1294 lines
No EOL
213 KiB
XML
1294 lines
No EOL
213 KiB
XML
<?xml version="1.0" encoding="utf-8"?>
|
|
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">
|
|
|
|
<head><meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
|
|
<!-- AppResources meta begin -->
|
|
<meta name="paf-app-resources" content="" />
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- AppResources meta end -->
|
|
|
|
<!-- TemplateResources meta begin -->
|
|
<meta name="paf_template" content="" />
|
|
|
|
<!-- TemplateResources meta end -->
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK584020" /><meta name="ncbi_domain" content="gene" /><meta name="ncbi_report" content="classic" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK584020/?report=classic" /><meta name="ncbi_pagename" content="Pediatric Genetic Cholestatic Liver Disease Overview - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
|
<!-- Logger end -->
|
|
|
|
<title>Pediatric Genetic Cholestatic Liver Disease Overview - GeneReviews® - NCBI Bookshelf</title>
|
|
|
|
<!-- AppResources external_resources begin -->
|
|
<link rel="stylesheet" href="/core/jig/1.15.2/css/jig.min.css" /><script type="text/javascript" src="/core/jig/1.15.2/js/jig.min.js"></script>
|
|
|
|
<!-- AppResources external_resources end -->
|
|
|
|
<!-- Page meta begin -->
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Pediatric Genetic Cholestatic Liver Disease Overview" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/05/25" /><meta name="citation_author" content="Maria Amendola" /><meta name="citation_author" content="James E Squires" /><meta name="citation_pmid" content="36108118" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK584020/" /><meta name="citation_keywords" content="3 beta-hydroxysteroid dehydrogenase type 7" /><meta name="citation_keywords" content="Aldo-keto reductase family 1 member D1" /><meta name="citation_keywords" content="Alpha-methylacyl-CoA racemase" /><meta name="citation_keywords" content="Bile acid receptor" /><meta name="citation_keywords" content="Bile acid-CoA:amino acid N-acyltransferase" /><meta name="citation_keywords" content="Bile salt export pump" /><meta name="citation_keywords" content="Cytochrome P450 7B1" /><meta name="citation_keywords" content="Inactive ubiquitin carboxyl-terminal hydrolase 53" /><meta name="citation_keywords" content="Kinesin-like protein KIF12" /><meta name="citation_keywords" content="Lipolysis-stimulated lipoprotein receptor" /><meta name="citation_keywords" content="Phosphatidylcholine translocator ABCB4" /><meta name="citation_keywords" content="Phospholipid-transporting ATPase IC" /><meta name="citation_keywords" content="Tight junction protein 2" /><meta name="citation_keywords" content="Unconventional myosin-Vb" /><meta name="citation_keywords" content="ABCB11" /><meta name="citation_keywords" content="ABCB4" /><meta name="citation_keywords" content="AKR1D1" /><meta name="citation_keywords" content="AMACR" /><meta name="citation_keywords" content="ATP8B1" /><meta name="citation_keywords" content="BAAT" /><meta name="citation_keywords" content="CYP7B1" /><meta name="citation_keywords" content="HSD3B7" /><meta name="citation_keywords" content="KIF12" /><meta name="citation_keywords" content="LSR" /><meta name="citation_keywords" content="MYO5B" /><meta name="citation_keywords" content="NR1H4" /><meta name="citation_keywords" content="TJP2" /><meta name="citation_keywords" content="USP53" /><meta name="citation_keywords" content="Pediatric Genetic Cholestatic Liver Disease" /><meta name="citation_keywords" content="Overview" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Pediatric Genetic Cholestatic Liver Disease Overview" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Maria Amendola" /><meta name="DC.Contributor" content="James E Squires" /><meta name="DC.Date" content="2023/05/25" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK584020/" /><meta name="description" content="The purpose of this overview is to:" /><meta name="og:title" content="Pediatric Genetic Cholestatic Liver Disease Overview" /><meta name="og:type" content="book" /><meta name="og:description" content="The purpose of this overview is to:" /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK584020/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/chol-liver-ov/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK584020/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
|
|
|
|
<!-- Page meta end -->
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico" /><meta name="ncbi_phid" content="CE8B80677D4FF69100000000005A004F.m_13" />
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3985586/3808861/4121862/3974050/3917732/251717/4216701/14534/45193/4113719/3849091/3984811/3751656/4033350/3840896/3577051/3852958/4008682/4207974/4206132/4062871/12930/3964959/3854974/36029/4128070/9685/3549676/3609192/3609193/3609213/3395586.css" /><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3411343/3882866.css" media="print" /></head>
|
|
<body class="book-part">
|
|
<div class="grid">
|
|
<div class="col twelve_col nomargin shadow">
|
|
<!-- System messages like service outage or JS required; this is handled by the TemplateResources portlet -->
|
|
<div class="sysmessages">
|
|
<noscript>
|
|
<p class="nojs">
|
|
<strong>Warning:</strong>
|
|
The NCBI web site requires JavaScript to function.
|
|
<a href="/guide/browsers/#enablejs" title="Learn how to enable JavaScript" target="_blank">more...</a>
|
|
</p>
|
|
</noscript>
|
|
</div>
|
|
<!--/.sysmessage-->
|
|
<div class="wrap">
|
|
<div class="page">
|
|
<div class="top">
|
|
<div id="universal_header">
|
|
<section class="usa-banner">
|
|
<div class="usa-accordion">
|
|
<header class="usa-banner-header">
|
|
<div class="usa-grid usa-banner-inner">
|
|
<img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" />
|
|
<p>An official website of the United States government</p>
|
|
<button class="non-usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" type="button">
|
|
<span class="usa-banner-button-text">Here's how you know</span>
|
|
</button>
|
|
</div>
|
|
</header>
|
|
<div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" aria-hidden="true">
|
|
<div class="usa-banner-guidance-gov usa-width-one-half">
|
|
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" />
|
|
<div class="usa-media_block-body">
|
|
<p>
|
|
<strong>The .gov means it's official.</strong>
|
|
<br />
|
|
Federal government websites often end in .gov or .mil. Before
|
|
sharing sensitive information, make sure you're on a federal
|
|
government site.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="usa-banner-guidance-ssl usa-width-one-half">
|
|
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" />
|
|
<div class="usa-media_block-body">
|
|
<p>
|
|
<strong>The site is secure.</strong>
|
|
<br />
|
|
The <strong>https://</strong> ensures that you are connecting to the
|
|
official website and that any information you provide is encrypted
|
|
and transmitted securely.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</section>
|
|
<div class="usa-overlay"></div>
|
|
<header class="ncbi-header" role="banner" data-section="Header">
|
|
|
|
<div class="usa-grid">
|
|
<div class="usa-width-one-whole">
|
|
|
|
<div class="ncbi-header__logo">
|
|
<a href="/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo">
|
|
<img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" />
|
|
</a>
|
|
</div>
|
|
|
|
<div class="ncbi-header__account">
|
|
<a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a>
|
|
<button id="account_info" class="header-button" style="display:none" aria-controls="account_popup" type="button">
|
|
<span class="fa fa-user" aria-hidden="true">
|
|
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" width="20px" height="20px">
|
|
<g style="fill: #fff">
|
|
<ellipse cx="12" cy="8" rx="5" ry="6"></ellipse>
|
|
<path d="M21.8,19.1c-0.9-1.8-2.6-3.3-4.8-4.2c-0.6-0.2-1.3-0.2-1.8,0.1c-1,0.6-2,0.9-3.2,0.9s-2.2-0.3-3.2-0.9 C8.3,14.8,7.6,14.7,7,15c-2.2,0.9-3.9,2.4-4.8,4.2C1.5,20.5,2.6,22,4.1,22h15.8C21.4,22,22.5,20.5,21.8,19.1z"></path>
|
|
</g>
|
|
</svg>
|
|
</span>
|
|
<span class="username desktop-only" aria-hidden="true" id="uname_short"></span>
|
|
<span class="sr-only">Show account info</span>
|
|
</button>
|
|
</div>
|
|
|
|
<div class="ncbi-popup-anchor">
|
|
<div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true">
|
|
<div class="ncbi-popup-head">
|
|
<button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu" type="button">
|
|
<span class="fa fa-times">
|
|
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 48 48" width="24px" height="24px">
|
|
<path d="M38 12.83l-2.83-2.83-11.17 11.17-11.17-11.17-2.83 2.83 11.17 11.17-11.17 11.17 2.83 2.83 11.17-11.17 11.17 11.17 2.83-2.83-11.17-11.17z"></path>
|
|
</svg>
|
|
</span>
|
|
<span class="usa-sr-only">Close</span></button>
|
|
<h4>Account</h4>
|
|
</div>
|
|
<div class="account-user-info">
|
|
Logged in as:<br />
|
|
<b><span class="username" id="uname_long">username</span></b>
|
|
</div>
|
|
<div class="account-links">
|
|
<ul class="usa-unstyled-list">
|
|
<li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li>
|
|
<li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li>
|
|
<li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li>
|
|
<li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li>
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
</div>
|
|
</header>
|
|
<div role="navigation" aria-label="access keys">
|
|
<a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a>
|
|
<a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a>
|
|
<a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a>
|
|
<a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a>
|
|
<a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a>
|
|
</div>
|
|
<section data-section="Alerts">
|
|
<div class="ncbi-alerts-placeholder"></div>
|
|
</section>
|
|
</div>
|
|
<div class="header">
|
|
<div class="res_logo"><h1 class="res_name"><a href="/books/" title="Bookshelf home">Bookshelf</a></h1><h2 class="res_tagline"></h2></div>
|
|
