients with acute intermittent porphyria, <a href="#32" class="mim-tip-reference" title="Llewellyn, D. H., Elder, G. H., Kalsheker, N. A., Marsh, O. W. M., Harrison, P. R., Grandchamp, B., Picat, C., Nordmann, Y., Romeo, P. H., Goossens, M. <strong>DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria.</strong> Lancet 334: 706-708, 1987. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2888941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2888941</a>] [<a href="https://doi.org/10.1016/s0140-6736(87)91073-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2888941">Llewellyn et al. (1987)</a> found linkage to a common 2-allele MspI RFLP of the PBGD gene (maximum lod score of 3.14 with no recombinants). In 30 patients, no cross-reacting immunologic material was produced by the mutant allele. A major gene deletion was excluded as the cause of the CRM-negative mutation in 18 heterozygous families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2888941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By PCR, <a href="#29" class="mim-tip-reference" title="Lee, J.-S., Lindsten, J., Anvret, M. <strong>Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction.</strong> Hum. Genet. 84: 241-243, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2303246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2303246</a>] [<a href="https://doi.org/10.1007/BF00200567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2303246">Lee et al. (1990)</a> amplified polymorphic sites in the PBGD gene that could be used for linkage analysis in AIP families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2303246" 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="#58" class="mim-tip-reference" title="Scobie, G. A., Urquhart, A. J., Elder, G. H., Kalsheker, N. A., Llewellyn, D. H., Smyth, J., Harrison, P. R. <strong>Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene.</strong> Hum. Genet. 85: 157-159, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973402</a>] [<a href="https://doi.org/10.1007/BF00193188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1973402">Scobie et al. (1990)</a> identified three 2-allele RFLPs in the PBGD gene, each with allele frequencies close to 0.50. Marked linkage disequilibrium limited the number of observed haplotypes to 4, of which 1 was uncommon. No common haplotype was observed among 47 unrelated AIP patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 Finnish families, each with a different subtype of AIP (CRM-negative with low red cell enzyme activity; CRM-positive with low enzyme activity; CRM-negative with normal enzyme activity), <a href="#21" class="mim-tip-reference" title="Kauppinen, R., Peltonen, L., Palotie, A., Mustajoki, P. <strong>RFLP analysis of three different types of acute intermittent porphyria.</strong> Hum. Genet. 85: 160-164, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973403</a>] [<a href="https://doi.org/10.1007/BF00193189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1973403">Kauppinen et al. (1990)</a> found evidence of tight linkage to PBGD RFLPs. Among 62 family members tested, 30 had a familial disease-associated haplotype; in 5 of them, conventional tests for AIP were normal, and in 1, uncertain. The authors concluded that RFLP analysis could be used to detect gene carriers and to help in the diagnosis of persons with uncertain results in other tests. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973403" 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 the family from Chester, U.K. reported by <a href="#36" class="mim-tip-reference" title="McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R. <strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong> Lancet 326: 796-799, 1985. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864531</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)90793-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2864531">McColl et al. (1985)</a> Norton et al. (<a href="#44" class="mim-tip-reference" title="Norton, B., Lanyon, W. G., Moore, M. R., Youngs, G. R., Tomlinson, J. E. M., Aitken, D. A., Connor, J. M. <strong>Evidence for a second genetic locus for porphyrin metabolism on chromosome 11q. (Abstract)</strong> J. Med. Genet. 28: 551-552, 1991."None>1991</a>, <a href="#43" class="mim-tip-reference" title="Norton, B., Lanyon, W. G., Moore, M. R., Porteous, M., Youngs, G. R., Connor, J. M. <strong>Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism.</strong> Hum. Genet. 91: 576-578, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8340112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8340112</a>] [<a href="https://doi.org/10.1007/BF00205083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8340112">1993</a>) identified a multipoint maximum lod score of 7.33 at a distance less than 1 cM proximal to D11S351. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8340112+2864531" 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 a large Dutch family with the nonerythroid variant of AIP, <a href="#19" class="mim-tip-reference" title="Grandchamp, B., Picat, C., Mignotte, V., Wilson, J. H. P., te Velde, K., Sandkuyl, L., Romeo, P. H., Goossens, M., Nordmann, Y. <strong>Tissue-specific splicing mutation in acute intermittent porphyria.</strong> Proc. Nat. Acad. Sci. 86: 661-664, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2563167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2563167</a>] [<a href="https://doi.org/10.1073/pnas.86.2.661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2563167">Grandchamp et al. (1989)</a> identified a heterozygous splice site mutation in intron 1 of the HMBS gene (<a href="/entry/609806#0001">609806.0001</a>). The mutation interrupted the sequence coding for the nonerythroid isoform of PBGD; thus, expression of the erythroid isoform was unaffected. In a patient with CRM-positive AIP, <a href="#18" class="mim-tip-reference" title="Grandchamp, B., Picat, C., de Rooij, F., Beaumont, C., Wilson, P., Deybach, J. C., Nordmann, Y. <strong>A point mutation G-to-A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria.</strong> Nucleic Acids Res. 17: 6637-6649, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2789372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2789372</a>] [<a href="https://doi.org/10.1093/nar/17.16.6637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2789372">Grandchamp et al. (1989)</a> identified a mutation in the HMBS gene, resulting in the skipping of exon 12 (<a href="/entry/609806#0002">609806.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2789372+2563167" 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 affected members of 11 different families with either CRM-negative or CRM-positive AIP, <a href="#17" class="mim-tip-reference" title="Grandchamp, B., Delfau, M. H., Picat, C., de Rooij, F. W. M., Nordmann, Y. <strong>Heterogeneity of the molecular defects in acute intermittent porphyria. (Abstract)</strong> Am. J. Hum. Genet. 47 (suppl.): A156 only, 1990."None>Grandchamp et al. (1990)</a> identified 7 different point mutations in the HMBS gene.</p><p><a href="#4" class="mim-tip-reference" title="Astrin, K. H., Desnick, R. J. <strong>Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene.</strong> Hum. Mutat. 4: 243-252, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7866402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7866402</a>] [<a href="https://doi.org/10.1002/humu.1380040403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7866402">Astrin and Desnick (1994)</a> reviewed the 26 mutations in the HMBS identified to that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7866402" 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="#50" class="mim-tip-reference" title="Puy, H., Deybach, J. C., Lamoril, J., Robreau, A. M., Da Silva, V., Gouya, L., Grandchamp, B., Nordmann, Y. <strong>Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.</strong> Am. J. Hum. Genet. 60: 1373-1383, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199558</a>] [<a href="https://doi.org/10.1086/515455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199558">Puy et al. (1997)</a> performed molecular analysis of the PBGD gene by denaturing gradient gel electrophoresis followed by direct sequencing in 405 subjects from 121 unrelated French-Caucasian AIP families. PBGD mutations were identified in 109 families, but only 78 were of different type, and each of these had a prevalence rate of less than 5%. Among these mutations, 33 had not previously been published. Sixty percent of the 78 mutations were located in 3 exons (exons 10, 12, and 14); 44% were missense, 18% were splice defect, 19% were frameshift, and 16% were nonsense. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199558" 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="#72" class="mim-tip-reference" title="Whatley, S. D., Woolf, J. R., Elder, G. H. <strong>Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations.</strong> Hum. Genet. 104: 505-510, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10453740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10453740</a>] [<a href="https://doi.org/10.1007/s004390050995" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10453740">Whatley et al. (1999)</a> reported a prospective comparison of direct automated sequencing of cDNA (in 29 patients) or genomic DNA (in 28 patients) to identify HMBS mutations in 57 patients referred consecutively for mutation analysis; 39 different mutations were identified in 54 patients. The sensitivity of the cDNA and genomic DNA methods was 69% and 95%, respectively, indicating that analysis of genomic DNA provides a higher mutation detection rate. The mutations included 6 missense, 8 splice defects, 10 frameshifts, and 1 nonsense; 25 had not previously been reported. The results defined the extent of allelic heterogeneity and the types (41% missense, 59% truncating) and distribution (35% in exons 10, 12, and 14) of HMBS mutations for AIP in the United Kingdom. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10453740" 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 affected members of the original family reported by <a href="#36" class="mim-tip-reference" title="McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R. <strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong> Lancet 326: 796-799, 1985. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864531</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)90793-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2864531">McColl et al. (1985)</a>, <a href="#48" class="mim-tip-reference" title="Poblete-Gutierrez, P., Wiederholt, T., Martinez-Mir, A., Merk, H. F., Connor, J. M., Christiano, A. M., Frank, J. <strong>Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene.</strong> Physiol. Res. 55 (Suppl. 2): S137-S144, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17298217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17298217</a>] [<a href="https://doi.org/10.33549/physiolres.930000.55.S2.137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17298217">Poblete-Gutierrez et al. (2006)</a> identified a heterozygous truncating mutation in the HMBS gene (<a href="/entry/609806#0046">609806.0046</a>). No mutations were found in the PPOX gene. These findings confirmed that Chester type porphyria is a variant of AIP. <a href="#48" class="mim-tip-reference" title="Poblete-Gutierrez, P., Wiederholt, T., Martinez-Mir, A., Merk, H. F., Connor, J. M., Christiano, A. M., Frank, J. <strong>Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene.</strong> Physiol. Res. 55 (Suppl. 2): S137-S144, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17298217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17298217</a>] [<a href="https://doi.org/10.33549/physiolres.930000.55.S2.137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17298217">Poblete-Gutierrez et al. (2006)</a> suggested that the original biochemical studies indicating PPOX deficiency may have been erroneous or misinterpreted. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17298217+2864531" 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="#55" class="mim-tip-reference" title="Sassa, S., Solish, G., Levere, R. D., Kappas, A. <strong>Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait.</strong> J. Exp. Med. 142: 722-731, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1165472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1165472</a>] [<a href="https://doi.org/10.1084/jem.142.3.722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1165472">Sassa et al. (1975)</a> noted that the enzyme defect in AIP is expressed in cultured fibroblasts and amniotic cells, making prenatal diagnosis possible. The enzyme can be induced and the defect demonstrated in mitogen-stimulated lymphocytes (<a href="#56" class="mim-tip-reference" title="Sassa, S., Zalar, G. L., Kappas, A. <strong>Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.</strong> J. Clin. Invest. 61: 499-508, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/621286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">621286</a>] [<a href="https://doi.org/10.1172/JCI108961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="621286">Sassa et al., 1978</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=621286+1165472" 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="#50" class="mim-tip-reference" title="Puy, H., Deybach, J. C., Lamoril, J., Robreau, A. M., Da Silva, V., Gouya, L., Grandchamp, B., Nordmann, Y. <strong>Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.</strong> Am. J. Hum. Genet. 60: 1373-1383, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199558</a>] [<a href="https://doi.org/10.1086/515455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199558">Puy et al. (1997)</a> found that the standard PBGD enzymatic screening method for gene-carrier detection had 95% concordancy with the molecular-based diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199558" 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>Most acute attacks, if correctly recognized, settle with supportive treatment; dextrose infusion and high carbohydrate intake may be helpful (<a href="#62" class="mim-tip-reference" title="Stein, J. A., Tschudy, D. P. <strong>Acute intermittent porphyria: a clinical and biochemical study of 46 patients.</strong> Medicine 49: 1-16, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4907358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4907358</a>]" pmid="4907358">Stein and Tschudy, 1970</a>). Successful treatment by infusion of hematin, which is a specific feedback inhibitor of heme synthesis, has repeatedly been reported (<a href="#37" class="mim-tip-reference" title="McColl, K. E. L., Thompson, G. T., Moore, M. R., Goldberg, A. <strong>Haematin therapy and leucocyte gamma-aminolaevulinic-acid-synthase activity in prolonged attack of acute porphyria.</strong> Lancet 313: 133-134, 1979. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/84154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">84154</a>] [<a href="https://doi.org/10.1016/s0140-6736(79)90522-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="84154">McColl et al., 1979</a>; <a href="#26" class="mim-tip-reference" title="Lamon, J. M., Frykholm, B. C., Hess, R. A., Tschudy, D. P. <strong>Hematin therapy for acute porphyria.</strong> Medicine 58: 252-269, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/449661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">449661</a>] [<a href="https://doi.org/10.1097/00005792-197905000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="449661">Lamon et al., 1979</a>), but hematin is neither readily available nor very soluble and its use may carry a risk of renal damage (<a href="#11" class="mim-tip-reference" title="Dhar, G., Bossenmaier, I., Cardinal, R., Petryka, Z. J., Watson, C. J. <strong>Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission.</strong> Acta Med. Scand. 203: 437-443, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/665312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">665312</a>] [<a href="https://doi.org/10.1111/j.0954-6820.1978.tb14903.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="665312">Dhar et al., 1978</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=665312+4907358+84154+449661" 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="Goetsch, C. A., Bissell, D. M. <strong>Instability of hematin used in the treatment of acute hepatic porphyria.</strong> New Eng. J. Med. 315: 235-238, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3724815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3724815</a>] [<a href="https://doi.org/10.1056/NEJM198607243150406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3724815">Goetsch and Bissell (1986)</a> described a 22-year-old woman who had had more than 15 acute attacks requiring hospitalization. Hematin was the mainstay of the patient's therapy, eliciting a well-defined clinical and biochemical response after more than 200 infusions. On one occasion, however, the patient did not respond to a batch of hematin that, in retrospect, was found to have deteriorated. <a href="#14" class="mim-tip-reference" title="Goetsch, C. A., Bissell, D. M. <strong>Instability of hematin used in the treatment of acute hepatic porphyria.</strong> New Eng. J. Med. 315: 235-238, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3724815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3724815</a>] [<a href="https://doi.org/10.1056/NEJM198607243150406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3724815">Goetsch and Bissell (1986)</a> quantified the instability of hematin and showed that the decay product(s) is ineffective in regulating porphyrin production. The decayed material, furthermore, was found to have anticoagulant effects, thus explaining one of the complications of hematin therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3724815" 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>An experience reported by <a href="#2" class="mim-tip-reference" title="Anderson, K. E., Spitz, I. M., Sassa, S., Bardin, C. W., Kappas, A. <strong>Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone.</strong> New Eng. J. Med. 311: 643-645, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6433194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6433194</a>] [<a href="https://doi.org/10.1056/NEJM198409063111006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6433194">Anderson et al. (1984)</a> suggests that in women with premenstrual exacerbation of AIP, a long-acting agonist of luteinizing hormone-releasing hormone may be an effective preventive measure. <a href="#61" class="mim-tip-reference" title="Srugo, I., Said, E., Korman, S., Jaffe, M. <strong>Acute intermittent porphyria--an unusual cause of 'surgical' abdomen: response to propranolol therapy.</strong> Europ. J. Pediat. 146: 305-308, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3595653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3595653</a>] [<a href="https://doi.org/10.1007/BF00716482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3595653">Srugo et al. (1987)</a> described acute intermittent porphyria as the cause of 'surgical abdomen' in a 15-year-old boy. Because hypertension, tachycardia, and paralytic ileus were present, suggesting sympathetic overactivity, the beta-adrenergic blocking agent propranolol was administered in high doses with apparent dramatic improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3595653+6433194" 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 9 members of a German kindred in which the proband had nonerythroid variant of AIP resulting in a life-threatening coma, <a href="#45" class="mim-tip-reference" title="Petrides, P. E. <strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong> Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10343207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10343207</a>] [<a href="https://doi.org/10.1159/000029859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10343207">Petrides (1998)</a> identified a mutation in the HMBS gene (<a href="/entry/609806#0001">609806.0001</a>). The newly identified family members were informed of the disease and taught how to prevent porphyric attacks. They were also given medical alert information certificates. <a href="#45" class="mim-tip-reference" title="Petrides, P. E. <strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong> Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10343207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10343207</a>] [<a href="https://doi.org/10.1159/000029859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10343207">Petrides (1998)</a> emphasized the importance of identifying gene carriers as part of the clinical management of AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10343207" 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="#60" class="mim-tip-reference" title="Soonawalla, Z. F., Orug, T., Badminton, M. N., Elder, G. H., Rhodes, J. M., Bramhall, S. R., Elias, E. <strong>Liver transplantation as a cure for acute intermittent porphyria.</strong> Lancet 363: 705-706, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15001330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15001330</a>] [<a href="https://doi.org/10.1016/S0140-6736(04)15646-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15001330">Soonawalla et al. (2004)</a> reported a 19-year-old woman with severe AIP who underwent successful treatment with liver transplantation. After the transplant, concentrations of heme precursors in the patient's urine returned to normal and 1.5 years later, her quality of life was good. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15001330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Pischik, E., Kauppinen, R. <strong>An update of clinical management of acute intermittent porphyria.</strong> Appl. Clin. Genet. 8: 201-214, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26366103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26366103</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26366103[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/10.2147/TACG.S48605" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26366103">Pischik and Kauppinen (2015)</a> suggested the following clinical management of AIP. During an acute attack, they recommended treatment with heme preparation if the attack was severe or moderate; symptomatic treatment of autonomic dysfunctions, polyneuropathy, and encephalopathy; exclusion of precipitating factor; and adequate nutrition and fluid therapy. During remissions, they recommended exclusion of precipitating factors, including education of patients and family doctors; information about online drug lists; and mutation screening and education for family members. In patients with recurrent attacks, they recommended evaluation of lifestyle; evaluation of hormonal therapy in women; prophylactic heme therapy; and liver transplantation in patients with severe recurrent attacks. They noted that all AIP patients should be followed up for long-term complications including hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26366103" 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="#7" class="mim-tip-reference" title="Bissell, D. M., Anderson, K. E., Bonkovsky, H. L. <strong>Porphyria.</strong> New Eng. J. Med. 377: 862-872, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28854095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28854095</a>] [<a href="https://doi.org/10.1056/NEJMra1608634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28854095">Bissell et al. (2017)</a> reviewed the treatment of patients with AIP. The initial management includes reviewing medications that are considered to be risky for such patients and the administration of fluids (preferably 10% dextrose in 0.45% saline), antiemetic agents, analgesic agents, and, if indicated, antiseizure medications. Antiepileptic drugs must be especially carefully considered. Their Table 3 listed probably safe/possibly unsafe/unsafe medications; unsafe drugs included phenytoin, barbiturates of all type, valproic acid, carbamazepine, and primidone as well as oral contraceptives, progestins, carisoprodol, and spironolactone. The authors cited 2 online resources that provide detailed information on the use of drugs in this disorder. The only specific treatment for acute attacks is intravenous heme (Panhematin in the United States and Normosang in Europe). The authors noted that frequent courses of heme can result in hepatic iron buildup and injury due to iron overload. They cited alternatives to intravenous heme that were being developed and were in clinical trials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28854095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To determine whether chronic hemin administration contributes to the recurrence of acute attacks in AIP, <a href="#57" class="mim-tip-reference" title="Schmitt, C., Lenglet, H., Yu, A., Delaby, C., Benecke, A., Lefebvre, T., Letteron, P., Paradis, V., Wahlin, S., Sandberg, S., Harper, P., Sardh, E., and 16 others. <strong>Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.</strong> J. Intern. Med. 284: 78-91, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29498764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29498764</a>] [<a href="https://doi.org/10.1111/joim.12750" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29498764">Schmitt et al. (2018)</a> performed a follow-up study of 602 French symptomatic AIP patients, of whom 46 had recurrent AIP, who were seen between 1974 and 2015. The authors also studied the hepatic transcriptome, serum proteome, liver macrophage polarization, and oxidative and inflammatory profiles of Hmbs -/- mice chronically treated by hemin, and extended the investigations to 5 explanted livers from recurrent AIP patients. <a href="#57" class="mim-tip-reference" title="Schmitt, C., Lenglet, H., Yu, A., Delaby, C., Benecke, A., Lefebvre, T., Letteron, P., Paradis, V., Wahlin, S., Sandberg, S., Harper, P., Sardh, E., and 16 others. <strong>Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.</strong> J. Intern. Med. 284: 78-91, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29498764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29498764</a>] [<a href="https://doi.org/10.1111/joim.12750" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29498764">Schmitt et al. (2018)</a> found that the introduction of hemin into the pharmacopeia coincided with a 4.4-fold increase in the prevalence of chronic patients. Moreover, both in animal model and in human liver, frequent hemin infusions generated a chronic inflammatory hepatic disease which induced HMOX1 (<a href="/entry/141250">141250</a>) remotely to hemin treatment and maintained a high ALAS1 level responsible for recurrence. <a href="#57" class="mim-tip-reference" title="Schmitt, C., Lenglet, H., Yu, A., Delaby, C., Benecke, A., Lefebvre, T., Letteron, P., Paradis, V., Wahlin, S., Sandberg, S., Harper, P., Sardh, E., and 16 others. <strong>Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.</strong> J. Intern. Med. 284: 78-91, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29498764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29498764</a>] [<a href="https://doi.org/10.1111/joim.12750" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29498764">Schmitt et al. (2018)</a> suggested that hemin should be restricted to severe neurovisceral crisis only and that alternative treatments targeting the liver, such as ALAS1 and HMOX1 inhibitors, and antiinflammatory therapies should be considered instead of hemin in patients with recurrent AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29498764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#53" class="mim-tip-reference" title="Sardh, E., Harper, P., Balwani, M., Stein, P., Rees, D., Bissell, D. M., Desnick, R., Parker, C., Phillips, J., Bonkovsky, H. L., Vassiliou, D., Penz, C., and 9 others. <strong>Phase 1 trial of an RNA interference therapy for acute intermittent porphyria.</strong> New Eng. J. Med. 380: 549-558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30726693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30726693</a>] [<a href="https://doi.org/10.1056/NEJMoa1807838" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30726693">Sardh et al. (2019)</a> conducted a phase 1 trial of givosiran, an RNA interference therapeutic agent that reduces hepatic ALAS1 mRNA levels, in patients with acute intermittent porphyria. Part A (single injection of an ascending dose) and part B (multiple injections of an ascending dose) were conducted in 23 patients with no attacks in the preceding 6 months. Part C (multiple injections) was conducted in 17 patients who had recurrent attacks. Safety, pharmacokinetic, pharmacodynamic, and exploratory efficacy outcomes were evaluated. Common adverse events included nasopharyngitis, abdominal pain, and diarrhea. Serious adverse events occurred in 6 patients who received givosiran in parts A through C combined. In part C, all 6 patients who were assigned to receive once-monthly injections of givosiran had sustained reductions in ALAS1 mRNA, delta aminolevulinic acid (ALA), and porphobilinogen (PBG) levels to near normal. These reductions were associated with a 79% lower mean annualized attack rate than that observed with placebo. <a href="#53" class="mim-tip-reference" title="Sardh, E., Harper, P., Balwani, M., Stein, P., Rees, D., Bissell, D. M., Desnick, R., Parker, C., Phillips, J., Bonkovsky, H. L., Vassiliou, D., Penz, C., and 9 others. <strong>Phase 1 trial of an RNA interference therapy for acute intermittent porphyria.</strong> New Eng. J. Med. 380: 549-558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30726693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30726693</a>] [<a href="https://doi.org/10.1056/NEJMoa1807838" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30726693">Sardh et al. (2019)</a> concluded that once-monthly injections of givosiran in patients who had recurrent porphyria attacks resulted in mainly low-grade adverse events, reductions in induced ALAS1 mRNA levels, nearly normalized levels of the neurotoxic intermediates ALA and PBG, and a lower attack rate than that observed with placebo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30726693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>A high prevalence of AIP is known in northern Sweden, where Waldenstrom's classic observations were made (<a href="#69" class="mim-tip-reference" title="Waldenstrom, J. <strong>Studies on the incidence and heredity of acute porphyria in Sweden.</strong> Acta Genet. Statist. Med. 6: 122-131, 1956.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13354248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13354248</a>]" pmid="13354248">Waldenstrom, 1956</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13354248" 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>AIP occurs with very low prevalence, perhaps 1 in 50,000, probably in all ethnic groups (<a href="#66" class="mim-tip-reference" title="Tschudy, D. P., Valsamis, M., Magnussen, C. R. <strong>Acute intermittent porphyria: clinical and selected research aspects.</strong> Ann. Intern. Med. 83: 851-864, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1106284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1106284</a>] [<a href="https://doi.org/10.7326/0003-4819-83-6-851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1106284">Tschudy et al., 1975</a>), including blacks (<a href="#23" class="mim-tip-reference" title="Kreimer-Birnbaum, M., Bannerman, R. M., El Khatib, M., Franco-Saenz, R. <strong>Afro-Americans and acute intermittent porphyria.</strong> Int. J. Biochem. 12: 795-799, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7450135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7450135</a>] [<a href="https://doi.org/10.1016/0020-711x(80)90165-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7450135">Kreimer-Birnbaum et al., 1980</a>), but figures for prevalence based on manifest AIP, i.e., acute attacks, greatly underestimate the number of persons with latent AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7450135+1106284" 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="#30" class="mim-tip-reference" title="Lee, J.-S., Lundin, G., Lannfelt, L., Forsell, L., Picat, C., Grandchamp, B., Anvret, M. <strong>Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria.</strong> Hum. Genet. 87: 484-488, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679034</a>] [<a href="https://doi.org/10.1007/BF00197173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1679034">Lee et al. (1991)</a> stated that the prevalence of AIP in Lappland, northern Sweden, was 1 in 1,500. They identified 3 different disease haplotypes among 28 Swedish AIP families. The haplotype designated 2/1/1/2 was the most frequent, segregating with AIP in 10 of 28 families. <a href="#28" class="mim-tip-reference" title="Lee, J.-S., Anvret, M. <strong>Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria.</strong> Proc. Nat. Acad. Sci. 88: 10912-10915, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1961762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1961762</a>] [<a href="https://doi.org/10.1073/pnas.88.23.10912" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1961762">Lee and Anvret (1991)</a> identified a mutation in the HMBS gene (W198X; <a href="/entry/609806#0012">609806.0012</a>) in 15 of 33 AIP families from Lappland, Sweden. Genealogic data showed that 12 of the 15 were related, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1679034+1961762" 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 28 Finnish families representing 72% of all AIP families in the Finnish population of 5 million, <a href="#20" class="mim-tip-reference" title="Kauppinen, R., Mustajoki, S., Pihlaja, H., Peltonen, L., Mustajoki, P. <strong>Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.</strong> Hum. Molec. Genet. 4: 215-222, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7757070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7757070</a>] [<a href="https://doi.org/10.1093/hmg/4.2.215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7757070">Kauppinen et al. (1995)</a> found 19 different mutations in the HMBS gene: 13 novel mutations, including 1 de novo event, and 6 previously characterized mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7757070" 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="Floderus, Y., Shoolingin-Jordan, P. M., Harper, P. <strong>Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene.</strong> Clin. Genet. 62: 288-297, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12372055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12372055</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620406.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12372055">Floderus et al. (2002)</a> stated that the prevalence of AIP in Sweden is about 1 in 10,000. Among Swedish AIP kindreds, they identified 27 novel HMBS mutations, bringing the total number of known mutations in Sweden to 39. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12372055" 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="Kevelam, S. H., Neeleman, R. A., Waisfisz, Q., Friesema, E. C. H., Langendonk, J. G., van der Knaap, M. S. <strong>Acute intermittent porphyria-related leukoencephalopathy.</strong> Neurology 87: 1258-1265, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27558376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27558376</a>] [<a href="https://doi.org/10.1212/WNL.0000000000003129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27558376">Kevelam et al. (2016)</a> stated that the carrier frequency of heterozygous HMBS mutations in European countries is estimated at 1 in 75,000 individuals, but less than 10% of the carriers actually develop acute porphyric attacks. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27558376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#33" class="mim-tip-reference" title="Loftus, L. S., Arnold, W. N. <strong>Vincent van Gogh's illness: acute intermittent porphyria?</strong> Brit. Med. J. 303: 1589-1591, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1773180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1773180</a>] [<a href="https://doi.org/10.1136/bmj.303.6817.1589" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1773180">Loftus and Arnold (1991)</a> suggested that Vincent van Gogh had suffered from attacks of acute intermittent porphyria, exacerbated by malnutrition and absinthe abuse. They suggested that this would best explain the abruptness of the onset and recovery from attacks. It has been suggested that George III had porphyria variegata (<a href="/entry/176200">176200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1773180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>During study of the pathogenesis of the neurologic symptoms of AIP, <a href="#31" class="mim-tip-reference" title="Lindberg, R. L. P., Porcher, C., Grandchamp, B., Ledermann, B., Burki, K., Brandner, S., Aguzzi, A., Meyer, U. A. <strong>Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.</strong> Nature Genet. 12: 195-199, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8563760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8563760</a>] [<a href="https://doi.org/10.1038/ng0296-195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8563760">Lindberg et al. (1996)</a> generated Pbgd (HMBS; <a href="/entry/609806">609806</a>)-deficient mice by gene targeting. These mice exhibited typical biochemical characteristics of human AIP, including decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity, and massively increased urinary excretion of the heme precursor delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioral tests revealed decreased motor function and histopathologic findings, including axonal neuropathy and neurologic muscle atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8563760" 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="#51" class="mim-tip-reference" title="Puy, H., Deybach, J.