<div class="search"><form method="get" action="/books/"><div class="search_form"><label for="database" class="offscreen_noflow">Search database</label><select id="database"><optgroup label="Recent"><option value="books" selected="selected" data-ac_dict="bookshelf-search">Books</option><option value="pubmed">PubMed</option><option value="clinvar">ClinVar</option><option value="medgen" class="last">MedGen</option></optgroup><optgroup label="All"><option value="gquery">All Databases</option><option value="assembly">Assembly</option><option value="biocollections">Biocollections</option><option value="bioproject">BioProject</option><option value="biosample">BioSample</option><option value="books" data-ac_dict="bookshelf-search">Books</option><option value="clinvar">ClinVar</option><option value="cdd">Conserved Domains</option><option value="gap">dbGaP</option><option value="dbvar">dbVar</option><option value="gene">Gene</option><option value="genome">Genome</option><option value="gds">GEO DataSets</option><option value="geoprofiles">GEO Profiles</option><option value="gtr">GTR</option><option value="ipg">Identical Protein Groups</option><option value="medgen">MedGen</option><option value="mesh">MeSH</option><option value="nlmcatalog">NLM Catalog</option><option value="nuccore">Nucleotide</option><option value="omim">OMIM</option><option value="pmc">PMC</option><option value="protein">Protein</option><option value="proteinclusters">Protein Clusters</option><option value="protfam">Protein Family Models</option><option value="pcassay">PubChem BioAssay</option><option value="pccompound">PubChem Compound</option><option value="pcsubstance">PubChem Substance</option><option value="pubmed">PubMed</option><option value="snp">SNP</option><option value="sra">SRA</option><option value="structure">Structure</option><option value="taxonomy">Taxonomy</option><option value="toolkit">ToolKit</option><option value="toolkitall">ToolKitAll</option><option value="toolkitbookgh">ToolKitBookgh</option></optgroup></select><div class="nowrap"><label for="term" class="offscreen_noflow" accesskey="/">Search term</label><div class="nowrap"><input type="text" name="term" id="term" title="Search Books. Use up and down arrows to choose an item from the autocomplete." value="" class="jig-ncbiclearbutton jig-ncbiautocomplete" data-jigconfig="dictionary:'bookshelf-search',disableUrl:'NcbiSearchBarAutoComplCtrl'" autocomplete="off" data-sbconfig="ds:'no',pjs:'no',afs:'no'" /></div><button id="search" type="submit" class="button_search nowrap" cmd="go">Search</button></div></div></form><ul class="searchlinks inline_list"><li>
|
|
<a href="/books/browse/">Browse Titles</a>
|
|
</li><li>
|
|
<a href="/books/advanced/">Advanced</a>
|
|
</li><li class="help">
|
|
<a href="/books/NBK3833/">Help</a>
|
|
</li><li class="disclaimer">
|
|
<a target="_blank" data-ga-category="literature_resources" data-ga-action="link_click" data-ga-label="disclaimer_link" href="https://www.ncbi.nlm.nih.gov/books/about/disclaimer/">Disclaimer</a>
|
|
</li></ul></div>
|
|
</div>
|
|
|
|
|
|
|
|
<!--<component id="Page" label="headcontent"/>-->
|
|
|
|
</div>
|
|
<div class="content">
|
|
<!-- site messages -->
|
|
<!-- Custom content 1 -->
|
|
<div class="col1">
|
|
|
|
</div>
|
|
|
|
<div class="container">
|
|
<div id="maincontent" class="content eight_col col">
|
|
<!-- Custom content in the left column above book nav -->
|
|
<div class="col2">
|
|
|
|
</div>
|
|
|
|
<!-- Book content -->
|
|
|
|
|
|
<!-- Custom content between navigation and content -->
|
|
<div class="col3">
|
|
|
|
</div>
|
|
|
|
<div class="document">
|
|
<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK584020_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK584020_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/parkinson-overview/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/pmld1/" title="Next page in this title">Next ></a></div></div></div></div></div>
|
|
<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK584020_"><span class="title" itemprop="name">Pediatric Genetic Cholestatic Liver Disease Overview</span></h1><p class="contrib-group"><span itemprop="author">Maria Amendola</span>, MD and <span itemprop="author">James E Squires</span>, MD, MS.</p><a data-jig="ncbitoggler" href="#__NBK584020_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK584020_ai__"><div class="contrib half_rhythm"><span itemprop="author">Maria Amendola</span>, MD<div class="affiliation small">Department of Pediatrics<br />UPMC Children's Hospital of Pittsburgh<br />Pittsburgh, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.phc@iynal.airam" class="oemail">ude.phc@iynal.airam</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">James E Squires</span>, MD, MS<div class="affiliation small">Department of Pediatric Gastroenterology and Hepatology<br />UPMC Children's Hospital of Pittsburgh<br />Pittsburgh, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.phc@2seriuqs.semaj" class="oemail">ude.phc@2seriuqs.semaj</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 15, 2022</span>; Last Revision: <span itemprop="dateModified">May 25, 2023</span>.</p><p><em>Estimated reading time: 26 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="chol-liver-ov.Summary" itemprop="description"><h2 id="_chol-liver-ov_Summary_">Summary</h2><p>The purpose of this overview is to:</p><dl class="temp-labeled-list"><dt>1.</dt><dd><p class="no_top_margin">Briefly describe the common <a href="#chol-liver-ov.Clinical_Characteristics_o">clinical characteristics</a> of inherited cholestatic liver diseases in which cholestasis is a primary manifestation of the underlying causative pathology;</p></dd><dt>2.</dt><dd><p class="no_top_margin">Review the <a href="#chol-liver-ov.Causes_of_Genetic_Cholesta">genetic causes</a> of primary cholestatic liver disease;</p></dd><dt>3.</dt><dd><p class="no_top_margin">Provide an <a href="#chol-liver-ov.Evaluation_Strategies_to_I">evaluation strategy</a> to identify the genetic cause of primary cholestatic liver disease in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> (when possible);</p></dd><dt>4.</dt><dd><p class="no_top_margin">Review high-level dietary, medical, and surgical <a href="#chol-liver-ov.Management">management</a> of primary genetic cholestatic liver disease;</p></dd><dt>5.</dt><dd><p class="no_top_margin">Inform <a href="#chol-liver-ov.Genetic_Counseling">genetic counseling</a> of family members of an individual with primary genetic cholestatic liver disease.</p></dd></dl>
|
|
<p>Note: Disorders in which cholestasis is a secondary manifestation of the underlying causative pathology are outside the scope of this chapter.</p></div><div id="chol-liver-ov.Clinical_Characteristics_o"><h2 id="_chol-liver-ov_Clinical_Characteristics_o_">1. Clinical Characteristics of Genetic Cholestatic Liver Disease</h2><p>For the purposes of this chapter, the term "primary cholestatic liver disease" is used to designate those inherited disorders in which cholestasis is a primary manifestation of the underlying causative pathology (such as transport of bile acids and phospholipids, bile acid synthesis, and bile acid metabolism or transport). Disorders in which cholestasis is a secondary manifestation of the underlying causative pathology are outside the scope of this chapter.</p><p><b>Cholestasis</b> is absent or reduced bile flow associated with a pathologic condition. Cholestasis is suspected in the presence of the following clinical manifestations and is defined by the following laboratory findings.</p><p>
|
|
<b>Clinical manifestations of cholestasis</b>
|
|
</p><ul><li class="half_rhythm"><div>Jaundice (yellowing of the skin and/or mucous membranes and/or peripheral sclera of the eye – i.e., scleral icterus)</div></li><li class="half_rhythm"><div>Pruritus or itching (commonly related to the relative elevation of serum bile acids)</div></li><li class="half_rhythm"><div>Malabsorption of fat-soluble vitamins (i.e., vitamins A, D, E, and K), resulting in:</div><ul><li class="half_rhythm"><div>Poor weight gain</div></li><li class="half_rhythm"><div>Easy bleeding or bruising (secondary to coagulopathy from vitamin K deficiency)</div></li></ul></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li><li class="half_rhythm"><div>Discolored and/or pale stools (i.e., acholic stools)</div></li></ul><p>The first episode of cholestasis may occur in infancy in any of the pediatric genetic disorders discussed in this overview, regardless of the natural history of the disorder.</p><p>The natural history of many genetic cholestatic disorders is progression to fibrosis (i.e., general scarring of the liver secondary to injury) that can be graded 1-4. Cirrhosis, the most severe form of fibrosis, is generally accompanied by other complications such as portal hypertension, synthetic liver dysfunction, and increased risk for hepatocellular carcinoma.</p><p><b>Laboratory findings of</b>
|
|
<b>cholestasis</b></p><ul><li class="half_rhythm"><div class="half_rhythm">Conjugated or direct hyperbilirubinemia</div><div class="half_rhythm">Note: (1) While consensus guidelines recommend evaluation of cholestatic disease for conjugated or direct bilirubin concentrations above 1.0 mg/dL (17 µmol/L) [<a class="bk_pop" href="#chol-liver-ov.REF.fawaz.2017.154">Fawaz et al 2017</a>], others have proposed a more conservative approach, suggesting investigations in individuals with conjugated or direct bilirubin measurements of 0.3 mg/dL (5 µmol/L) [<a class="bk_pop" href="#chol-liver-ov.REF.harpavat.2016.605">Harpavat et al 2016</a>, <a class="bk_pop" href="#chol-liver-ov.REF.feldman.2019.346">Feldman & Sokol 2019</a>]. (2) Conjugated or direct bilirubin levels may not be an accurate marker of cholestasis.</div></li><li class="half_rhythm"><div class="half_rhythm">Gamma-glutamyl transpeptidase (GGTP; also referred to as gamma-glutamyl transferase [GGT]) levels are integral to identifying different causes of cholestatic liver disease, including:</div><ul><li class="half_rhythm"><div>Low-normal GGTP levels in most disorders known as progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a>);</div></li><li class="half_rhythm"><div>Elevated GGTP levels in disorders with abnormal biliary duct morphology or cholangiociliopathies/ciliary development (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a>).</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm">Elevated serum bile acids</div><ul><li class="half_rhythm"><div>While the majority of cholestatic conditions have elevated primary serum bile acids (cholic and chenodeoxycholic acids), the family of bile acid synthetic defect disorders may be defined by the absence of primary bile acids and the presence of atypical bile acids specific to each primary defect (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">Table 2</a>).</div></li><li class="half_rhythm"><div>Elevated alkaline phosphatase is used infrequently to assess children with cholestasis, as it often reflects alternative processes such as bone injury or growth.</div></li></ul></li></ul><p><b>Liver and abdominal ultrasound imaging findings</b> in individuals with pediatric genetic cholestatic liver disease may be nonspecific.</p><p>Liver ultrasound findings may include [<a class="bk_pop" href="#chol-liver-ov.REF.squires.2018.921">Squires & McKiernan 2018</a>]:</p><ul><li class="half_rhythm"><div>Coarseness, nodularity, or increased echogenicity</div></li><li class="half_rhythm"><div>Hepatomegaly</div></li><li class="half_rhythm"><div>Antegrade portal blood flow on Doppler assessment</div></li><li class="half_rhythm"><div>Bile duct abnormalities including:</div><ul><li class="half_rhythm"><div>Dilatation with mechanical obstruction</div></li><li class="half_rhythm"><div>Diminutive extrahepatic ducts and gall bladder abnormalities</div></li></ul></li></ul><p>Abdominal ultrasound may include:</p><ul><li class="half_rhythm"><div>Splenomegaly</div></li><li class="half_rhythm"><div>Ascites</div></li></ul><p><b>Extrahepatic clinical manifestations</b> may be observed in certain metabolic or developmental disorders (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a>).