-C., Bogdan, A., Callebert, J., Baumgartner, M., Voisin, P., Nordmann, Y., Touitou, Y. <strong>Increased delta-aminolevulinic acid and decreased pineal melatonin production: a common event in acute porphyria studies in the rat.</strong> J. Clin. Invest. 97: 104-110, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8550820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8550820</a>] [<a href="https://doi.org/10.1172/JCI118376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8550820">Puy et al. (1996)</a> noted that a porphyric rat model showed increased plasma concentration and brain uptake of tryptophan and increased synthesis of serotonin in the nervous system. The increased concentration of tryptophan and serotonin may be partly due to the hepatic heme deficiency decreasing the activity of the liver cytosolic enzyme heme-dependent tryptophan pyrrolase. Injection of heme lowered heme precursors, tryptophan, and serotonin to normal levels, but did not increase melatonin, which is produced from tryptophan. <a href="#51" class="mim-tip-reference" title="Puy, H., Deybach, J.-C., Bogdan, A., Callebert, J., Baumgartner, M., Voisin, P., Nordmann, Y., Touitou, Y. <strong>Increased delta-aminolevulinic acid and decreased pineal melatonin production: a common event in acute porphyria studies in the rat.</strong> J. Clin. Invest. 97: 104-110, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8550820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8550820</a>] [<a href="https://doi.org/10.1172/JCI118376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8550820">Puy et al. (1996)</a> noted that women with AIP demonstrate a rise in serotonin and plasma tryptophan during the attacks, whereas both daytime and nighttime melatonin concentrations are dramatically decreased. From the animal experiments, <a href="#51" class="mim-tip-reference" title="Puy, H., Deybach, J.-C., Bogdan, A., Callebert, J., Baumgartner, M., Voisin, P., Nordmann, Y., Touitou, Y. <strong>Increased delta-aminolevulinic acid and decreased pineal melatonin production: a common event in acute porphyria studies in the rat.</strong> J. Clin. Invest. 97: 104-110, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8550820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8550820</a>] [<a href="https://doi.org/10.1172/JCI118376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8550820">Puy et al. (1996)</a> suggested that delta-aminolevulinic acid is responsible for decreased production of melatonin by the pineal gland. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8550820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Clavero, S., Bishop, D. F., Haskins, M. E., Giger, U., Kauppinen, R., Desnick, R. J. <strong>Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations.</strong> Hum. Molec. Genet. 19: 584-596, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19934113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19934113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19934113[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/10.1093/hmg/ddp525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19934113">Clavero et al. (2010)</a> described a naturally occurring feline model of AIP in 4 unrelated cat lines that presented phenotypically as congenital erythropoietic porphyria (CEP; <a href="/entry/263700">263700</a>). Affected cats had erythrodontia, brownish urine, fluorescent bones, and markedly elevated urinary uroporphyrin and coproporphyrin, consistent with CEP. However, their uroporphyrinogen-III synthase (UROS; <a href="/entry/606938">606938</a>) activities (deficient in CEP) were normal. Notably, affected cats had half-normal Hmbs activities and elevated urinary 5-aminolevulinic acid and porphobilinogen. Sequencing the feline Hmbs gene revealed different mutations in each line, including a duplication, an in-frame 3-bp deletion (842delGAG), and 2 missense (A84T and R149W) mutations. The 842delGAG and R149W mutations were identical to mutations reported in human. Prokaryotic expression of the 842delGAG and R149W mutations resulted in mutant enzymes with less than 1% wildtype activity, whereas the A84T mutation expressed a stable enzyme with approximately 35% of wildtype activity. The discolored teeth from the affected cats contained markedly elevated URO I and III, accounting for the CEP-like phenocopy. In 3 lines, the phenotype was an autosomal dominant trait, while affected cats with the A84T mutation were homozygous, a unique recessive form of AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19934113" 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="#49" class="mim-tip-reference" title="Pulgar, V. M., Yasuda, M., Gan, L., Desnick, R. J., Bonkovsky, H. L. <strong>Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.</strong> Molec. Genet. Metab. 128: 376-381, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30639047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30639047</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30639047[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.2019.01.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30639047">Pulgar et al. (2019)</a> studied mesenteric vascular reactivity as a model of systemic arterial hypertension in AIP in the T1/T2 mouse, a mouse model with a 30% decrease in Pbdg activity. In mesenteric arteries of T1/T2 males and females, constriction in response to phenylephrine was increased after phenobarbital induction compared to uninduced mesenteric arteries from T1/T2 mice and mesenteric arteries from wildtype mice. <a href="#49" class="mim-tip-reference" title="Pulgar, V. M., Yasuda, M., Gan, L., Desnick, R. J., Bonkovsky, H. L. <strong>Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.</strong> Molec. Genet. Metab. 128: 376-381, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30639047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30639047</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30639047[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.2019.01.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30639047">Pulgar et al. (2019)</a> also found that blockade of nitric oxide production further increased phenylephrine maximal response in phenobarbital-treated mesenteric arteries from T1/T2 males and females. However, in contrast to T1/T2 males, T1/T2 females showed decreased sensitivity to phenylephrine after phenobarbital treatment and nitric oxide inhibition compared to wildtype and nonphenobarbital-treated T1/T2 females. Hemin treatment relaxed the constricted mesenteric arteries in T1/T2 males and females with and without phenobarbital induction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30639047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Bosch1977" class="mim-tip-reference" title="Bosch, E. P., Pierach, C. A., Bossenmaier, I., Cardinal, R., Thornson, M. <strong>Effect of hematin in porphyric neuropathy.</strong> Neurology 27: 1053-1056, 1977.">Bosch et al. (1977)</a>; <a href="#Lamon1979" class="mim-tip-reference" title="Lamon, J. M., Frykholm, B. C., Tschudy, D. P. <strong>Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.</strong> J. Med. Genet. 16: 134-139, 1979.">Lamon et al. (1979)</a>; <a href="#McColl1982" class="mim-tip-reference" title="McColl, K. E. L., Moore, M. R., Thompson, G. G., Goldberg, A. <strong>Screening for latent acute intermittent porphyria: the value of measuring both leucocyte delta-aminolaevulinic acid synthase and erythrocyte uroporphyrinogen-1-synthase activities.</strong> J. Med. Genet. 19: 271-276, 1982.">McColl et al. (1982)</a>; <a href="#Morris1981" class="mim-tip-reference" title="Morris, D. L., Dudley, M. D., Pearson, R. D. <strong>Coagulopathy associated with hematin treatment for acute intermittent porphyria.</strong> Ann. Intern. Med. 95: 700-701, 1981.">Morris et al. (1981)</a>; <a href="#Picat1990" class="mim-tip-reference" title="Picat, C., Delfau, M. H., de Rooij, F. W. M., Beukeveld, G. J. J., Wolthers, B. G., Wadman, S. K., Nordmann, Y., Grandchamp, B. <strong>Identification of the mutations in the parents of a patient with a putative compound heterozygosity for acute intermittent porphyria.</strong> J. Inherit. Metab. Dis. 13: 684-686, 1990.">Picat et al. (1990)</a>; <a href="#Tishler1985" class="mim-tip-reference" title="Tishler, P. V., Woodward, B., O'Connor, J., Holbrook, D. A., Seidman, L. J., Hallett, M., Knighton, D. J. <strong>High prevalence of intermittent acute porphyria in a psychiatric patient population.</strong> Am. J. Psychiat. 142: 1430-1436, 1985.">Tishler et al. (1985)</a>; <a href="#Waldenstrom1963" class="mim-tip-reference" title="Waldenstrom, J., Haeger-Aronsen, B. <strong>Different patterns of human porphyria.</strong> Brit. Med. J. 2: 272-276, 1963.">Waldenstrom and Haeger-Aronsen (1963)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Anderson1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, K. E., Bradlow, H. L., Sassa, S., Kappas, A.
|
|
<strong>Studies in porphyria. VIII. Relationship of the 5-alpha-reductive metabolism of steroid hormone to clinical expression of the genetic defect in acute intermittent porphyria.</strong>
|
|
Am. J. Med. 66: 644-650, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/433969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">433969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=433969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(79)91176-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Anderson1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, K. E., Spitz, I. M., Sassa, S., Bardin, C. W., Kappas, A.
|
|
<strong>Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone.</strong>
|
|
New Eng. J. Med. 311: 643-645, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6433194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6433194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6433194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198409063111006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Anderson1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, P. M., Reddy, R. M., Anderson, K. E., Desnick, R. J.
|
|
<strong>Characterization of the porphobilinogen deaminase deficiency in acute intermittent porphyria: immunologic evidence for heterogeneity of the genetic defect.</strong>
|
|
J. Clin. Invest. 68: 1-12, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7251856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7251856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7251856" 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/jci110223" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Astrin1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Astrin, K. H., Desnick, R. J.
|
|
<strong>Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene.</strong>
|
|
Hum. Mutat. 4: 243-252, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7866402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7866402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7866402" 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.1380040403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Astrup1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Astrup, E. G.
|
|
<strong>Family studies on the activity of uroporphyrinogen I synthase in diagnosis of acute intermittent porphyria.</strong>
|
|
Clin. Sci. Molec. Med. 54: 251-256, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/630801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">630801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=630801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/cs0540251" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Becker1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Becker, D. M., Kramer, S.
|
|
<strong>The neurological manifestations of porphyria: a review.</strong>
|
|
Medicine 56: 411-423, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/329053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">329053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=329053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00005792-197709000-00003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bissell2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bissell, D. M., Anderson, K. E., Bonkovsky, H. L.
|
|
<strong>Porphyria.</strong>
|
|
New Eng. J. Med. 377: 862-872, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28854095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28854095</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28854095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMra1608634" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bosch1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bosch, E. P., Pierach, C. A., Bossenmaier, I., Cardinal, R., Thornson, M.
|
|
<strong>Effect of hematin in porphyric neuropathy.</strong>
|
|
Neurology 27: 1053-1056, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/200860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">200860</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=200860" 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.27.11.1053" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Clavero2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clavero, S., Bishop, D. F., Haskins, M. E., Giger, U., Kauppinen, R., Desnick, R. J.
|
|
<strong>Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations.</strong>
|
|
Hum. Molec. Genet. 19: 584-596, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19934113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19934113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19934113[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=19934113" 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/ddp525" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Desnick1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Desnick, R. J., Ostasiewicz, L. T., Tishler, P. A., Mustajoki, P.
|
|
<strong>Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. Demonstration of noncatalytic enzyme intermediates stabilized by bound substrate.</strong>
|
|
J. Clin. Invest. 76: 865-874, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3897290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3897290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3897290" 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/JCI112044" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Dhar1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dhar, G., Bossenmaier, I., Cardinal, R., Petryka, Z. J., Watson, C. J.
|
|
<strong>Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission.</strong>
|
|
Acta Med. Scand. 203: 437-443, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/665312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">665312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=665312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.0954-6820.1978.tb14903.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Doss1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Doss, M. O.
|
|
<strong>Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies.</strong>
|
|
Clin. Genet. 35: 146-151, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2721023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2721023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2721023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1989.tb02920.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Floderus2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Floderus, Y., Shoolingin-Jordan, P. M., Harper, P.
|
|
<strong>Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene.</strong>
|
|
Clin. Genet. 62: 288-297, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12372055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12372055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12372055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2002.620406.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Goetsch1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goetsch, C. A., Bissell, D. M.
|
|
<strong>Instability of hematin used in the treatment of acute hepatic porphyria.</strong>
|
|
New Eng. J. Med. 315: 235-238, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3724815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3724815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3724815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198607243150406" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Goldberg1959" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldberg, A.
|
|
<strong>Acute intermittent porphyria.</strong>
|
|
Quart. J. Med. 28: 183-209, 1959.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13658350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13658350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13658350" 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="16" class="mim-anchor"></a>
|
|
<a id="Goldberg1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldberg, A.
|
|
<strong>Molecular genetics of acute intermittent porphyria. (Editorial)</strong>
|
|
Brit. Med. J. 291: 499-500, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928028</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3928028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.291.6494.499-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Grandchamp1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Delfau, M. H., Picat, C., de Rooij, F. W. M., Nordmann, Y.
|
|
<strong>Heterogeneity of the molecular defects in acute intermittent porphyria. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 47 (suppl.): A156 only, 1990.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Grandchamp1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Picat, C., de Rooij, F., Beaumont, C., Wilson, P., Deybach, J. C., Nordmann, Y.
|
|
<strong>A point mutation G-to-A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria.</strong>
|
|
Nucleic Acids Res. 17: 6637-6649, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2789372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2789372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2789372" 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/nar/17.16.6637" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Grandchamp1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Picat, C., Mignotte, V., Wilson, J. H. P., te Velde, K., Sandkuyl, L., Romeo, P. H., Goossens, M., Nordmann, Y.
|
|
<strong>Tissue-specific splicing mutation in acute intermittent porphyria.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 661-664, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2563167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2563167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2563167" 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.86.2.661" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Kauppinen1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kauppinen, R., Mustajoki, S., Pihlaja, H., Peltonen, L., Mustajoki, P.
|
|
<strong>Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.</strong>
|
|
Hum. Molec. Genet. 4: 215-222, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7757070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7757070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7757070" 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/4.2.215" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Kauppinen1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kauppinen, R., Peltonen, L., Palotie, A., Mustajoki, P.
|
|
<strong>RFLP analysis of three different types of acute intermittent porphyria.</strong>
|
|
Hum. Genet. 85: 160-164, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973403</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973403" 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/BF00193189" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Kevelam2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kevelam, S. H., Neeleman, R. A., Waisfisz, Q., Friesema, E. C. H., Langendonk, J. G., van der Knaap, M. S.
|
|
<strong>Acute intermittent porphyria-related leukoencephalopathy.</strong>
|
|
Neurology 87: 1258-1265, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27558376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27558376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27558376" 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.0000000000003129" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Kreimer-Birnbaum1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kreimer-Birnbaum, M., Bannerman, R. M., El Khatib, M., Franco-Saenz, R.
|
|
<strong>Afro-Americans and acute intermittent porphyria.</strong>
|
|
Int. J. Biochem. 12: 795-799, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7450135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7450135</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7450135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0020-711x(80)90165-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Kreimer-Birnbaum1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kreimer-Birnbaum, M.
|
|
<strong>Uroporphyrinogen synthase in human blood: developmental studies.</strong>
|
|
Life Sci. 17: 1473-1478, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1207410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1207410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1207410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0024-3205(75)90169-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Laiwah1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laiwah, A. A. C. Y., Mactier, R., McColl, K. E. L., Moore, M. R., Goldberg, A.
|
|
<strong>Early-onset chronic renal failure as a complication of acute intermittent porphyria.</strong>
|
|
Quart. J. Med. 52: 92-98, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6878621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6878621</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6878621" 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="26" class="mim-anchor"></a>
|
|
<a id="Lamon1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamon, J. M., Frykholm, B. C., Hess, R. A., Tschudy, D. P.
|
|
<strong>Hematin therapy for acute porphyria.</strong>
|
|
Medicine 58: 252-269, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/449661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">449661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=449661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00005792-197905000-00005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lamon1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamon, J. M., Frykholm, B. C., Tschudy, D. P.
|
|
<strong>Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.</strong>
|
|
J. Med. Genet. 16: 134-139, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/458830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">458830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=458830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.16.2.134" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Lee1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Anvret, M.
|
|
<strong>Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 10912-10915, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1961762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1961762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1961762" 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.88.23.10912" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Lee1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Lindsten, J., Anvret, M.
|
|
<strong>Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction.</strong>
|
|
Hum. Genet. 84: 241-243, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2303246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2303246</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2303246" 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/BF00200567" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Lee1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Lundin, G., Lannfelt, L., Forsell, L., Picat, C., Grandchamp, B., Anvret, M.
|
|
<strong>Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria.</strong>
|
|
Hum. Genet. 87: 484-488, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1679034" 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/BF00197173" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Lindberg1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lindberg, R. L. P., Porcher, C., Grandchamp, B., Ledermann, B., Burki, K., Brandner, S., Aguzzi, A., Meyer, U. A.
|
|
<strong>Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.</strong>
|
|
Nature Genet. 12: 195-199, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8563760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8563760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8563760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0296-195" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Llewellyn1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Llewellyn, D. H., Elder, G. H., Kalsheker, N. A., Marsh, O. W. M., Harrison, P. R., Grandchamp, B., Picat, C., Nordmann, Y., Romeo, P. H., Goossens, M.
|
|
<strong>DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria.</strong>
|
|
Lancet 334: 706-708, 1987. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2888941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2888941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2888941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(87)91073-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Loftus1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loftus, L. S., Arnold, W. N.
|
|
<strong>Vincent van Gogh's illness: acute intermittent porphyria?</strong>
|
|
Brit. Med. J. 303: 1589-1591, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1773180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1773180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1773180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.303.6817.1589" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Marsden2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marsden, J. T., Rees, D. C.
|
|
<strong>Urinary excretion of porphyrins, porphobilinogen and delta-aminolaevulinic acid following an attack of acute intermittent porphyria.</strong>
|
|
J. Clin. Path. 67: 60-65, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23908454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23908454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23908454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jclinpath-2012-201367" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="McColl1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Moore, M. R., Thompson, G. G., Goldberg, A.
|
|
<strong>Screening for latent acute intermittent porphyria: the value of measuring both leucocyte delta-aminolaevulinic acid synthase and erythrocyte uroporphyrinogen-1-synthase activities.</strong>
|
|
J. Med. Genet. 19: 271-276, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7120315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7120315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7120315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.19.4.271" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="McColl1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R.
|
|
<strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong>
|
|
Lancet 326: 796-799, 1985. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2864531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(85)90793-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="McColl1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Thompson, G. T., Moore, M. R., Goldberg, A.
|
|
<strong>Haematin therapy and leucocyte gamma-aminolaevulinic-acid-synthase activity in prolonged attack of acute porphyria.</strong>
|
|
Lancet 313: 133-134, 1979. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/84154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">84154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=84154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(79)90522-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Meyer1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Schmid, R.
|
|
<strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Meyer1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Strand, L. J., Doss, M., Rees, A. C., Marver, H. S.
|
|
<strong>Intermittent acute porphyria--demonstration of a genetic defect in porphobilinogen metabolism.</strong>
|
|
New Eng. J. Med. 286: 1277-1282, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5024458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5024458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5024458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM197206152862401" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Morris1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morris, D. L., Dudley, M. D., Pearson, R. D.
|
|
<strong>Coagulopathy associated with hematin treatment for acute intermittent porphyria.</strong>
|
|
Ann. Intern. Med. 95: 700-701, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7305149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7305149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7305149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-95-6-700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Mustajoki1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mustajoki, P., Desnick, R. J.
|
|
<strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong>
|
|
Brit. Med. J. 291: 505-509, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3928029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3928029</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3928029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.291.6494.505" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Mustajoki1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria.</strong>
|
|
Ann. Intern. Med. 95: 162-166, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258864</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7258864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-95-2-162" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Norton1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Norton, B., Lanyon, W. G., Moore, M. R., Porteous, M., Youngs, G. R., Connor, J. M.
|
|
<strong>Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism.</strong>
|
|
Hum. Genet. 91: 576-578, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8340112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8340112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8340112" 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/BF00205083" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Norton1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Norton, B., Lanyon, W. G., Moore, M. R., Youngs, G. R., Tomlinson, J. E. M., Aitken, D. A., Connor, J. M.
|
|
<strong>Evidence for a second genetic locus for porphyrin metabolism on chromosome 11q. (Abstract)</strong>
|
|
J. Med. Genet. 28: 551-552, 1991.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Petrides1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petrides, P. E.
|
|
<strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong>
|
|
Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10343207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10343207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10343207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000029859" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Picat1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Picat, C., Delfau, M. H., de Rooij, F. W. M., Beukeveld, G. J. J., Wolthers, B. G., Wadman, S. K., Nordmann, Y., Grandchamp, B.
|
|
<strong>Identification of the mutations in the parents of a patient with a putative compound heterozygosity for acute intermittent porphyria.</strong>
|
|
J. Inherit. Metab. Dis. 13: 684-686, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2246852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2246852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2246852" 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/BF01799567" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Pischik2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pischik, E., Kauppinen, R.
|
|
<strong>An update of clinical management of acute intermittent porphyria.</strong>
|
|
Appl. Clin. Genet. 8: 201-214, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26366103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26366103</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26366103[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=26366103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2147/TACG.S48605" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Poblete-Gutierrez2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poblete-Gutierrez, P., Wiederholt, T., Martinez-Mir, A., Merk, H. F., Connor, J. M., Christiano, A. M., Frank, J.
|
|
<strong>Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene.</strong>
|
|
Physiol. Res. 55 (Suppl. 2): S137-S144, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17298217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17298217</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17298217" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.33549/physiolres.930000.55.S2.137" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Pulgar2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulgar, V. M., Yasuda, M., Gan, L., Desnick, R. J., Bonkovsky, H. L.
|
|
<strong>Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.</strong>
|
|
Molec. Genet. Metab. 128: 376-381, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30639047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30639047</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30639047[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=30639047" 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.2019.01.005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Puy1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Puy, H., Deybach, J. C., Lamoril, J., Robreau, A. M., Da Silva, V., Gouya, L., Grandchamp, B., Nordmann, Y.
|
|
<strong>Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.</strong>
|
|
Am. J. Hum. Genet. 60: 1373-1383, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/515455" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Puy1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Puy, H., Deybach, J.-C., Bogdan, A., Callebert, J., Baumgartner, M., Voisin, P., Nordmann, Y., Touitou, Y.
|
|
<strong>Increased delta-aminolevulinic acid and decreased pineal melatonin production: a common event in acute porphyria studies in the rat.</strong>
|
|
J. Clin. Invest. 97: 104-110, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8550820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8550820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8550820" 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/JCI118376" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Puy1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Puy, H., Gross, U., Deybach, J. C., Robreau, A. M., Frank, M., Nordmann, Y., Doss, M.
|
|
<strong>Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria.</strong>
|
|
Hum. Genet. 103: 570-575, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9860299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9860299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9860299" 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/s004390050871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Sardh2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sardh, E., Harper, P., Balwani, M., Stein, P., Rees, D., Bissell, D. M., Desnick, R., Parker, C., Phillips, J., Bonkovsky, H. L., Vassiliou, D., Penz, C., and 9 others.
|
|
<strong>Phase 1 trial of an RNA interference therapy for acute intermittent porphyria.</strong>
|
|
New Eng. J. Med. 380: 549-558, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30726693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30726693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30726693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa1807838" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Sassa1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A.
|
|
<strong>A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease.</strong>
|
|
Proc. Nat. Acad. Sci. 71: 732-736, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4522787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4522787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4522787" 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.71.3.732" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Sassa1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sassa, S., Solish, G., Levere, R. D., Kappas, A.
|
|
<strong>Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait.</strong>
|
|
J. Exp. Med. 142: 722-731, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1165472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1165472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1165472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.142.3.722" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Sassa1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sassa, S., Zalar, G. L., Kappas, A.
|
|
<strong>Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.</strong>
|
|
J. Clin. Invest. 61: 499-508, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/621286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">621286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=621286" 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/JCI108961" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Schmitt2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schmitt, C., Lenglet, H., Yu, A., Delaby, C., Benecke, A., Lefebvre, T., Letteron, P., Paradis, V., Wahlin, S., Sandberg, S., Harper, P., Sardh, E., and 16 others.
|
|
<strong>Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.</strong>
|
|
J. Intern. Med. 284: 78-91, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29498764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29498764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29498764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/joim.12750" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Scobie1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scobie, G. A., Urquhart, A. J., Elder, G. H., Kalsheker, N. A., Llewellyn, D. H., Smyth, J., Harrison, P. R.
|
|
<strong>Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene.</strong>
|
|
Hum. Genet. 85: 157-159, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973402" 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/BF00193188" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Solis2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Solis, C., Martinez-Bermejo, A., Naidich, T. P., Kaufmann, W. E., Astrin, K. H., Bishop, D. F., Desnick, R. J.
|
|
<strong>Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias.</strong>
|
|
Arch. Neurol. 61: 1764-1770, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15534187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15534187</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15534187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.61.11.1764" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Soonawalla2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soonawalla, Z. F., Orug, T., Badminton, M. N., Elder, G. H., Rhodes, J. M., Bramhall, S. R., Elias, E.
|
|
<strong>Liver transplantation as a cure for acute intermittent porphyria.</strong>
|
|
Lancet 363: 705-706, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15001330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15001330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15001330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0140-6736(04)15646-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Srugo1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Srugo, I., Said, E., Korman, S., Jaffe, M.
|
|
<strong>Acute intermittent porphyria--an unusual cause of 'surgical' abdomen: response to propranolol therapy.</strong>
|
|
Europ. J. Pediat. 146: 305-308, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3595653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3595653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3595653" 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/BF00716482" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Stein1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stein, J. A., Tschudy, D. P.
|
|
<strong>Acute intermittent porphyria: a clinical and biochemical study of 46 patients.</strong>
|
|
Medicine 49: 1-16, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4907358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4907358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4907358" 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="63" class="mim-anchor"></a>
|
|
<a id="Strand1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strand, L. J., Felsher, B. F., Redeker, A. G., Marver, H. S.
|
|
<strong>Heme biosynthesis in intermittent acute porphyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity.</strong>
|
|
Proc. Nat. Acad. Sci. 67: 1315-1320, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5274461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5274461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5274461" 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.67.3.1315" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Strand1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strand, L. J., Meyer, U. A., Felsher, B. F., Redeker, A. G., Marver, H. S.
|
|
<strong>Decreased red cell uroporphyrinogen I synthetase activity in intermittent acute porphyria.</strong>
|
|
J. Clin. Invest. 51: 2530-2536, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5056653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5056653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5056653" 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/JCI107068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Tishler1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tishler, P. V., Woodward, B., O'Connor, J., Holbrook, D. A., Seidman, L. J., Hallett, M., Knighton, D. J.
|
|
<strong>High prevalence of intermittent acute porphyria in a psychiatric patient population.</strong>
|
|
Am. J. Psychiat. 142: 1430-1436, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4073306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4073306</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4073306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1176/ajp.142.12.1430" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Tschudy1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tschudy, D. P., Valsamis, M., Magnussen, C. R.
|
|
<strong>Acute intermittent porphyria: clinical and selected research aspects.</strong>
|
|
Ann. Intern. Med. 83: 851-864, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1106284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1106284</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1106284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-83-6-851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Verma1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verma, A., Nye, J. S., Snyder, S. H.
|
|
<strong>Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 2256-2260, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031675</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3031675" 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.84.8.2256" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Waldenstrom1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waldenstrom, J., Haeger-Aronsen, B.
|
|
<strong>Different patterns of human porphyria.</strong>
|
|
Brit. Med. J. 2: 272-276, 1963.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13998428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13998428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13998428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.2.5352.272" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Waldenstrom1956" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waldenstrom, J.