</p></div><div id="chol-liver-ov.Causes_of_Genetic_Cholesta"><h2 id="_chol-liver-ov_Causes_of_Genetic_Cholesta_">2. Causes of Genetic Cholestatic Liver Disease</h2><p>Note: Pathologic cholestasis occurs in one in 2,500 newborns in North America, 40% of which is attributed to biliary atresia, an inflammatory cholangiopathy that requires immediate diagnosis (suggested by liver ultrasound examination and liver biopsy and confirmed with intraoperative cholangiogram) and life-saving surgical intervention [<a class="bk_pop" href="#chol-liver-ov.REF.karpen.2020.115">Karpen 2020</a>].</p><p>The subject of this overview is the estimated 25%-50% of pediatric primary genetic cholestasis NOT related to biliary atresia that has an identifiable genetic etiology [<a class="bk_pop" href="#chol-liver-ov.REF.feldman.2019.346">Feldman & Sokol 2019</a>].</p><p>The genetic disorders discussed in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Tables 1</a>, <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">2</a>, and <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">3</a> of this overview are organized by the mechanism of disease causation and presence of extrahepatic findings:</p><ul><li class="half_rhythm"><div>Disorders of transport of bile acids or phospholipids (<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a>)</div></li><li class="half_rhythm"><div>Disorders of bile acid synthesis (<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">Table 2</a>)</div></li><li class="half_rhythm"><div>Disorders with extrahepatic metabolic or developmental findings (<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a>)</div></li></ul><div id="chol-liver-ov.Disorders_of_Transport_of"><h3>Disorders of Transport of Bile Acids or Phospholipids</h3><p><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a> summarizes primary cholestatic liver disease caused by defects that impair bile acid transport and result in progressive cholestasis. These disorders, many of which have overlapping clinical findings, are historically referred to as progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis (PFIC) and are generally associated with onset in early infancy or childhood. However, it is increasingly apparent that pathogenic variants in PFIC-associated genes can also contribute to the adult-onset diseases benign recurrent intrahepatic cholestasis (BRIC) – intermittent episodes of cholestasis of varying severity – and intrahepatic cholestasis of pregnancy (ICP) – cholestasis, pruritus, and hepatic impairment that manifests with pregnancy and usually resolves completely after delivery. See <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a> for the range of phenotypes observed in association with each PFIC-related <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p><p>Note: (1) Although some investigators have proposed the use of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-based nomenclature (e.g., ATP8B1 deficiency) rather than <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>-based nomenclature (e.g., PFIC1) to enable gene-specific clinical care and facilitate scientific discovery [<a class="bk_pop" href="#chol-liver-ov.REF.biesecker.2021.8">Biesecker et al 2021</a>, <a class="bk_pop" href="#chol-liver-ov.REF.squires.2021.641">Squires & Monga 2021</a>], this chapter primarily relies on historical phenotype-based nomenclature and classification for consistency with their use in most contemporary medical literature. (2) <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a> does not include provisionally identified genes for which data available to date are not sufficient to associate variants with a specific phenotype or an underlying disease mechanism.</p><div id="chol-liver-ov.T.pediatric_genetic_choles" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Genes and Clinical Features of Defects in Transport of Bile Acids or Phospholipids</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder Designation(s)</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" style="text-align:left;vertical-align:middle;">Laboratory<br />Findings</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" style="text-align:left;vertical-align:middle;">PFIC Clinical Features / Comments</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Adult-Onset<br />Phenotypes</th></tr><tr><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">BRIC</th><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ICP</th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ABCB4</i> <sup>2</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC3; MDR3 deficiency (OMIM <a href="https://omim.org/entry/602347" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">602347</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↑↑↑ GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ risk for HCC & CCA; ↑ risk for intrahepatic stone formation; typically AR inheritance but can be AD</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ABCB11</i> <sup>2</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC2; BSEP deficiency (OMIM <a href="https://omim.org/entry/601847" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">601847</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Jaundice, pruritus, & portal HTN; poor growth & malabsorption; rapid progression in 1st 5 yrs; early-onset cirrhosis; ≤15% rate of malignancy (HCC & CCA) in children as young as 13 mos</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATP8B1</i> <sup>2</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">FIC1 deficiency; <a href="/books/n/gene/pfic/">ATP8B1 deficiency</a> (incl PFIC1 & BRIC1)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & bilirubin; ↓ or normal GGTP; ↑ electrolytes on sweat chloride test</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May have profound diarrhea, poor growth, short stature, pancreatic insufficiency, & hearing loss; <sup>3</sup> <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequencies relatively high in Inuit populations of Greenland & northern Canada & Amish kindreds <sup>4, 5</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIF12</i> <sup>6</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">KIF12 deficiency (OMIM <a href="https://omim.org/entry/619662" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619662</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rapid progression to liver fibrosis & portal HTN; progressive sclerosing cholangitis w/age</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>LSR</i> <sup>7</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">LSR deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT, bile acids, & bilirubin; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intractable itching</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MYO5B</i> <sup>2, 8</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC6</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & bilirubin; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Microvillus inclusion disease; liver disease can be transient, progressive, or recurrent.</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NR1H4</i> <sup>2</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC5 (OMIM <a href="https://omim.org/entry/617049" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617049</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & bilirubin; ↓ or normal GGTP; ↑↑ AFP; coagulopathy</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rapid progression to ESLD</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TJP2</i> <sup>9</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC4</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & bilirubin; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe cholestasis & pruritus; rapid progression; ↑ risk for HCC; neurologic or respiratory deficits; high <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequency for <i>TJP2</i>-related genetic cholestatic liver disease among Lancaster County Old Order Amish <sup>10</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>USP53</i> <sup>9</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">USP53 deficiency (OMIM <a href="https://omim.org/entry/619658" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619658</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intractable pruritus & hypocalcemia; w/or w/o progressive hearing loss</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_5 hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Adapted from Tables 1-<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_5/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes5">6</a> in <a class="bk_pop" href="#chol-liver-ov.REF.squires.2018.921">Squires & McKiernan [2018]</a></p></div></dd><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AFP = alpha-fetoprotein; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; AST = aspartate aminotransferase; BSEP = bile salt export pump; BRIC = benign recurrent intrahepatic cholestasis; CCA = cholangiocarcinoma; ESLD = end-stage liver disease; GGTP = gamma-glutamyl transpeptidase; HCC = hepatocellular carcinoma; HTN = hypertension; ICP = intrahepatic cholestasis of pregnancy; PFIC = progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.1.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="chol-liver-ov.TF.1.2"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.goldberg.2020.105">Goldberg & Mack [2020]</a>
|
|
</p></div></dd><dt>3. </dt><dd><div id="chol-liver-ov.TF.1.3"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.henkel.2019.450">Henkel et al [2019]</a>
|
|
</p></div></dd><dt>4. </dt><dd><div id="chol-liver-ov.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.clayton.1969.112">Clayton et al [1969]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.klomp.2000.1337">Klomp et al [2000]</a></p></div></dd><dt>5. </dt><dd><div id="chol-liver-ov.TF.1.5"><p class="no_margin">"Byler disease" refers to severe ATP8B1 deficiency in individuals of Amish ancestry; "Greenland childhood cholestasis" or "Greenland <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> cholestasis" refers to severe ATP8B1 deficiency in individuals of Inuit ancestry.</p></div></dd><dt>6. </dt><dd><div id="chol-liver-ov.TF.1.6"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula et al [2019]</a>
|
|
</p></div></dd><dt>7. </dt><dd><div id="chol-liver-ov.TF.1.7"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula et al [2019]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.uehara.2020.251">Uehara et al [2020]</a></p></div></dd><dt>8. </dt><dd><div id="chol-liver-ov.TF.1.8"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.gonzales.2017.164">Gonzales et al [2017]</a>
|
|
</p></div></dd><dt>9. </dt><dd><div id="chol-liver-ov.TF.1.9"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula et al [2019]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.zhang.2020.1142">Zhang et al [2020]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.alhebbi.2021.151">Alhebbi et al [2021]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.bull.2021.667">Bull et al [2021]</a></p></div></dd><dt>10. </dt><dd><div id="chol-liver-ov.TF.1.10"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.carlton.2003.91">Carlton et al [2003]</a>
|
|
</p></div></dd></dl></div></div></div></div><div id="chol-liver-ov.Disorders_of_Bile_Acid_Syn"><h3>Disorders of Bile Acid Synthesis</h3><p><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">Table 2</a> summarizes primary cholestatic liver disease caused by disorders of bile acid synthesis. These disorders, generally associated with onset in early infancy or childhood, are characterized by fat-soluble vitamin deficiency with growth deficiency.</p><p>There are two main mechanisms by which bile acid synthesis defects can damage the liver:</p><ul><li class="half_rhythm"><div>Defective bile acids affect bile-induced bile flow, resulting in cholestasis.</div></li><li class="half_rhythm"><div>Buildup of intermediates/metabolites from the process of bile acid synthesis are toxic to hepatocytes.</div></li></ul><p>Note: <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">Table 2</a> does not include provisionally identified genes for which data available to date are not sufficient to associate variants with a specific <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> or an underlying disease mechanism.</p><div id="chol-liver-ov.T.pediatric_genetic_choles_1" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Genes and Clinical Features of Disorders of Bile Acid Synthesis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1, 2</sup></th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laboratory Findings</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features / Comments</th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AKR1D1</i> <sup>3</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS2 (OMIM <a href="https://omim.org/entry/235555" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">235555</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↑ GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No pruritus; HSM</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AMACR</i> <sup>3</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS4 (OMIM <a href="https://omim.org/entry/214950" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">214950</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↓ serum bile acids</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Motor neuropathy in adult-onset <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>BAAT</i> <sup>4</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bile acid conjugation defect 1 (OMIM <a href="https://omim.org/entry/619232" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619232</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ or normal AST/ALT</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possible ESLD; high <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequency of <i>BAAT</i>-related genetic cholestatic liver disease in Lancaster County Old Order Amish community <sup>5</sup></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CYP7B1</i> <sup>3</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS3 (OMIM <a href="https://omim.org/entry/613812" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613812</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HSM, synthetic dysfunction</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CYP27A1</i> <sup>6</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ctx/">Cerebrotendinous xanthomatosis</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholestasis w/↓ or normal bile acids</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal onset; neurologic findings & diarrhea</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HSD3B7</i> <sup>3</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS1 (OMIM <a href="https://omim.org/entry/607765" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">607765</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↓ or normal GGTP; ↓ serum bile acids</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most common defect; similar clinically to PFIC1 (see <a href="/books/n/gene/pfic/">ATP8B1 deficiency</a> in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a>) but w/o pruritus or HSM</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Adapted from Tables 1-<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_5/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes5">6</a> in <a class="bk_pop" href="#chol-liver-ov.REF.squires.2018.921">Squires & McKiernan [2018]</a></p></div></dd><dt></dt><dd><div><p class="no_margin">ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBAS = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> defect in bile acid synthesis; ESLD = end-stage liver disease; GGTP = gamma-glutamyl transpeptidase; HSM = hepatosplenomegaly; PFIC = progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.2.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="chol-liver-ov.TF.2.2"><p class="no_margin">Selected references included</p></div></dd><dt>3. </dt><dd><div id="chol-liver-ov.TF.2.3"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.heubi.2007.282">Heubi et al [2007]</a>
|
|
</p></div></dd><dt>4. </dt><dd><div id="chol-liver-ov.TF.2.4"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.setchell.2013.945">Setchell et al [2013]</a>
|
|
</p></div></dd><dt>5. </dt><dd><div id="chol-liver-ov.TF.2.5"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.carlton.2003.91">Carlton et al [2003]</a>
|
|
</p></div></dd><dt>6. </dt><dd><div id="chol-liver-ov.TF.2.6"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.gong.2017.561">Gong et al [2017]</a>
|
|
</p></div></dd></dl></div></div></div></div><div id="chol-liver-ov.Disorders_with_Cholestatic"><h3>Disorders with Cholestatic Liver Disease and Extrahepatic Findings</h3><p><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a> includes genetic disorders with extrahepatic metabolic or developmental findings in which cholestasis is the primary manifestation of underlying disease pathology that can be localized to the liver.</p><p>Note: <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a> does not include provisionally identified genes for which data available to date are not sufficient to associate variants with a specific <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> or an underlying disease mechanism.</p><div id="chol-liver-ov.T.pediatric_genetic_choles_2" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Genes and Clinical Features of Disorders with Extrahepatic Metabolic or Developmental Findings</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s) <sup>1</sup> (Disorder <sup>2</sup>)</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Age of Onset</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laboratory Findings</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features / Comments</th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CFTR</i> <sup>3</sup> (<a href="/books/n/gene/cf/">cystic fibrosis</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood/<br />adolescence</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diagnosis requires ≥2 of following findings:
|
|
<ul><li class="half_rhythm"><div>↑ AST/ALT & GGTP for >6 mos</div></li><li class="half_rhythm"><div>HSM, confirmed on ultrasound</div></li><li class="half_rhythm"><div>Coarseness, nodularity, ↑ echogenicity or portal HTN on ultrasound</div></li><li class="half_rhythm"><div>Liver biopsy w/biliary or multilobular cirrhosis <sup>4</sup></div></li></ul>
|
|
Synthetic dysfunction is usually minimal.</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cystic fibrosis liver disease is diagnosed in 10%-15% of persons w/CF & is cause of mortality in 2%-3% of persons w/CF. <sup>4</sup> Cirrhosis & portal HTN are most clinically significant manifestations. Neonatal cholestasis is possible presenting feature.</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CLDN1</i> <sup>5</sup> (neonatal ichthyosis-sclerosing cholangitis) (OMIM <a href="https://omim.org/entry/607626" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">607626</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ ALT & GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Portal HTN; ichthyosis & alopecia</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>DCDC2</i> <sup>6</sup> (neonatal sclerosing cholangitis) (OMIM <a href="https://omim.org/entry/617394" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617394</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ ALT & GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Acholic stools, HSM, coagulopathy, ascites (variable presentation), renal disease</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HNF1B</i> <sup>7</sup> (HNF1B deficiency) (OMIM <a href="https://omim.org/entry/137920" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">137920</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal to adulthood</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT; ↑ GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spectrum of hepatic involvement ranges from severe neonatal cholestasis to asymptomatic increase of transaminases in adulthood; clinical manifestations incl paucity of intralobular bile ducts sometimes assoc in newborns w/IUGR. HCC has been reported. Other findings can incl kidney involvement (CAKUT, tubulopathy, &/or interstitial kidney disease), MODY5, &/or pancreatic insufficiency.</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>JAG1</i>; <i>NOTCH2</i> <sup>8</sup><br />(<a href="/books/n/gene/alagille/">Alagille syndrome</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑↑↑ GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholestasis, progressing to ESLD in some; butterfly vertebrae, xanthomas, CHD, posterior embryotoxon, vascular abnormalities</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NPC1</i>; <i>NPC2</i> (<a href="/books/n/gene/npc/">Niemann-Pick disease type C</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal to adulthood</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal features incl cholestasis, HSM, & in some cases ALF; neurodegenerative findings in older groups</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PEX</i> genes (<a href="/books/n/gene/pbd/">Zellweger spectrum disorder</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abnormal VLCFA</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholestasis + hepatomegaly; neurologic deficits</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PKHD1</i> <sup>9</sup> (<a href="/books/n/gene/pkd-ar/">polycystic kidney disease, autosomal recessive</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy to adulthood</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abnormal lab findings may be absent in newborns w/ARPKD.</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital hepatic fibrosis; variable dilatation of intrahepatic bile ducts (Caroli syndrome) & dilatation of common bile duct; nephromegaly, HTN, & varying degrees of renal dysfunction</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SCYL1</i> <sup>10</sup> (cholestasis, acute liver failure, & neurodegeneration) (OMIM <a href="https://omim.org/entry/616719" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616719</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholestasis, fibrosis, & recurrent ALF; DD, neuropathy, cerebellar atrophy, ataxia, chronic anemia, skeletal dysplasia</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SERPINA1</i> (<a href="/books/n/gene/alpha1-a/">alpha-1 antitrypsin deficiency</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy to adulthood</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & GGTP in 20%</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal onset in severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> w/cholestasis & progressive liver disease. HCC possible; chronic obstructive lung disease, panniculitis, & vasculitis; rare in Asian populations</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SLC25A13</i> (neonatal intrahepatic cholestasis caused by citrin deficiency) (See <a href="/books/n/gene/citrin/">Citrin Deficiency</a>.)