|
|
<strong>Studies on the incidence and heredity of acute porphyria in Sweden.</strong>
|
|
Acta Genet. Statist. Med. 6: 122-131, 1956.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13354248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13354248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13354248" 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="70" class="mim-anchor"></a>
|
|
<a id="Watson1964" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watson, C. J., Bossenmaier, I.
|
|
<strong>Present status of the Ehrlich aldehyde reaction for urinary porphobilinogen.</strong>
|
|
JAMA 190: 501-504, 1964.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14198005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14198005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14198005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.1964.03070190021004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Whatley2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whatley, S. D., Roberts, A. G., Llewellyn, D. H., Bennett, C. P., Garrett, C., Elder, G. H.
|
|
<strong>Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene.</strong>
|
|
Hum. Genet. 107: 243-248, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11071386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11071386</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11071386" 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/s004390000356" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Whatley1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whatley, S. D., Woolf, J. R., Elder, G. H.
|
|
<strong>Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations.</strong>
|
|
Hum. Genet. 104: 505-510, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10453740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10453740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10453740" 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/s004390050995" 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 : 05/29/2020
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 03/22/2019<br>Ada Hamosh - updated : 05/23/2018<br>George E. Tiller - updated : 2/8/2011<br>Cassandra L. Kniffin - updated : 5/22/2009<br>Ada Hamosh - updated : 7/31/2007<br>Cassandra L. Kniffin - reorganized : 1/5/2006<br>Cassandra L. Kniffin - updated : 12/28/2005<br>Victor A. McKusick - updated : 4/17/2003<br>Victor A. McKusick - updated : 11/6/2002<br>Victor A. McKusick - updated : 10/3/2000<br>Victor A. McKusick - updated : 10/28/1999<br>Victor A. McKusick - updated : 8/31/1999<br>Victor A. McKusick - updated : 8/17/1999<br>Victor A. McKusick - updated : 7/6/1999<br>Victor A. McKusick - updated : 12/10/1998<br>Ethylin Wang Jabs - updated : 7/9/1997<br>Stylianos E. Antonarakis - updated : 7/18/1997<br>Victor A. McKusick - updated : 6/17/1997<br>Stylianos E. Antonarakis - updated : 7/4/1996
|
|
</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 : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/20/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/19/2024<br>ckniffin : 02/08/2024<br>carol : 09/28/2020<br>carol : 05/29/2020<br>carol : 04/29/2020<br>carol : 10/30/2019<br>alopez : 03/22/2019<br>carol : 06/20/2018<br>carol : 05/29/2018<br>carol : 05/23/2018<br>carol : 10/31/2017<br>carol : 02/28/2017<br>carol : 07/09/2016<br>carol : 3/11/2015<br>terry : 4/21/2011<br>terry : 3/14/2011<br>wwang : 3/11/2011<br>terry : 2/8/2011<br>carol : 8/6/2010<br>terry : 6/3/2009<br>wwang : 6/3/2009<br>ckniffin : 5/22/2009<br>terry : 4/8/2009<br>alopez : 8/3/2007<br>terry : 7/31/2007<br>carol : 1/5/2006<br>ckniffin : 12/28/2005<br>carol : 3/17/2004<br>tkritzer : 2/6/2004<br>tkritzer : 5/1/2003<br>terry : 4/17/2003<br>carol : 11/13/2002<br>tkritzer : 11/11/2002<br>terry : 11/6/2002<br>mcapotos : 10/12/2000<br>mcapotos : 10/12/2000<br>mcapotos : 10/9/2000<br>terry : 10/3/2000<br>carol : 11/4/1999<br>terry : 10/28/1999<br>jlewis : 8/31/1999<br>terry : 8/17/1999<br>carol : 7/19/1999<br>carol : 7/19/1999<br>terry : 7/6/1999<br>mgross : 3/17/1999<br>carol : 12/15/1998<br>terry : 12/10/1998<br>carol : 7/9/1998<br>alopez : 7/8/1998<br>mark : 9/11/1997<br>alopez : 9/9/1997<br>alopez : 9/8/1997<br>alopez : 9/8/1997<br>alopez : 8/4/1997<br>terry : 7/18/1997<br>terry : 7/18/1997<br>alopez : 7/10/1997<br>terry : 6/23/1997<br>terry : 6/17/1997<br>alopez : 6/2/1997<br>terry : 8/16/1996<br>marlene : 8/6/1996<br>terry : 7/26/1996<br>carol : 7/4/1996<br>mark : 2/5/1996<br>terry : 2/1/1996<br>mark : 1/29/1996<br>terry : 1/29/1996<br>mark : 7/12/1995<br>terry : 12/22/1994<br>pfoster : 11/3/1994<br>davew : 8/19/1994<br>mimadm : 4/29/1994<br>warfield : 4/12/1994
|
|
</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> 176000
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PORPHYRIA, ACUTE INTERMITTENT; AIP
|
|
|
|
</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">
|
|
PORPHYRIA, SWEDISH TYPE<br />
|
|
PORPHOBILINOGEN DEAMINASE DEFICIENCY<br />
|
|
PBGD DEFICIENCY<br />
|
|
UROPORPHYRINOGEN SYNTHASE DEFICIENCY<br />
|
|
UPS DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
PORPHYRIA, ACUTE INTERMITTENT, NONERYTHROID VARIANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
PORPHYRIA, CHESTER TYPE, INCLUDED; PORC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 234422006, 276263005, 84816006;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 79276;
|
|
|
|
|
|
<strong>DO:</strong> 3890;
|
|
|
|
|
|
</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">
|
|
11q23.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Porphyria, acute intermittent
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
HMBS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609806
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
11q23.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Porphyria, acute intermittent, nonerythroid variant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
HMBS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609806
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that acute intermittent porphyria (AIP) is caused by heterozygous mutation in the gene encoding hydroxymethylbilane synthase (HMBS; 609806), also referred to as porphobilinogen deaminase (PBGD), on chromosome 11q23.</p><p>Biallelic mutation in the HMBS gene causes porphyria-related leukoencephalopathy (LENCEP; 620711) and porphyria-related encephalopathy (ENCEP; 620704), both of which are autosomal recessive disorders with persistent and progressive neurologic features.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Porphyrias are inherited defects in the biosynthesis of heme. Acute intermittent porphyria (AIP), the most common form of porphyria, is an autosomal dominant disorder characterized by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances. The disorder is notably incompletely penetrant: fewer than 10% of heterozygous mutation carriers actually develop acute porphyric attacks. Acute attacks rarely occur before puberty; they may be precipitated by porphyrinogenic drugs such as barbiturates and sulfonamides (for list, see Tschudy et al., 1975), some of which are known to induce the earlier rate-controlling step in heme synthesis, delta-aminolevulinic acid (ALA) synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women. The precipitants cause increased ALAS1 (125290) activity and increased levels of the porphyrin precursors ALA and PBG. The half-normal hepatic HMBS activity in heterozygous AIP patients is insufficient to prevent pathologic accumulation of these precursors, which are most likely responsible for the symptoms (Petrides, 1998; Solis et al., 2004; Kevelam et al., 2016). </p><p>In the classic form of AIP, both the ubiquitous 'nonerythroid' housekeeping HMBS isoform and the 'erythroid' HMBS isoform are deficient. However, about 5% of families have the 'nonerythroid variant' of AIP, with a defect only in the ubiquitous nonerythroid HMBS isoform and normal levels of the erythroid HMBS isoform. Clinical characteristics in the 2 forms are identical; diagnostic methods based on the level of enzyme in erythrocytes are ineffective (Puy et al., 1998; Petrides, 1998; Whatley et al., 2000). </p><p>There are several other forms of porphyria: see porphyria cutanea tarda (176100), variegata porphyria (176200), coproporphyria (121300), acute hepatic porphyria (125270), and congenital erythropoietic porphyria (263700).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Acute intermittent porphyria is characterized clinically by acute episodes of a variety of gastrointestinal and neuropathic symptoms; between episodes, the patient is healthy. Abdominal pain is the most common symptom, sometimes with constipation and urinary retention; paraesthesias and paralysis also occur, and death may result from respiratory paralysis (Goldberg, 1959; Stein and Tschudy, 1970; Becker and Kramer, 1977). Many other phenomena, including seizures, psychotic episodes, and hypertension, may occur in acute attacks. </p><p>From a survey of AIP cases in the west of Scotland, Laiwah et al. (1983) observed an association with early-onset chronic renal failure. Porphyria-induced hypertension was considered the most likely causal factor, but enhanced susceptibility to analgesic nephropathy and nephrotoxic effects of porphyrins and their precursors were mentioned as possibilities. </p><p>Marsden and Rees (2014) measured urine ALA, PBG, and total urine porphyrin (TUP) excretion in 20 patients with AIP following an attack of acute porphyria for 3 months to 23 years after their last documented acute attack. Urinary concentrations of all metabolites remained elevated for many years. The urinary half-life of TUP was 5.3 years, ALA 7.7 years, and PBG 10.6 years. Even after 20 years, PBG concentrations remained elevated above the normal range. Marsden and Rees (2014) concluded that whereas measurement of urine PBG is useful to diagnose the first attack of AIP, it is not helpful as a diagnostic tool in subsequent attacks. </p><p>McColl et al. (1985) identified a form of acute porphyria in a large family in Chester, U.K. Patients presented with attacks of neurovisceral dysfunction; none had cutaneous photosensitivity. Biochemically, the pattern of excretion of heme precursors varied between individuals. Some had a pattern of acute intermittent porphyria, others showed that of variegate porphyria, and some showed an intermediate pattern. A dual enzyme deficiency was found in peripheral blood cells; reduced activity was found in both PBGD, as in AIP, and protoporphyrinogen oxidase (PPOX; 600923), as in variegate porphyria. McColl et al. (1985) initially thought that this was a new form of porphyria. The finding of Poblete-Gutierrez et al. (2006) of a mutation in the HMBS gene in affected individuals (see MOLECULAR GENETICS) confirmed that Chester type porphyria is a variant of AIP. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The essential biochemical finding in acute attacks of AIP is increased urinary excretion of the HMBS precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG); this is the basis for the Watson-Schwartz test (Watson and Bossenmaier, 1964). Many latent AIP subjects never have acute attacks, but some intermittently excrete excess porphyrin precursors in urine without having symptoms. Porphyrins may be formed in the urine from the precursors (Waldenstrom, 1956). </p><p>Anderson et al. (1979) described abnormalities in steroid metabolism in AIP patients. </p><p>Among 22 unrelated families with AIP, Anderson et al. (1981) found differences in the pattern of the 5 stable enzyme-substrate intermediates (A, B, C, D, E) of PBG-deaminase separated by anion-exchange chromatography of erythrocyte lysates. In most patients, the elution profile was similar to the normal with each intermediate reduced about 50%. Some heterozygotes had a second profile in which the C intermediate had disproportionately higher activity than the A or B intermediates; this pattern was observed during an acute attack, suggesting that induction of the enzyme depends on substrate concentrations. </p><p>Verma et al. (1987) found that porphyrins are endogenous ligands for a 'peripheral type' of benzodiazepine receptor, which is selectively associated with the outer mitochondrial membrane. The anxiolytic effects of benzodiazepines are mediated by a 'central' benzodiazepine receptor, located primarily in the brain. The findings may have relevance to the neuropsychiatric aspects of AIP. </p><p>Mustajoki and Desnick (1985) used biochemical and immunologic techniques to characterize 4 mutant types of porphobilinogen deaminase in 68 AIP patients from 33 unrelated families in Finland. About 80% of the mutant enzymes were cross-reactive immunologic material (CRM)-negative and fell into 2 types: those in which PBGD levels and enzyme activity were half-normal in all tissues, and a large kindred with normal erythrocyte PBGD levels. The remainder of the families had CRM-positive mutations, including an unusual group that had increased levels of immunoreactive, non-catalytic enzyme. Mustajoki and Desnick (1985) suggested that the CRM-positive patients of the second type have milder disease. </p><p>Desnick et al. (1985) further characterized the 4 classes of mutations in AIP by studying 165 AIP heterozygotes from 92 unrelated families. The majority of patients had CRM-negative mutations with half-normal PBGD activity; these were designated 'CRM-negative type 1.' In 3 families, designated 'CRM-negative type 2,' symptomatic patients had increased urinary delta-ALA and PBG with normal levels of erythrocyte PBGD activity. Eleven families had CRM-positive, noncatalytic PBGD. Of these, a subset of patients had increased levels of noncatalytic PBGD with increased levels of substrate-bound intermediates, suggestive of increased binding affinity. The findings indicated allelic heterogeneity for mutations in the PBGD gene. </p><p><strong><em>Nonerythroid Variant of AIP</em></strong></p><p>
|
|
Mustajoki (1981) reported a large kindred in which 10 members had AIP with normal erythrocyte PBG-deaminase activity. This form is referred to as the 'nonerythroid variant' of AIP. Forty-nine other Finnish patients with AIP who were unrelated to this kindred had the usual low activity of PBG-deaminase. Mustajoki (1981) suggested that the large kindred represented a variant form of AIP in which the enzyme defect was not expressed in erythrocytes. </p><p>In a study of affected members from 22 unrelated families with AIP, Anderson et al. (1981) demonstrated heterogeneity of the erythrocyte porphobilinogen deaminase defect. Although affected members from 21 families had absent CRM to the PBGD protein, all 7 AIP heterozygotes from 1 family of Basque origin had positive CRM results detected in red cell lysates. Further studies showed that this family had a noncatalytic, immunoreactive protein. </p><p>Mustajoki and Desnick (1985) and Desnick et al. (1985) also identified patients with AIP who had normal levels and activity of erythrocyte PBG-deaminase. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Acute intermittent porphyria, and several other genetic porphyrias, are unusual among enzyme deficiency states in that symptoms are manifest in the heterozygous state, consistent with autosomal dominant inheritance (Meyer and Schmid, 1978).</p><p>Doss (1989) described 4 unrelated individuals with coexistent AIP, caused by deficiency of PBGD, and porphyria cutanea tarda (176100), caused by deficiency of uroporphyrinogen decarboxylase (UROD; 613521). The patients manifested clinical courses of both diseases. Family studies showed that in 1 case the dually affected father transmitted both deficiencies to 1 son and only 1 deficiency to a second son. The findings were consistent with the nonlinkage and nonallelism of the 2 genes underlying the disorders. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mustajoki and Desnick (1985) provided a useful illustration of the putative mutation sites in the heme-synthesis pathway in each of 6 forms of porphyria. </p><p>In patients with AIP, porphobilinogen deaminase activity reduced to approximately half the normal level was demonstrated first in liver (Strand et al., 1970), and subsequently in cultured fibroblasts and red blood cells (Meyer et al., 1972; Strand et al., 1972; Sassa et al., 1974; Kreimer-Birnbaum, 1975). In family studies, most individuals can be characterized as having either clearly normal or 50% decreased levels of PBGD activity, but intermediate values are sometimes found (Sassa et al., 1974; Astrup, 1978; Kreimer-Birnbaum et al., 1980). </p><p>Goldberg (1985) wrote that allelic heterogeneity in AIP may be a factor 'among others, such as drugs, diet, and endogenous hormones, which determine whether the latent state in one patient may continue without incident or, in another, may be shattered by a painful and crippling attack.' </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In 33 unrelated patients with acute intermittent porphyria, Llewellyn et al. (1987) found linkage to a common 2-allele MspI RFLP of the PBGD gene (maximum lod score of 3.14 with no recombinants). In 30 patients, no cross-reacting immunologic material was produced by the mutant allele. A major gene deletion was excluded as the cause of the CRM-negative mutation in 18 heterozygous families. </p><p>By PCR, Lee et al. (1990) amplified polymorphic sites in the PBGD gene that could be used for linkage analysis in AIP families. </p><p>Scobie et al. (1990) identified three 2-allele RFLPs in the PBGD gene, each with allele frequencies close to 0.50. Marked linkage disequilibrium limited the number of observed haplotypes to 4, of which 1 was uncommon. No common haplotype was observed among 47 unrelated AIP patients. </p><p>In 3 Finnish families, each with a different subtype of AIP (CRM-negative with low red cell enzyme activity; CRM-positive with low enzyme activity; CRM-negative with normal enzyme activity), Kauppinen et al. (1990) found evidence of tight linkage to PBGD RFLPs. Among 62 family members tested, 30 had a familial disease-associated haplotype; in 5 of them, conventional tests for AIP were normal, and in 1, uncertain. The authors concluded that RFLP analysis could be used to detect gene carriers and to help in the diagnosis of persons with uncertain results in other tests. </p><p>In the family from Chester, U.K. reported by McColl et al. (1985) Norton et al. (1991, 1993) identified a multipoint maximum lod score of 7.33 at a distance less than 1 cM proximal to D11S351. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a large Dutch family with the nonerythroid variant of AIP, Grandchamp et al. (1989) identified a heterozygous splice site mutation in intron 1 of the HMBS gene (609806.0001). The mutation interrupted the sequence coding for the nonerythroid isoform of PBGD; thus, expression of the erythroid isoform was unaffected. In a patient with CRM-positive AIP, Grandchamp et al. (1989) identified a mutation in the HMBS gene, resulting in the skipping of exon 12 (609806.0002). </p><p>In affected members of 11 different families with either CRM-negative or CRM-positive AIP, Grandchamp et al. (1990) identified 7 different point mutations in the HMBS gene.</p><p>Astrin and Desnick (1994) reviewed the 26 mutations in the HMBS identified to that time. </p><p>Puy et al. (1997) performed molecular analysis of the PBGD gene by denaturing gradient gel electrophoresis followed by direct sequencing in 405 subjects from 121 unrelated French-Caucasian AIP families. PBGD mutations were identified in 109 families, but only 78 were of different type, and each of these had a prevalence rate of less than 5%. Among these mutations, 33 had not previously been published. Sixty percent of the 78 mutations were located in 3 exons (exons 10, 12, and 14); 44% were missense, 18% were splice defect, 19% were frameshift, and 16% were nonsense. </p><p>Whatley et al. (1999) reported a prospective comparison of direct automated sequencing of cDNA (in 29 patients) or genomic DNA (in 28 patients) to identify HMBS mutations in 57 patients referred consecutively for mutation analysis; 39 different mutations were identified in 54 patients. The sensitivity of the cDNA and genomic DNA methods was 69% and 95%, respectively, indicating that analysis of genomic DNA provides a higher mutation detection rate. The mutations included 6 missense, 8 splice defects, 10 frameshifts, and 1 nonsense; 25 had not previously been reported. The results defined the extent of allelic heterogeneity and the types (41% missense, 59% truncating) and distribution (35% in exons 10, 12, and 14) of HMBS mutations for AIP in the United Kingdom. </p><p>In affected members of the original family reported by McColl et al. (1985), Poblete-Gutierrez et al. (2006) identified a heterozygous truncating mutation in the HMBS gene (609806.0046). No mutations were found in the PPOX gene. These findings confirmed that Chester type porphyria is a variant of AIP. Poblete-Gutierrez et al. (2006) suggested that the original biochemical studies indicating PPOX deficiency may have been erroneous or misinterpreted. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sassa et al. (1975) noted that the enzyme defect in AIP is expressed in cultured fibroblasts and amniotic cells, making prenatal diagnosis possible. The enzyme can be induced and the defect demonstrated in mitogen-stimulated lymphocytes (Sassa et al., 1978). </p><p>Puy et al. (1997) found that the standard PBGD enzymatic screening method for gene-carrier detection had 95% concordancy with the molecular-based diagnosis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Most acute attacks, if correctly recognized, settle with supportive treatment; dextrose infusion and high carbohydrate intake may be helpful (Stein and Tschudy, 1970). Successful treatment by infusion of hematin, which is a specific feedback inhibitor of heme synthesis, has repeatedly been reported (McColl et al., 1979; Lamon et al., 1979), but hematin is neither readily available nor very soluble and its use may carry a risk of renal damage (Dhar et al., 1978). </p><p>Goetsch and Bissell (1986) described a 22-year-old woman who had had more than 15 acute attacks requiring hospitalization. Hematin was the mainstay of the patient's therapy, eliciting a well-defined clinical and biochemical response after more than 200 infusions. On one occasion, however, the patient did not respond to a batch of hematin that, in retrospect, was found to have deteriorated. Goetsch and Bissell (1986) quantified the instability of hematin and showed that the decay product(s) is ineffective in regulating porphyrin production. The decayed material, furthermore, was found to have anticoagulant effects, thus explaining one of the complications of hematin therapy. </p><p>An experience reported by Anderson et al. (1984) suggests that in women with premenstrual exacerbation of AIP, a long-acting agonist of luteinizing hormone-releasing hormone may be an effective preventive measure. Srugo et al. (1987) described acute intermittent porphyria as the cause of 'surgical abdomen' in a 15-year-old boy. Because hypertension, tachycardia, and paralytic ileus were present, suggesting sympathetic overactivity, the beta-adrenergic blocking agent propranolol was administered in high doses with apparent dramatic improvement. </p><p>In 9 members of a German kindred in which the proband had nonerythroid variant of AIP resulting in a life-threatening coma, Petrides (1998) identified a mutation in the HMBS gene (609806.0001). The newly identified family members were informed of the disease and taught how to prevent porphyric attacks. They were also given medical alert information certificates. Petrides (1998) emphasized the importance of identifying gene carriers as part of the clinical management of AIP. </p><p>Soonawalla et al. (2004) reported a 19-year-old woman with severe AIP who underwent successful treatment with liver transplantation. After the transplant, concentrations of heme precursors in the patient's urine returned to normal and 1.5 years later, her quality of life was good. </p><p>Pischik and Kauppinen (2015) suggested the following clinical management of AIP. During an acute attack, they recommended treatment with heme preparation if the attack was severe or moderate; symptomatic treatment of autonomic dysfunctions, polyneuropathy, and encephalopathy; exclusion of precipitating factor; and adequate nutrition and fluid therapy. During remissions, they recommended exclusion of precipitating factors, including education of patients and family doctors; information about online drug lists; and mutation screening and education for family members. In patients with recurrent attacks, they recommended evaluation of lifestyle; evaluation of hormonal therapy in women; prophylactic heme therapy; and liver transplantation in patients with severe recurrent attacks. They noted that all AIP patients should be followed up for long-term complications including hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. </p><p>Bissell et al. (2017) reviewed the treatment of patients with AIP. The initial management includes reviewing medications that are considered to be risky for such patients and the administration of fluids (preferably 10% dextrose in 0.45% saline), antiemetic agents, analgesic agents, and, if indicated, antiseizure medications. Antiepileptic drugs must be especially carefully considered. Their Table 3 listed probably safe/possibly unsafe/unsafe medications; unsafe drugs included phenytoin, barbiturates of all type, valproic acid, carbamazepine, and primidone as well as oral contraceptives, progestins, carisoprodol, and spironolactone. The authors cited 2 online resources that provide detailed information on the use of drugs in this disorder. The only specific treatment for acute attacks is intravenous heme (Panhematin in the United States and Normosang in Europe). The authors noted that frequent courses of heme can result in hepatic iron buildup and injury due to iron overload. They cited alternatives to intravenous heme that were being developed and were in clinical trials. </p><p>To determine whether chronic hemin administration contributes to the recurrence of acute attacks in AIP, Schmitt et al. (2018) performed a follow-up study of 602 French symptomatic AIP patients, of whom 46 had recurrent AIP, who were seen between 1974 and 2015. The authors also studied the hepatic transcriptome, serum proteome, liver macrophage polarization, and oxidative and inflammatory profiles of Hmbs -/- mice chronically treated by hemin, and extended the investigations to 5 explanted livers from recurrent AIP patients. Schmitt et al. (2018) found that the introduction of hemin into the pharmacopeia coincided with a 4.4-fold increase in the prevalence of chronic patients. Moreover, both in animal model and in human liver, frequent hemin infusions generated a chronic inflammatory hepatic disease which induced HMOX1 (141250) remotely to hemin treatment and maintained a high ALAS1 level responsible for recurrence. Schmitt et al. (2018) suggested that hemin should be restricted to severe neurovisceral crisis only and that alternative treatments targeting the liver, such as ALAS1 and HMOX1 inhibitors, and antiinflammatory therapies should be considered instead of hemin in patients with recurrent AIP. </p><p>Sardh et al. (2019) conducted a phase 1 trial of givosiran, an RNA interference therapeutic agent that reduces hepatic ALAS1 mRNA levels, in patients with acute intermittent porphyria. Part A (single injection of an ascending dose) and part B (multiple injections of an ascending dose) were conducted in 23 patients with no attacks in the preceding 6 months. Part C (multiple injections) was conducted in 17 patients who had recurrent attacks. Safety, pharmacokinetic, pharmacodynamic, and exploratory efficacy outcomes were evaluated. Common adverse events included nasopharyngitis, abdominal pain, and diarrhea. Serious adverse events occurred in 6 patients who received givosiran in parts A through C combined. In part C, all 6 patients who were assigned to receive once-monthly injections of givosiran had sustained reductions in ALAS1 mRNA, delta aminolevulinic acid (ALA), and porphobilinogen (PBG) levels to near normal. These reductions were associated with a 79% lower mean annualized attack rate than that observed with placebo. Sardh et al. (2019) concluded that once-monthly injections of givosiran in patients who had recurrent porphyria attacks resulted in mainly low-grade adverse events, reductions in induced ALAS1 mRNA levels, nearly normalized levels of the neurotoxic intermediates ALA and PBG, and a lower attack rate than that observed with placebo. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A high prevalence of AIP is known in northern Sweden, where Waldenstrom's classic observations were made (Waldenstrom, 1956). </p><p>AIP occurs with very low prevalence, perhaps 1 in 50,000, probably in all ethnic groups (Tschudy et al., 1975), including blacks (Kreimer-Birnbaum et al., 1980), but figures for prevalence based on manifest AIP, i.e., acute attacks, greatly underestimate the number of persons with latent AIP. </p><p>Lee et al. (1991) stated that the prevalence of AIP in Lappland, northern Sweden, was 1 in 1,500. They identified 3 different disease haplotypes among 28 Swedish AIP families. The haplotype designated 2/1/1/2 was the most frequent, segregating with AIP in 10 of 28 families. Lee and Anvret (1991) identified a mutation in the HMBS gene (W198X; 609806.0012) in 15 of 33 AIP families from Lappland, Sweden. Genealogic data showed that 12 of the 15 were related, suggesting a founder effect. </p><p>In 28 Finnish families representing 72% of all AIP families in the Finnish population of 5 million, Kauppinen et al. (1995) found 19 different mutations in the HMBS gene: 13 novel mutations, including 1 de novo event, and 6 previously characterized mutations. </p><p>Floderus et al. (2002) stated that the prevalence of AIP in Sweden is about 1 in 10,000. Among Swedish AIP kindreds, they identified 27 novel HMBS mutations, bringing the total number of known mutations in Sweden to 39. </p><p>Kevelam et al. (2016) stated that the carrier frequency of heterozygous HMBS mutations in European countries is estimated at 1 in 75,000 individuals, but less than 10% of the carriers actually develop acute porphyric attacks. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Loftus and Arnold (1991) suggested that Vincent van Gogh had suffered from attacks of acute intermittent porphyria, exacerbated by malnutrition and absinthe abuse. They suggested that this would best explain the abruptness of the onset and recovery from attacks. It has been suggested that George III had porphyria variegata (176200). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>During study of the pathogenesis of the neurologic symptoms of AIP, Lindberg et al. (1996) generated Pbgd (HMBS; 609806)-deficient mice by gene targeting. These mice exhibited typical biochemical characteristics of human AIP, including decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity, and massively increased urinary excretion of the heme precursor delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioral tests revealed decreased motor function and histopathologic findings, including axonal neuropathy and neurologic muscle atrophy. </p><p>Puy et al. (1996) noted that a porphyric rat model showed increased plasma concentration and brain uptake of tryptophan and increased synthesis of serotonin in the nervous system. The increased concentration of tryptophan and serotonin may be partly due to the hepatic heme deficiency decreasing the activity of the liver cytosolic enzyme heme-dependent tryptophan pyrrolase. Injection of heme lowered heme precursors, tryptophan, and serotonin to normal levels, but did not increase melatonin, which is produced from tryptophan. Puy et al. (1996) noted that women with AIP demonstrate a rise in serotonin and plasma tryptophan during the attacks, whereas both daytime and nighttime melatonin concentrations are dramatically decreased. From the animal experiments, Puy et al. (1996) suggested that delta-aminolevulinic acid is responsible for decreased production of melatonin by the pineal gland. </p><p>Clavero et al. (2010) described a naturally occurring feline model of AIP in 4 unrelated cat lines that presented phenotypically as congenital erythropoietic porphyria (CEP; 263700). Affected cats had erythrodontia, brownish urine, fluorescent bones, and markedly elevated urinary uroporphyrin and coproporphyrin, consistent with CEP. However, their uroporphyrinogen-III synthase (UROS; 606938) activities (deficient in CEP) were normal. Notably, affected cats had half-normal Hmbs activities and elevated urinary 5-aminolevulinic acid and porphobilinogen. Sequencing the feline Hmbs gene revealed different mutations in each line, including a duplication, an in-frame 3-bp deletion (842delGAG), and 2 missense (A84T and R149W) mutations. The 842delGAG and R149W mutations were identical to mutations reported in human. Prokaryotic expression of the 842delGAG and R149W mutations resulted in mutant enzymes with less than 1% wildtype activity, whereas the A84T mutation expressed a stable enzyme with approximately 35% of wildtype activity. The discolored teeth from the affected cats contained markedly elevated URO I and III, accounting for the CEP-like phenocopy. In 3 lines, the phenotype was an autosomal dominant trait, while affected cats with the A84T mutation were homozygous, a unique recessive form of AIP. </p><p>Pulgar et al. (2019) studied mesenteric vascular reactivity as a model of systemic arterial hypertension in AIP in the T1/T2 mouse, a mouse model with a 30% decrease in Pbdg activity. In mesenteric arteries of T1/T2 males and females, constriction in response to phenylephrine was increased after phenobarbital induction compared to uninduced mesenteric arteries from T1/T2 mice and mesenteric arteries from wildtype mice. Pulgar et al. (2019) also found that blockade of nitric oxide production further increased phenylephrine maximal response in phenobarbital-treated mesenteric arteries from T1/T2 males and females. However, in contrast to T1/T2 males, T1/T2 females showed decreased sensitivity to phenylephrine after phenobarbital treatment and nitric oxide inhibition compared to wildtype and nonphenobarbital-treated T1/T2 females. Hemin treatment relaxed the constricted mesenteric arteries in T1/T2 males and females with and without phenobarbital induction. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Bosch et al. (1977); Lamon et al. (1979); McColl et al. (1982);
|
|
Morris et al. (1981); Picat et al. (1990); Tishler et al. (1985);
|
|
Waldenstrom and Haeger-Aronsen (1963)
|
|
</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">
|
|
Anderson, K. E., Bradlow, H. L., Sassa, S., Kappas, A.