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Age <1 yr</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypoproteinemia, synthetic liver dysfunction; ↑ NH<sub>3</sub>; ↓ glucose</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↓ birth weight, growth restriction; transient cholestasis; resolves by age 1 yr in most</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SLC51A</i> <sup>11</sup> (SLC51A deficiency)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT/ALP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diarrhea & malabsorption, poor weight gain & bleeding; early fibrosis & cirrhosis w/cholestasis</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SLC51B</i> <sup>12</sup> (primary bile acid malabsorption 2) (OMIM <a href="https://omim.org/entry/619481" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619481</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & GGTP; ↑ INR, normal albumin; ↓ fat-soluble vitamins</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital diarrhea; prolonged jaundice in neonatal period</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TALDO1</i> <sup>13</sup> (transadolase 1 deficiency)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT/ALP; normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hepatomegaly, pancytopenia, renal defects, cardiac defects, fetal hydrops, & <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features; ↑ HCC risk</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TTC26</i> <sup>14</sup> (biliary, renal, neurologic & skeletal syndrome) (OMIM <a href="https://omim.org/entry/619534" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619534</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ liver enzymes; ↑ bilirubin; ↑ GGTP in some cases</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac defects, renal abnormalities (small/echogenic kidneys, hydronephrosis), DD, pituitary stalk interruption syndrome</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>VIPAS39</i> (<i>VIPAR</i>); <i>VPS33B</i> (arthrogryposis, renal dysfunction, & cholestasis) (OMIM <a href="https://omim.org/phenotypicSeries/PS208085" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS208085</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ AST/ALT & bilirubin; ↓ or normal GGTP</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arthrogryposis, renal tubular acidosis, & ichthyosis; poor growth; largely fatal in 1st yr of life</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ZFYVE19</i> <sup>15</sup> (ciliopathy of bile duct epithelia) (OMIM <a href="https://omim.org/entry/619849" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619849</a>)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ GGTP & bile acids; hyperlipidemia</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fibrosis/cirrhosis w/o effect on synthetic function; HSM</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Adapted from Tables 1-<a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_5/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes5">6</a> in <a class="bk_pop" href="#chol-liver-ov.REF.squires.2018.921">Squires & McKiernan [2018]</a></p></div></dd><dt></dt><dd><div><p class="no_margin">ALF = acute liver failure; ALP = alkaline phosphatase; ALT = alanine aminotransferase; ARPKD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> polycystic kidney disease; AST = aspartate aminotransferase; CAKUT = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies of the kidney and urinary tract; CHD = congenital heart disease; DD = developmental delay; ESLD = end-stage liver disease; GGTP = gamma-glutamyl transpeptidase; HCC = hepatocellular carcinoma; HSM = hepatosplenomegaly; HTN = hypertension; INR = international normalized ratio; IUGR = intrauterine growth restriction; MODY5 = maturity-onset diabetes of the young type 5; VLCFA = very long-chain fatty acids</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.3.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="chol-liver-ov.TF.3.2"><p class="no_margin">Link to <i>GeneReview</i> or OMIM entry</p></div></dd><dt>3. </dt><dd><div id="chol-liver-ov.TF.3.3"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.kamal.2018.146">Kamal et al [2018]</a>
|
|
</p></div></dd><dt>4. </dt><dd><div id="chol-liver-ov.TF.3.4"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.leung.2017.s50">Leung & Narkewicz [2017]</a>
|
|
</p></div></dd><dt>5. </dt><dd><div id="chol-liver-ov.TF.3.5"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.grosse.2012.1249">Grosse et al [2012]</a>
|
|
</p></div></dd><dt>6. </dt><dd><div id="chol-liver-ov.TF.3.6"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.girard.2016.1025">Girard et al [2016]</a>
|
|
</p></div></dd><dt>7. </dt><dd><div id="chol-liver-ov.TF.3.7"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.mandato.2019.83">Mandato et al [2019]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.pinon.2019.27">Pinon et al [2019]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.gambella.2023.307">Gambella et al [2023]</a></p></div></dd><dt>8. </dt><dd><div id="chol-liver-ov.TF.3.8"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.saleh.2016.75">Saleh et al [2016]</a>
|
|
</p></div></dd><dt>9. </dt><dd><div id="chol-liver-ov.TF.3.9"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.shneider.2005.634">Shneider & Magid [2005]</a>
|
|
</p></div></dd><dt>10. </dt><dd><div id="chol-liver-ov.TF.3.10"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.lenz.2018.1255">Lenz et al [2018]</a>
|
|
</p></div></dd><dt>11. </dt><dd><div id="chol-liver-ov.TF.3.11"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.gao.2020.1879">Gao et al [2020]</a>
|
|
</p></div></dd><dt>12. </dt><dd><div id="chol-liver-ov.TF.3.12"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.sultan.2018.590">Sultan et al [2018]</a>
|
|
</p></div></dd><dt>13. </dt><dd><div id="chol-liver-ov.TF.3.13"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.grammatikopoulos.2022.473">Grammatikopoulos et al [2022]</a>
|
|
</p></div></dd><dt>14. </dt><dd><div id="chol-liver-ov.TF.3.14"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.david.2020.303">David et al [2020]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.shaheen.2020.2067">Shaheen et al [2020]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.alfadhel.2021.133">Alfadhel et al [2021]</a></p></div></dd><dt>15. </dt><dd><div id="chol-liver-ov.TF.3.15"><p class="no_margin"><a class="bk_pop" href="#chol-liver-ov.REF.goldberg.2020.105">Goldberg & Mack [2020]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.luan.2021.514">Luan et al [2021]</a>, <a class="bk_pop" href="#chol-liver-ov.REF.mandato.2021.179">Mandato et al [2021]</a></p></div></dd></dl></div></div></div></div></div><div id="chol-liver-ov.Evaluation_Strategies_to_I"><h2 id="_chol-liver-ov_Evaluation_Strategies_to_I_">3. Evaluation Strategies to Identify the Cause of a Genetic Cholestatic Liver Disease in a Proband</h2><p>Establishing a specific cause of pediatric genetic cholestatic liver disease:</p><ul><li class="half_rhythm"><div>Can aid in discussions of prognosis (which are beyond the scope of this <i>GeneReview</i>) and <a href="#chol-liver-ov.Genetic_Counseling">genetic counseling</a>;</div></li><li class="half_rhythm"><div>Usually involves a medical history, physical examination, laboratory testing, family history, and <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a>/genetic testing.</div></li></ul><p><b>Family history.</b> A three-generation family history should be taken with attention to relatives with manifestations of a genetic cholestatic liver disease and documentation of relevant findings through direct examination or review of medical records, including results of <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. Because the vast majority of genetic cholestatic liver diseases are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner, the family history may show affected sibs and/or parental <a class="def" href="/books/n/gene/glossary/def-item/consanguinity/">consanguinity</a>. Absence of a known family history does not preclude the diagnosis.</p><p><b>Molecular genetic testing</b> approaches can include <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing (<a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) or comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>). Gene-targeted testing requires that the clinician hypothesize which gene(s) are likely involved, whereas genomic testing does not.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>A cholestatic liver disease <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes some or all of the genes listed in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Tables 1</a>, <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">2</a>, and <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">3</a> is likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. Of note, given the rarity of some of the genes associated with genetic cholestatic liver disease, some panels may not include all the genes mentioned in this overview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
|
|
<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved and may be used if clinical suspicion for a genetic etiology remains high but more targeted investigations have not identified a genetic cause. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul></div><div id="chol-liver-ov.Management"><h2 id="_chol-liver-ov_Management_">4. Management</h2><p>The interventions discussed here focus on symptomatic treatment of clinical manifestations, surveillance issues, and disease-specific treatments/surveillance.</p><div id="chol-liver-ov.Symptomatic_Treatment_of_C"><h3>Symptomatic Treatment of Clinical Manifestations</h3><div id="chol-liver-ov.Nutritional_Supplements"><h4>Nutritional Supplements</h4><p>Standard nutritional approaches for malabsorption of fat and fat-soluble vitamins that benefit growth and development:</p><ul><li class="half_rhythm"><div>Supplementation of the fat-soluble vitamins A, D, E, and K</div></li><li class="half_rhythm"><div>Use of dietary medium-chain triglycerides (MCTs), as they are absorbed independent of bile acids. MCTs can be provided either as infant formula (e.g., Alimentum<sup>®</sup>, Pregestimil<sup>®</sup>) or as MCT oil.</div></li></ul></div><div id="chol-liver-ov.Pruritus__Medical_Manageme"><h4>Pruritus – Medical Management</h4><p>
|
|
<b>Synthetic bile acids</b>
|
|