|
|
<strong>Studies in porphyria. VIII. Relationship of the 5-alpha-reductive metabolism of steroid hormone to clinical expression of the genetic defect in acute intermittent porphyria.</strong>
|
|
Am. J. Med. 66: 644-650, 1979.
|
|
|
|
|
|
[PubMed: 433969]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(79)91176-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anderson, K. E., Spitz, I. M., Sassa, S., Bardin, C. W., Kappas, A.
|
|
<strong>Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone.</strong>
|
|
New Eng. J. Med. 311: 643-645, 1984.
|
|
|
|
|
|
[PubMed: 6433194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198409063111006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anderson, P. M., Reddy, R. M., Anderson, K. E., Desnick, R. J.
|
|
<strong>Characterization of the porphobilinogen deaminase deficiency in acute intermittent porphyria: immunologic evidence for heterogeneity of the genetic defect.</strong>
|
|
J. Clin. Invest. 68: 1-12, 1981.
|
|
|
|
|
|
[PubMed: 7251856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/jci110223]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Astrin, K. H., Desnick, R. J.
|
|
<strong>Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene.</strong>
|
|
Hum. Mutat. 4: 243-252, 1994.
|
|
|
|
|
|
[PubMed: 7866402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380040403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Astrup, E. G.
|
|
<strong>Family studies on the activity of uroporphyrinogen I synthase in diagnosis of acute intermittent porphyria.</strong>
|
|
Clin. Sci. Molec. Med. 54: 251-256, 1978.
|
|
|
|
|
|
[PubMed: 630801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/cs0540251]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Becker, D. M., Kramer, S.
|
|
<strong>The neurological manifestations of porphyria: a review.</strong>
|
|
Medicine 56: 411-423, 1977.
|
|
|
|
|
|
[PubMed: 329053]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00005792-197709000-00003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bissell, D. M., Anderson, K. E., Bonkovsky, H. L.
|
|
<strong>Porphyria.</strong>
|
|
New Eng. J. Med. 377: 862-872, 2017.
|
|
|
|
|
|
[PubMed: 28854095]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMra1608634]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bosch, E. P., Pierach, C. A., Bossenmaier, I., Cardinal, R., Thornson, M.
|
|
<strong>Effect of hematin in porphyric neuropathy.</strong>
|
|
Neurology 27: 1053-1056, 1977.
|
|
|
|
|
|
[PubMed: 200860]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.27.11.1053]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clavero, S., Bishop, D. F., Haskins, M. E., Giger, U., Kauppinen, R., Desnick, R. J.
|
|
<strong>Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations.</strong>
|
|
Hum. Molec. Genet. 19: 584-596, 2010.
|
|
|
|
|
|
[PubMed: 19934113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp525]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Desnick, R. J., Ostasiewicz, L. T., Tishler, P. A., Mustajoki, P.
|
|
<strong>Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. Demonstration of noncatalytic enzyme intermediates stabilized by bound substrate.</strong>
|
|
J. Clin. Invest. 76: 865-874, 1985.
|
|
|
|
|
|
[PubMed: 3897290]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112044]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dhar, G., Bossenmaier, I., Cardinal, R., Petryka, Z. J., Watson, C. J.
|
|
<strong>Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission.</strong>
|
|
Acta Med. Scand. 203: 437-443, 1978.
|
|
|
|
|
|
[PubMed: 665312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.0954-6820.1978.tb14903.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Doss, M. O.
|
|
<strong>Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies.</strong>
|
|
Clin. Genet. 35: 146-151, 1989.
|
|
|
|
|
|
[PubMed: 2721023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb02920.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Floderus, Y., Shoolingin-Jordan, P. M., Harper, P.
|
|
<strong>Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene.</strong>
|
|
Clin. Genet. 62: 288-297, 2002.
|
|
|
|
|
|
[PubMed: 12372055]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620406.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goetsch, C. A., Bissell, D. M.
|
|
<strong>Instability of hematin used in the treatment of acute hepatic porphyria.</strong>
|
|
New Eng. J. Med. 315: 235-238, 1986.
|
|
|
|
|
|
[PubMed: 3724815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198607243150406]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldberg, A.
|
|
<strong>Acute intermittent porphyria.</strong>
|
|
Quart. J. Med. 28: 183-209, 1959.
|
|
|
|
|
|
[PubMed: 13658350]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldberg, A.
|
|
<strong>Molecular genetics of acute intermittent porphyria. (Editorial)</strong>
|
|
Brit. Med. J. 291: 499-500, 1985.
|
|
|
|
|
|
[PubMed: 3928028]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.291.6494.499-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Delfau, M. H., Picat, C., de Rooij, F. W. M., Nordmann, Y.
|
|
<strong>Heterogeneity of the molecular defects in acute intermittent porphyria. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 47 (suppl.): A156 only, 1990.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Picat, C., de Rooij, F., Beaumont, C., Wilson, P., Deybach, J. C., Nordmann, Y.
|
|
<strong>A point mutation G-to-A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria.</strong>
|
|
Nucleic Acids Res. 17: 6637-6649, 1989.
|
|
|
|
|
|
[PubMed: 2789372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/17.16.6637]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grandchamp, B., Picat, C., Mignotte, V., Wilson, J. H. P., te Velde, K., Sandkuyl, L., Romeo, P. H., Goossens, M., Nordmann, Y.
|
|
<strong>Tissue-specific splicing mutation in acute intermittent porphyria.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 661-664, 1989.
|
|
|
|
|
|
[PubMed: 2563167]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.86.2.661]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kauppinen, R., Mustajoki, S., Pihlaja, H., Peltonen, L., Mustajoki, P.
|
|
<strong>Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.</strong>
|
|
Hum. Molec. Genet. 4: 215-222, 1995.
|
|
|
|
|
|
[PubMed: 7757070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.2.215]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kauppinen, R., Peltonen, L., Palotie, A., Mustajoki, P.
|
|
<strong>RFLP analysis of three different types of acute intermittent porphyria.</strong>
|
|
Hum. Genet. 85: 160-164, 1990.
|
|
|
|
|
|
[PubMed: 1973403]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00193189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kevelam, S. H., Neeleman, R. A., Waisfisz, Q., Friesema, E. C. H., Langendonk, J. G., van der Knaap, M. S.
|
|
<strong>Acute intermittent porphyria-related leukoencephalopathy.</strong>
|
|
Neurology 87: 1258-1265, 2016.
|
|
|
|
|
|
[PubMed: 27558376]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000003129]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kreimer-Birnbaum, M., Bannerman, R. M., El Khatib, M., Franco-Saenz, R.
|
|
<strong>Afro-Americans and acute intermittent porphyria.</strong>
|
|
Int. J. Biochem. 12: 795-799, 1980.
|
|
|
|
|
|
[PubMed: 7450135]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0020-711x(80)90165-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kreimer-Birnbaum, M.
|
|
<strong>Uroporphyrinogen synthase in human blood: developmental studies.</strong>
|
|
Life Sci. 17: 1473-1478, 1975.
|
|
|
|
|
|
[PubMed: 1207410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0024-3205(75)90169-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laiwah, A. A. C. Y., Mactier, R., McColl, K. E. L., Moore, M. R., Goldberg, A.
|
|
<strong>Early-onset chronic renal failure as a complication of acute intermittent porphyria.</strong>
|
|
Quart. J. Med. 52: 92-98, 1983.
|
|
|
|
|
|
[PubMed: 6878621]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lamon, J. M., Frykholm, B. C., Hess, R. A., Tschudy, D. P.
|
|
<strong>Hematin therapy for acute porphyria.</strong>
|
|
Medicine 58: 252-269, 1979.
|
|
|
|
|
|
[PubMed: 449661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00005792-197905000-00005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lamon, J. M., Frykholm, B. C., Tschudy, D. P.
|
|
<strong>Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.</strong>
|
|
J. Med. Genet. 16: 134-139, 1979.
|
|
|
|
|
|
[PubMed: 458830]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.16.2.134]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Anvret, M.
|
|
<strong>Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 10912-10915, 1991.
|
|
|
|
|
|
[PubMed: 1961762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.23.10912]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Lindsten, J., Anvret, M.
|
|
<strong>Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction.</strong>
|
|
Hum. Genet. 84: 241-243, 1990.
|
|
|
|
|
|
[PubMed: 2303246]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00200567]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, J.-S., Lundin, G., Lannfelt, L., Forsell, L., Picat, C., Grandchamp, B., Anvret, M.
|
|
<strong>Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria.</strong>
|
|
Hum. Genet. 87: 484-488, 1991.
|
|
|
|
|
|
[PubMed: 1679034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00197173]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lindberg, R. L. P., Porcher, C., Grandchamp, B., Ledermann, B., Burki, K., Brandner, S., Aguzzi, A., Meyer, U. A.
|
|
<strong>Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.</strong>
|
|
Nature Genet. 12: 195-199, 1996.
|
|
|
|
|
|
[PubMed: 8563760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0296-195]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Llewellyn, D. H., Elder, G. H., Kalsheker, N. A., Marsh, O. W. M., Harrison, P. R., Grandchamp, B., Picat, C., Nordmann, Y., Romeo, P. H., Goossens, M.
|
|
<strong>DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria.</strong>
|
|
Lancet 334: 706-708, 1987. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 2888941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(87)91073-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Loftus, L. S., Arnold, W. N.
|
|
<strong>Vincent van Gogh's illness: acute intermittent porphyria?</strong>
|
|
Brit. Med. J. 303: 1589-1591, 1991.
|
|
|
|
|
|
[PubMed: 1773180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.303.6817.1589]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marsden, J. T., Rees, D. C.
|
|
<strong>Urinary excretion of porphyrins, porphobilinogen and delta-aminolaevulinic acid following an attack of acute intermittent porphyria.</strong>
|
|
J. Clin. Path. 67: 60-65, 2014.
|
|
|
|
|
|
[PubMed: 23908454]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jclinpath-2012-201367]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Moore, M. R., Thompson, G. G., Goldberg, A.
|
|
<strong>Screening for latent acute intermittent porphyria: the value of measuring both leucocyte delta-aminolaevulinic acid synthase and erythrocyte uroporphyrinogen-1-synthase activities.</strong>
|
|
J. Med. Genet. 19: 271-276, 1982.
|
|
|
|
|
|
[PubMed: 7120315]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.19.4.271]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Thompson, G. G., Moore, M. R., Goldberg, A., Church, S. E., Qadiri, M. R., Youngs, G. R.
|
|
<strong>Chester porphyria: biochemical studies of a new form of acute porphyria.</strong>
|
|
Lancet 326: 796-799, 1985. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 2864531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(85)90793-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McColl, K. E. L., Thompson, G. T., Moore, M. R., Goldberg, A.
|
|
<strong>Haematin therapy and leucocyte gamma-aminolaevulinic-acid-synthase activity in prolonged attack of acute porphyria.</strong>
|
|
Lancet 313: 133-134, 1979. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 84154]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(79)90522-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Schmid, R.
|
|
<strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Strand, L. J., Doss, M., Rees, A. C., Marver, H. S.
|
|
<strong>Intermittent acute porphyria--demonstration of a genetic defect in porphobilinogen metabolism.</strong>
|
|
New Eng. J. Med. 286: 1277-1282, 1972.