</p><ul><li class="half_rhythm"><div><b>Oral ursodeoxycholic acid</b> (UDCA), a hydrophilic bile acid, can both replace circulating toxic hydrophobic bile salts and stimulate hepatobiliary secretion of bile salts to improve bile flow. UDCA, which is FDA approved, may be prescribed by physicians for an "off-label" indication in pediatric cholestatic liver disease (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_3/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes3">Table 4</a>).</div></li><li class="half_rhythm"><div><b>Oral cholic acid</b>, available as Cholbam<sup>®</sup>, an FDA-approved bile acid, is specifically used in inborn errors of bile acid synthesis (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_4/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes4">Table 5</a>).</div></li><li class="half_rhythm"><div><b>Glycocholic acid</b> is a bile acid approved as an investigational drug by the FDA for conjugation defects (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_4/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes4">Table 5</a>).</div></li></ul><p>
|
|
<b>Antipruritic agents</b>
|
|
</p><ul><li class="half_rhythm"><div>Cholestyramine binds bile acids in the gut and enhances fecal bile acid secretion</div></li><li class="half_rhythm"><div>Rifaximin is an antibiotic that induces enzymes of drug metabolism to modify and increase excretion of bile salts. Because rifaximin can cause drug-induced hepatitis, its use must be closely monitored [<a class="bk_pop" href="#chol-liver-ov.REF.kriegermeier.2020.149">Kriegermeier & Green 2020</a>].</div></li><li class="half_rhythm"><div>Ileal bile acid transporter inhibitors (IBAT), such as odevixibat or maralixibat, reduce enterohepatic circulation of bile acids by decreasing their reabsorption in the ileum, thus increasing their excretion. Studies have shown that these agents are as effective in treating pruritus and normalizing bile acid levels in certain cholestatic liver diseases, including PFIC and Alagille syndrome [<a class="bk_pop" href="#chol-liver-ov.REF.slavetinsky.2020.e234185">Slavetinsky & Ekkehard 2020</a>].</div></li><li class="half_rhythm"><div>Naloxone, hydroxyzine, and sertraline (which have less well-understood mechanisms of action) may lessen pruritus in some affected individuals [<a class="bk_pop" href="#chol-liver-ov.REF.th_baut.2017.431">Thébaut et al 2017</a>, <a class="bk_pop" href="#chol-liver-ov.REF.squires.2018.921">Squires & McKiernan 2018</a>].</div></li></ul></div><div id="chol-liver-ov.Pruritis__Surgical_Managem"><h4>Pruritis – Surgical Management</h4><p>Surgical management by either <b>partial external biliary diversion</b> (PEBD) or <b>partial ileal exclusion</b> improves pruritus by interrupting the enterohepatic circulation of bile and decreasing bile reabsorption. Both surgical interventions are generally well tolerated and improve pruritus, normalize serum markers of liver disease, and prevent progression of liver disease (by unknown mechanisms). Of note, cirrhosis at the time of surgical intervention is associated with poorer outcomes [<a class="bk_pop" href="#chol-liver-ov.REF.squires.2017.425">Squires et al 2017</a>].</p><p>Although no studies have demonstrated superiority of either of these surgical interventions, the response to PEBD may be longer lasting than the response to ileal exclusion.</p><p><b>Partial external biliary diversion</b> (PEBD), the most common procedure, uses a segment of intestine to form a conduit between the gallbladder and an opening (ostomy) in the abdominal wall. With this approach, the 30%-50% of bile excreted by the liver drains through the ostomy and can be discarded.</p><p>Initially described for children with low-GGTP forms of PFIC, PEBD is associated with an excellent long-term outcome when serum bile acid levels normalize within one year.</p><p>Some data suggest that PEBD is effective in PFIC1 (ATP8B1 deficiency) and mild-to-moderate PFIC2 (BSEP deficiency) in which some enzyme function is retained [<a class="bk_pop" href="#chol-liver-ov.REF.henkel.2019.450">Henkel et al 2019</a>]; however, it may not be effective in severe PFIC2 (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_3/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes3">Table 4</a>). PEBD may also be effective for other forms of cholestasis – namely, Alagille syndrome (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_5/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes5">Table 6</a>).</p><p><b>Partial ileal exclusion,</b> a less utilized approach, uses a loop of small intestine to bypass the terminal ileum, the site of most bile acid reabsorption. Complications of bypassing a portion of the small intestine can include severe malabsorption (particularly of vitamin B<sub>12</sub>) and diarrhea.</p></div><div id="chol-liver-ov.Liver_Transplantation"><h4>Liver Transplantation</h4><p>When the medical and surgical interventions discussed above fail to provide relief from severe pruritus or prevent progression to end-stage liver disease with cirrhosis, liver transplantation often provides a good outcome.</p><p>Note that liver transplantation fails to prevent the extrahepatic complications for any of the disorders described in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Tables 1</a>, <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_1/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes1">2</a>, and <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">3</a>.</p></div></div><div id="chol-liver-ov.Surveillance_Issues"><h3>Surveillance Issues</h3><p><b>Monitoring for complications of chronic liver disease</b> including fibrosis and cirrhosis can be done by abdominal ultrasound examination as a first step. The presence of hepatomegaly and thrombocytopenia has been used to define clinically evident portal hypertension [<a class="bk_pop" href="#chol-liver-ov.REF.bass.2019.763">Bass et al 2019</a>].</p><p><b>Screening for hepatocellular carcinoma (HCC).</b> While HCC can occur in any individual in whom cirrhosis develops, persons with BSEP deficiency (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a>) and <a href="/books/n/gene/alpha1-a/">alpha-1 antitrypsin deficiency</a> are at the highest risk. In those with significant fibrosis or cirrhosis, lifelong screening is warranted with a serum AFP concentration and abdominal ultrasound examination every six to 12 months.</p><p><b>Screening for cholangiocarcinoma.</b> No guidelines have been established.</p></div><div id="chol-liver-ov.DiseaseSpecific_Treatment"><h3>Disease-Specific Treatment of Manifestations</h3><div id="chol-liver-ov.Disorders_of_Transport_of_1"><h4>Disorders of Transport of Bile Acids or Phospholipids</h4><p><a href="#chol-liver-ov.Nutritional_Supplements">Nutritional supplements</a> are often required for disorders of transport of bile acids or phospholipids (see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes">Table 1</a>).</p><p>UDCA (see <a href="#chol-liver-ov.Pruritus__Medical_Manageme">Pruritus -- Medical Management</a>) is also used as a synthetic hydrophilic bile acid replacement in all these disorders.</p><p>The two indications for liver transplantation in these conditions are disease refractory to medical/surgical supportive treatments and progression to end-stage liver disease [<a class="bk_pop" href="#chol-liver-ov.REF.henkel.2019.450">Henkel et al 2019</a>].</p><p>Additional treatment is summarized in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_3/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes3">Table 4</a>.</p><div id="chol-liver-ov.T.pediatric_genetic_choles_3" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Treatment of Manifestations and Surveillance Issues for Disorders of Transport of Bile Acids or Phospholipids</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Pruritus Management</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" style="text-align:left;vertical-align:middle;">Liver Transplantation</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" style="text-align:left;vertical-align:middle;">Surveillance</th></tr><tr><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Rx</th><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biliary diversion <sup>2, 3</sup></th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ABCB4</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC3; MDR3 deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_1" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Rifaximin, cholestyramine, naltrexone, sertraline, odevixibat (IBAT)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">For HCC</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ABCB11</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC2; BSEP deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">+ but less helpful in severe PFIC2</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Anti-BSEP antibodies can occur afterward & cause recurrent disease.</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ATP8B1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/pfic/">ATP8B1 deficiency</a>; PFIC1; Byler syndrome</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Transplant possible, but worsening diarrhea & allograft steatohepatitis are post-transplant complications.</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>KIF12</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">KIF12 deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_1" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Rifaximin, cholestyramine, naltrexone, sertraline</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Case reports [<a class="bk_pop" href="#chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula et al 2019</a>, <a class="bk_pop" href="#chol-liver-ov.REF.stalke.2022.284">Stalke et al 2022</a>]</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>MYOB5</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myosin VB deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+ when pruritus is refractory</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>NR1H4</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC5</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">Not used due to rapid progression to ESLD <sup>4</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TJP2</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PFIC4</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Transplantation possible at younger age due to severity of neonatal disease <sup>4</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For HCC</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>USP53</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">USP53 deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rifaximin more effective than UDCA <sup>5</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_3 hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">BSEP = bile salt export pump; ESLD = end-stage liver disease; HCC = hepatocellular carcinoma; PFIC = progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis; UDCA = ursodeoxycholic acid</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.4.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="chol-liver-ov.TF.4.2"><p class="no_margin">The surgical treatment for pruritus used in most cases is a partial external biliary diversion (PEBD). A partial internal biliary diversion (PIBD) and ileal exclusion have been documented as other methods of surgical treatment of pruritus.</p></div></dd><dt>3. </dt><dd><div id="chol-liver-ov.TF.4.3"><p class="no_margin">PEBD is associated with an excellent long-term outcome when serum bile acid levels normalize within one year.</p></div></dd><dt>4. </dt><dd><div id="chol-liver-ov.TF.4.4"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.henkel.2019.450">Henkel et al [2019]</a>
|
|
</p></div></dd><dt>5. </dt><dd><div id="chol-liver-ov.TF.4.5"><p class="no_margin">
|
|
<a class="bk_pop" href="#chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula et al [2019]</a>
|
|
</p></div></dd></dl></div></div></div></div><div id="chol-liver-ov.Disorders_of_Bile_Acid_Syn_1"><h4>Disorders of Bile Acid Synthesis</h4><p><a href="#chol-liver-ov.Nutritional_Supplements">Nutritional supplements</a> are often required for disorders of bile acid synthesis, since fat-soluble vitamin deficiency is a hallmark of their disease. Additional treatment is summarized in <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_4/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes4">Table 5</a>.</p><div id="chol-liver-ov.T.pediatric_genetic_choles_4" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Treatment of Manifestations and Surveillance Issues for Disorders of Bile Acid Synthesis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment (synthetic bile acids)</th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>AKR1D1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS2</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Cholic acid</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>AMACR</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS4</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>BAAT</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bile acid conjugation defect 1</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Glycocholic acid</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CYP7B1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS3</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chenodeoxycholic acid may be effective.</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CYP27A1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ctx/">Cerebrotendinous xanthomatosis</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Cholic acid</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>HSD3B7</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CBAS1</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CBAS = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> defect in bile acid synthesis</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.5.1"><p class="no_margin">Genes are listed alphabetically</p></div></dd></dl></div></div></div></div><div id="chol-liver-ov.Disorders_with_Cholestatic_1"><h4>Disorders with Cholestatic Liver Disease and Extrahepatic Findings</h4><p>Management of extrahepatic metabolic or developmental manifestations, which typically persist despite treatment of hepatic manifestations, is outside the scope of this overview.</p><p><a href="#chol-liver-ov.Nutritional_Supplements">Nutritional supplements</a> are required. In addition to these supplements, children with cystic fibrosis may benefit from pancreatic enzymes to assist with pancreatic exocrine insufficiency, if present.</p><div id="chol-liver-ov.T.pediatric_genetic_choles_5" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Pediatric Genetic Cholestatic Liver Diseases: Treatment of Manifestations and Surveillance Issues for Disorders with Extrahepatic Metabolic or Developmental Findings</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chol-liver-ov.T.pediatric_genetic_choles_5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s) <sup>1</sup></th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" style="text-align:left;vertical-align:middle;">Synthetic Bile Acids</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Pruritus Management</th><th id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" style="text-align:left;vertical-align:middle;">Liver Transplantation</th></tr><tr><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Rx</th><th headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4" id="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biliary diversion</th></tr></thead><tbody><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CFTR</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/cf/">Cystic fibrosis</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UDCA, but efficacy uncertain</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe loss of hepatic synthetic function or complications of portal HTN</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CLDN1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal ichthyosis-sclerosing cholangitis</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usually UDCA</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For severe progressive liver disease</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>DCDC2</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal sclerosing cholangitis</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="#chol-liver-ov.Pruritus__Medical_Manageme">Antipruritic agents</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For severe, progressive liver disease</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>JAG1</i>
|
|
<br />
|
|
<i>NOTCH2</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/alagille/">Alagille syndrome</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UDCA</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Maralixibat (IBAT)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe loss of hepatic synthetic function, uncontrolled pruritus, or complications of portal HTN <sup>2</sup></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>NPC1</i>
|
|
<br />
|
|
<i>NPC2</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/npc/">Niemann-Pick disease type C</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PEX</i> genes</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/pbd/">Zellweger spectrum disorder</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholic acid</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>PKHD1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/pkd-ar/">Polycystic kidney disease, autosomal recessive</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UDCA used when intrahepatic ductal dilatation is present (i.e., Caroli syndrome).</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe cases: liver transplant or combined renal-hepatic transplant</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SCYL1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cholestasis, acute liver failure, and neurodegeneration</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SERPINA1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/alpha1-a/">Alpha-1 antitrypsin deficiency</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For progressive liver dysfunction / liver failure <sup>3</sup></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC25A13</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal intrahepatic cholestasis caused by citrin deficiency (See <a href="/books/n/gene/citrin/">Citrin Deficiency</a>.)</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver findings typically resolve spontaneously by age 1 yr; liver transplant for severe progressive liver disease</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC51A</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SLC51A deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="#chol-liver-ov.Pruritus__Medical_Manageme">Antipruritic agents</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC51B</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary bile acid malabsorption 2</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="#chol-liver-ov.Pruritus__Medical_Manageme">Antipruritic agents</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TALDO1</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Transadolase 1 deficiency</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver transplant in early, severe cases; higher risk for early-onset HCC</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TTC26</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biliary, renal, neurologic, & skeletal syndrome</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver transplant in severe cases w/fibrosis & cirrhosis</td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>VIPAS39</i> (<i>VIPAR</i>)<br /><i>VPS33B</i></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arthrogryposis, renal dysfunction, & cholestasis <sup>4</sup></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ZFYVE19</i>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ciliopathy of bile duct epithelia</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="#chol-liver-ov.Pruritus__Medical_Manageme">Antipruritic agents</a>
|
|
</td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_4 hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_chol-liver-ov.T.pediatric_genetic_choles_5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">HCC = hepatocellular carcinoma; HTN = hypertension; UDCA = ursodeoxycholic acid</p></div></dd><dt>1. </dt><dd><div id="chol-liver-ov.TF.6.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="chol-liver-ov.TF.6.2"><p class="no_margin">For more detailed information about the clinical manifestations of the liver disease in Alagille syndrome and its management, see Childhood Liver Disease Research Network, <a href="https://childrennetwork.org/Portals/0/Alagille%20Syndrome.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Alagille Syndrome</a> (pdf).</p></div></dd><dt>3. </dt><dd><div id="chol-liver-ov.TF.6.3"><p class="no_margin">For more detailed information about the clinical manifestations of the liver disease in alpha-1 antitrypsin deficiency and its management, see Childhood Liver Disease Research Network, <a href="https://childrennetwork.org/Portals/0/A1AT.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Alpha-1 Antitrypsin Deficiency</a> (pdf).</p></div></dd><dt>4. </dt><dd><div id="chol-liver-ov.TF.6.4"><p class="no_margin">No specific treatment or management of cholestatic liver disease in arthrogryposis, renal dysfunction, and cholestasis has been recommended.</p></div></dd></dl></div></div></div></div></div></div><div id="chol-liver-ov.Genetic_Counseling"><h2 id="_chol-liver-ov_Genetic_Counseling_">5. Genetic Counseling</h2><p>
|
|
<i>Genetic counseling is the process of providing individuals and families with
|
|
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
|
make informed medical and personal decisions. The following section deals with genetic
|
|
risk assessment and the use of family history and genetic testing to clarify genetic
|
|
status for family members; it is not meant to address all personal, cultural, or
|
|
ethical issues that may arise or to substitute for consultation with a genetics
|
|