|
|
|
|
|
|
[PubMed: 5024458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197206152862401]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morris, D. L., Dudley, M. D., Pearson, R. D.
|
|
<strong>Coagulopathy associated with hematin treatment for acute intermittent porphyria.</strong>
|
|
Ann. Intern. Med. 95: 700-701, 1981.
|
|
|
|
|
|
[PubMed: 7305149]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-95-6-700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mustajoki, P., Desnick, R. J.
|
|
<strong>Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.</strong>
|
|
Brit. Med. J. 291: 505-509, 1985.
|
|
|
|
|
|
[PubMed: 3928029]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.291.6494.505]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria.</strong>
|
|
Ann. Intern. Med. 95: 162-166, 1981.
|
|
|
|
|
|
[PubMed: 7258864]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-95-2-162]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Norton, B., Lanyon, W. G., Moore, M. R., Porteous, M., Youngs, G. R., Connor, J. M.
|
|
<strong>Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism.</strong>
|
|
Hum. Genet. 91: 576-578, 1993.
|
|
|
|
|
|
[PubMed: 8340112]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00205083]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Norton, B., Lanyon, W. G., Moore, M. R., Youngs, G. R., Tomlinson, J. E. M., Aitken, D. A., Connor, J. M.
|
|
<strong>Evidence for a second genetic locus for porphyrin metabolism on chromosome 11q. (Abstract)</strong>
|
|
J. Med. Genet. 28: 551-552, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petrides, P. E.
|
|
<strong>Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.</strong>
|
|
Skin Pharmacol. Appl. Skin Physiol. 11: 374-380, 1998.
|
|
|
|
|
|
[PubMed: 10343207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000029859]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Picat, C., Delfau, M. H., de Rooij, F. W. M., Beukeveld, G. J. J., Wolthers, B. G., Wadman, S. K., Nordmann, Y., Grandchamp, B.
|
|
<strong>Identification of the mutations in the parents of a patient with a putative compound heterozygosity for acute intermittent porphyria.</strong>
|
|
J. Inherit. Metab. Dis. 13: 684-686, 1990.
|
|
|
|
|
|
[PubMed: 2246852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01799567]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pischik, E., Kauppinen, R.
|
|
<strong>An update of clinical management of acute intermittent porphyria.</strong>
|
|
Appl. Clin. Genet. 8: 201-214, 2015.
|
|
|
|
|
|
[PubMed: 26366103]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2147/TACG.S48605]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poblete-Gutierrez, P., Wiederholt, T., Martinez-Mir, A., Merk, H. F., Connor, J. M., Christiano, A. M., Frank, J.
|
|
<strong>Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene.</strong>
|
|
Physiol. Res. 55 (Suppl. 2): S137-S144, 2006.
|
|
|
|
|
|
[PubMed: 17298217]
|
|
|
|
|
|
[Full Text: https://doi.org/10.33549/physiolres.930000.55.S2.137]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulgar, V. M., Yasuda, M., Gan, L., Desnick, R. J., Bonkovsky, H. L.
|
|
<strong>Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.</strong>
|
|
Molec. Genet. Metab. 128: 376-381, 2019.
|
|
|
|
|
|
[PubMed: 30639047]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2019.01.005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Puy, H., Deybach, J. C., Lamoril, J., Robreau, A. M., Da Silva, V., Gouya, L., Grandchamp, B., Nordmann, Y.
|
|
<strong>Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.</strong>
|
|
Am. J. Hum. Genet. 60: 1373-1383, 1997.
|
|
|
|
|
|
[PubMed: 9199558]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/515455]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Puy, H., Deybach, J.-C., Bogdan, A., Callebert, J., Baumgartner, M., Voisin, P., Nordmann, Y., Touitou, Y.
|
|
<strong>Increased delta-aminolevulinic acid and decreased pineal melatonin production: a common event in acute porphyria studies in the rat.</strong>
|
|
J. Clin. Invest. 97: 104-110, 1996.
|
|
|
|
|
|
[PubMed: 8550820]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118376]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Puy, H., Gross, U., Deybach, J. C., Robreau, A. M., Frank, M., Nordmann, Y., Doss, M.
|
|
<strong>Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria.</strong>
|
|
Hum. Genet. 103: 570-575, 1998.
|
|
|
|
|
|
[PubMed: 9860299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sardh, E., Harper, P., Balwani, M., Stein, P., Rees, D., Bissell, D. M., Desnick, R., Parker, C., Phillips, J., Bonkovsky, H. L., Vassiliou, D., Penz, C., and 9 others.
|
|
<strong>Phase 1 trial of an RNA interference therapy for acute intermittent porphyria.</strong>
|
|
New Eng. J. Med. 380: 549-558, 2019.
|
|
|
|
|
|
[PubMed: 30726693]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1807838]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A.
|
|
<strong>A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease.</strong>
|
|
Proc. Nat. Acad. Sci. 71: 732-736, 1974.
|
|
|
|
|
|
[PubMed: 4522787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.71.3.732]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sassa, S., Solish, G., Levere, R. D., Kappas, A.
|
|
<strong>Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait.</strong>
|
|
J. Exp. Med. 142: 722-731, 1975.
|
|
|
|
|
|
[PubMed: 1165472]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.142.3.722]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sassa, S., Zalar, G. L., Kappas, A.
|
|
<strong>Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.</strong>
|
|
J. Clin. Invest. 61: 499-508, 1978.
|
|
|
|
|
|
[PubMed: 621286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108961]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schmitt, C., Lenglet, H., Yu, A., Delaby, C., Benecke, A., Lefebvre, T., Letteron, P., Paradis, V., Wahlin, S., Sandberg, S., Harper, P., Sardh, E., and 16 others.
|
|
<strong>Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.</strong>
|
|
J. Intern. Med. 284: 78-91, 2018.
|
|
|
|
|
|
[PubMed: 29498764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/joim.12750]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scobie, G. A., Urquhart, A. J., Elder, G. H., Kalsheker, N. A., Llewellyn, D. H., Smyth, J., Harrison, P. R.
|
|
<strong>Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene.</strong>
|
|
Hum. Genet. 85: 157-159, 1990.
|
|
|
|
|
|
[PubMed: 1973402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00193188]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Solis, C., Martinez-Bermejo, A., Naidich, T. P., Kaufmann, W. E., Astrin, K. H., Bishop, D. F., Desnick, R. J.
|
|
<strong>Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias.</strong>
|
|
Arch. Neurol. 61: 1764-1770, 2004.
|
|
|
|
|
|
[PubMed: 15534187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.61.11.1764]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soonawalla, Z. F., Orug, T., Badminton, M. N., Elder, G. H., Rhodes, J. M., Bramhall, S. R., Elias, E.
|
|
<strong>Liver transplantation as a cure for acute intermittent porphyria.</strong>
|
|
Lancet 363: 705-706, 2004.
|
|
|
|
|
|
[PubMed: 15001330]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(04)15646-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Srugo, I., Said, E., Korman, S., Jaffe, M.
|
|
<strong>Acute intermittent porphyria--an unusual cause of 'surgical' abdomen: response to propranolol therapy.</strong>
|
|
Europ. J. Pediat. 146: 305-308, 1987.
|
|
|
|
|
|
[PubMed: 3595653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00716482]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stein, J. A., Tschudy, D. P.
|
|
<strong>Acute intermittent porphyria: a clinical and biochemical study of 46 patients.</strong>
|
|
Medicine 49: 1-16, 1970.
|
|
|
|
|
|
[PubMed: 4907358]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strand, L. J., Felsher, B. F., Redeker, A. G., Marver, H. S.
|
|
<strong>Heme biosynthesis in intermittent acute porphyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity.</strong>
|
|
Proc. Nat. Acad. Sci. 67: 1315-1320, 1970.
|
|
|
|
|
|
[PubMed: 5274461]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.67.3.1315]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strand, L. J., Meyer, U. A., Felsher, B. F., Redeker, A. G., Marver, H. S.
|
|
<strong>Decreased red cell uroporphyrinogen I synthetase activity in intermittent acute porphyria.</strong>
|
|
J. Clin. Invest. 51: 2530-2536, 1972.
|
|
|
|
|
|
[PubMed: 5056653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI107068]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tishler, P. V., Woodward, B., O'Connor, J., Holbrook, D. A., Seidman, L. J., Hallett, M., Knighton, D. J.
|
|
<strong>High prevalence of intermittent acute porphyria in a psychiatric patient population.</strong>
|
|
Am. J. Psychiat. 142: 1430-1436, 1985.
|
|
|
|
|
|
[PubMed: 4073306]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1176/ajp.142.12.1430]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tschudy, D. P., Valsamis, M., Magnussen, C. R.
|
|
<strong>Acute intermittent porphyria: clinical and selected research aspects.</strong>
|
|
Ann. Intern. Med. 83: 851-864, 1975.
|
|
|
|
|
|
[PubMed: 1106284]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-83-6-851]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verma, A., Nye, J. S., Snyder, S. H.
|
|
<strong>Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 2256-2260, 1987.
|
|
|
|
|
|
[PubMed: 3031675]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.84.8.2256]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waldenstrom, J., Haeger-Aronsen, B.
|
|
<strong>Different patterns of human porphyria.</strong>
|
|
Brit. Med. J. 2: 272-276, 1963.
|
|
|
|
|
|
[PubMed: 13998428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.2.5352.272]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waldenstrom, J.
|
|
<strong>Studies on the incidence and heredity of acute porphyria in Sweden.</strong>
|
|
Acta Genet. Statist. Med. 6: 122-131, 1956.
|
|
|
|
|
|
[PubMed: 13354248]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watson, C. J., Bossenmaier, I.
|
|
<strong>Present status of the Ehrlich aldehyde reaction for urinary porphobilinogen.</strong>
|
|
JAMA 190: 501-504, 1964.
|
|
|
|
|
|
[PubMed: 14198005]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.1964.03070190021004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whatley, S. D., Roberts, A. G., Llewellyn, D. H., Bennett, C. P., Garrett, C., Elder, G. H.
|
|
<strong>Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene.</strong>
|
|
Hum. Genet. 107: 243-248, 2000.
|
|
|
|
|
|
[PubMed: 11071386]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390000356]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whatley, S. D., Woolf, J. R., Elder, G. H.
|
|
<strong>Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations.</strong>
|
|
Hum. Genet. 104: 505-510, 1999.
|
|
|
|
|
|
[PubMed: 10453740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050995]
|
|
|
|
|
|
</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 : 05/29/2020<br>Ada Hamosh - updated : 03/22/2019<br>Ada Hamosh - updated : 05/23/2018<br>George E. Tiller - updated : 2/8/2011<br>Cassandra L. Kniffin - updated : 5/22/2009<br>Ada Hamosh - updated : 7/31/2007<br>Cassandra L. Kniffin - reorganized : 1/5/2006<br>Cassandra L. Kniffin - updated : 12/28/2005<br>Victor A. McKusick - updated : 4/17/2003<br>Victor A. McKusick - updated : 11/6/2002<br>Victor A. McKusick - updated : 10/3/2000<br>Victor A. McKusick - updated : 10/28/1999<br>Victor A. McKusick - updated : 8/31/1999<br>Victor A. McKusick - updated : 8/17/1999<br>Victor A. McKusick - updated : 7/6/1999<br>Victor A. McKusick - updated : 12/10/1998<br>Ethylin Wang Jabs - updated : 7/9/1997<br>Stylianos E. Antonarakis - updated : 7/18/1997<br>Victor A. McKusick - updated : 6/17/1997<br>Stylianos E. Antonarakis - updated : 7/4/1996
|
|
</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 : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/20/2024<br>alopez : 02/19/2024<br>ckniffin : 02/08/2024<br>carol : 09/28/2020<br>carol : 05/29/2020<br>carol : 04/29/2020<br>carol : 10/30/2019<br>alopez : 03/22/2019<br>carol : 06/20/2018<br>carol : 05/29/2018<br>carol : 05/23/2018<br>carol : 10/31/2017<br>carol : 02/28/2017<br>carol : 07/09/2016<br>carol : 3/11/2015<br>terry : 4/21/2011<br>terry : 3/14/2011<br>wwang : 3/11/2011<br>terry : 2/8/2011<br>carol : 8/6/2010<br>terry : 6/3/2009<br>wwang : 6/3/2009<br>ckniffin : 5/22/2009<br>terry : 4/8/2009<br>alopez : 8/3/2007<br>terry : 7/31/2007<br>carol : 1/5/2006<br>ckniffin : 12/28/2005<br>carol : 3/17/2004<br>tkritzer : 2/6/2004<br>tkritzer : 5/1/2003<br>terry : 4/17/2003<br>carol : 11/13/2002<br>tkritzer : 11/11/2002<br>terry : 11/6/2002<br>mcapotos : 10/12/2000<br>mcapotos : 10/12/2000<br>mcapotos : 10/9/2000<br>terry : 10/3/2000<br>carol : 11/4/1999<br>terry : 10/28/1999<br>jlewis : 8/31/1999<br>terry : 8/17/1999<br>carol : 7/19/1999<br>carol : 7/19/1999<br>terry : 7/6/1999<br>mgross : 3/17/1999<br>carol : 12/15/1998<br>terry : 12/10/1998<br>carol : 7/9/1998<br>alopez : 7/8/1998<br>mark : 9/11/1997<br>alopez : 9/9/1997<br>alopez : 9/8/1997<br>alopez : 9/8/1997<br>alopez : 8/4/1997<br>terry : 7/18/1997<br>terry : 7/18/1997<br>alopez : 7/10/1997<br>terry : 6/23/1997<br>terry : 6/17/1997<br>alopez : 6/2/1997<br>terry : 8/16/1996<br>marlene : 8/6/1996<br>terry : 7/26/1996<br>carol : 7/4/1996<br>mark : 2/5/1996<br>terry : 2/1/1996<br>mark : 1/29/1996<br>terry : 1/29/1996<br>mark : 7/12/1995<br>terry : 12/22/1994<br>pfoster : 11/3/1994<br>davew : 8/19/1994<br>mimadm : 4/29/1994<br>warfield : 4/12/1994
|
|
</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>
|
|
|
|
|