professional</i>. —ED.</p><div id="chol-liver-ov.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>The vast majority of pediatric genetic primary cholestatic liver diseases are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. Exceptions include <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance of liver disease associated with <i>JAG1</i> or <i>NOTCH2</i> pathogenic variants (i.e., <a href="/books/n/gene/alagille/">Alagille syndrome</a>), autosomal dominant inheritance (in some individuals) of <i>ABCB4</i>-related liver disease (i.e., PFIC3) [<a class="bk_pop" href="#chol-liver-ov.REF.st_ttermayer.2020.651">Stättermayer et al 2020</a>], and autosomal <a class="def" href="/books/n/gene/glossary/def-item/codominant/">codominant</a> inheritance associated with pathogenic variants in <i>SERPINA1</i> (i.e., <a href="/books/n/gene/alpha1-a/">alpha-1 antitrypsin deficiency</a>). Recurrence risk depends on the <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a> associated with the condition.</p><p>Note: If a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a specific genetic disorder or syndrome associated with cholestatic liver disease (e.g., <a href="/books/n/gene/alpha1-a/">alpha-1 antitrypsin deficiency</a> or <a href="/books/n/gene/alagille/">Alagille syndrome</a> [see <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a>]), <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> for that condition is indicated.</p></div><div id="chol-liver-ov.Risk_to_Family_Members_Aut"><h3>Risk to Family Members (Autosomal Recessive Inheritance)</h3><p>
|
|
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
|
</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for one of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li><li class="half_rhythm"><div>Once a molecular diagnosis is established in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> is recommended for the parents of a proband to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> occurred as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the proband or as a <a class="def" href="/books/n/gene/glossary/def-item/postzygotic/">postzygotic</a> <i>de novo</i> event in a mosaic parent [<a class="bk_pop" href="#chol-liver-ov.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> with the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> resulted in homozygosity for the pathogenic variant in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul></li><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> are typically asymptomatic but may rarely manifest related features. Intrahepatic cholestasis of pregnancy has been reported occasionally in mothers of individuals with progressive <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> intrahepatic cholestasis (PFIC).</div></li></ul><p>
|
|
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
|
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of inheriting <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a>, and a 25% chance of inheriting neither of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variants.</div></li><li class="half_rhythm"><div>Heterozygous sibs may be at increased risk for transient neonatal cholestasis. Female sibs who are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a PFIC-associated <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> may be at risk for intrahepatic cholestasis of pregnancy.</div></li></ul><p>
|
|
<b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
|
</p><ul><li class="half_rhythm"><div>Unless an affected individual's reproductive partner also has <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> cholestatic liver disease or is a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, offspring will be obligate heterozygotes for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a><i>.</i></div></li><li class="half_rhythm"><div>Offspring of an affected individual and a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> have a 50% chance of being affected and a 50% chance of being carriers. Higher carrier frequencies have been reported in some populations.</div></li></ul><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a cholestatic liver disease-related <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="chol-liver-ov.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the pathogenic variants in the family.</p></div><div id="chol-liver-ov.Related_Genetic_Counseling"><h3>Related Genetic Counseling Issues</h3><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and of reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="chol-liver-ov.Prenatal_Testing_and_Preim"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the PFIC-causing pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a>. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="chol-liver-ov.Resources"><h2 id="_chol-liver-ov_Resources_">Resources</h2><p>
|
|
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
|
support organizations and/or registries for the benefit of individuals with this disorder
|
|
and their families. GeneReviews is not responsible for the information provided by other
|
|
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
|
<ul><li class="half_rhythm"><div>
|
|
<b>Alagille Syndrome Alliance</b>
|
|
</div><div><b>Phone:</b> 901-286-8869</div><div><b>Email:</b> alagille@alagille.org</div><div>
|
|
<a href="http://www.alagille.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.alagille.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>American Liver Foundation</b>
|
|
</div><div><b>Phone:</b> 800-465-4837 (HelpLine)</div><div>
|
|
<a href="http://www.liverfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">liverfoundation.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Canadian Liver Foundation</b>
|
|
</div><div>Canada</div><div><b>Phone:</b> 800-563-5483</div><div><b>Email:</b> clf@liver.ca</div><div>
|
|
<a href="http://www.liver.ca" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.liver.ca</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Childhood Liver Disease Research Network (ChiLDReN)</b>
|
|
</div><div><b>Phone:</b> 720-777-2598</div><div><b>Email:</b> joan.hines@childrenscolorado.org</div><div>
|
|
<a href="https://childrennetwork.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.childrennetwork.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Children's Liver Disease Foundation</b>
|
|
</div><div>United Kingdom</div><div><b>Phone:</b> +44 (0) 121 212 3839</div><div><b>Email:</b> info@childliverdisease.org</div><div>
|
|
<a href="http://www.childliverdisease.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">childliverdisease.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>PFIC Advocacy and Resource Network, Inc.</b>
|
|
</div><div><b>Email:</b> emily@pfic.org</div><div>
|
|
<a href="https://www.pfic.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.pfic.org</a>
|
|
</div></li></ul>
|
|
</div><div id="chol-liver-ov.Chapter_Notes"><h2 id="_chol-liver-ov_Chapter_Notes_">Chapter Notes</h2><div id="chol-liver-ov.Author_Notes"><h3>Author Notes</h3><p><a href="https://www.pediatrics.pitt.edu/people/james-e-squires-md-ms" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">James E Squires, MD, MS</a>, joined the faculty at the Children's Hospital of Pittsburgh in 2015, where he is an associate professor in pediatrics, director of the pediatric advanced/transplant hepatology fellowship, and associate medical director of hepatology. Dr Squires remains active in both clinical and research pursuits. He is a co-investigator in the <a href="https://childrennetwork.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Childhood Liver Disease Research Network</a> (ChiLDReN), an NIH-funded consortium working to improve the lives of children with rare cholestatic liver diseases. He is also a member of the Society of Pediatric Liver Transplant (SPLIT), a multifaceted organization focused on improving outcomes for children receiving liver transplantation. He is the clinical lead for the Starzl Network for Excellence in Liver Transplantation, a novel learning health network of leading pediatric transplant institutions committed to continuous improvement until every child can achieve a long and healthy life, with funding from the Patient-Centered Outcomes Research Institute (PCORI) to advance this work. Other current interests include metabolic liver disease, acute liver failure, and liver transplant.</p></div><div id="chol-liver-ov.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>25 May 2023 (aa) Revision: <i>HNF1B</i> added to <a href="/books/NBK584020/table/chol-liver-ov.T.pediatric_genetic_choles_2/?report=objectonly" target="object" rid-ob="figobcholliverovTpediatricgeneticcholes2">Table 3</a></div></li><li class="half_rhythm"><div>15 September 2022 (bp) Review posted live</div></li><li class="half_rhythm"><div>9 December 2021 (js) Original submission</div></li></ul></div></div><div id="chol-liver-ov.References"><h2 id="_chol-liver-ov_References_">References</h2><div id="chol-liver-ov.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.alfadhel.2021.133">Alfadhel
|
|
M, Umair
|
|
M, Almuzzain
|
|
B, Asiri
|
|
A, Al Tuwaijri
|
|
A, Alhamoudi
|
|
K, Alyafee
|
|
Y, Al-Owain
|
|
M.
|
|
Identification of the TTC26 splice variant in a novel complex ciliopathy syndrome with biliary, renal, neurological, and skeletal manifestations.
|
|
Mol Syndromol.
|
|
2021;12:133-40.
|
|
[<a href="/pmc/articles/PMC8215951/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8215951</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34177428" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34177428</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.alhebbi.2021.151">Alhebbi
|
|
H, Peer-Zada
|
|
AA, Al-Hussaini
|
|
AA, Algubaisi
|
|
S, Albassami
|
|
A, AlMasri
|
|
N, Alrusayni
|
|
Y, Alruzug
|
|
IM, Alharby
|
|
E, Samman
|
|
MA, Ayoub
|
|
SZ, Maddirevula
|
|
S, Peake
|
|
RWA, Alkuraya
|
|
FS, Wali
|
|
S, Almontashiri
|
|
NAM. New paradigms of USP53 disease: normal GGT cholestasis, BRIC, cholangiopathy, and responsiveness to rifampicin.
|
|
J Hum Genet.
|
|
2021;66:151-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32759993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32759993</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.bass.2019.763">Bass
|
|
LM, Shneider
|
|
BL, Henn
|
|
L, Goodrich
|
|
NP, Magee
|
|
JC, et al.
|
|
Clinically evident portal hypertension: an operational research definition for future investigations in the pediatric population.
|
|
J Pediatr Gastroenterol Nutr.
|
|
2019;68:763-7.
|
|
[<a href="/pmc/articles/PMC6534459/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6534459</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30908382" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30908382</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.biesecker.2021.8">Biesecker
|
|
LG, Adam
|
|
MP, Alkuraya
|
|
FS, Amemiya
|
|
AR, Bamshad
|
|
MJ, Beck
|
|
AE, Bennett
|
|
JT, Bird
|
|
LM, Carey
|
|
JC, Chung
|
|
B, Clark
|
|
RD, Cox
|
|
TC, Curry
|
|
C, Dinulos
|
|
MBP, Dobyns
|
|
WB, Giampietro
|
|
PF, Girisha
|
|
KM, Glass
|
|
IA, Graham
|
|
JM
|
|
Jr, Gripp
|
|
KW, Haldeman-Englert
|
|
CR, Hall
|
|
BD, Innes
|
|
AM, Kalish
|
|
JM, Keppler-Noreuil
|
|
KM, Kosaki
|
|
K, Kozel
|
|
BA, Mirzaa
|
|
GM, Mulvihill
|
|
JJ, Nowaczyk
|
|
MJM, Pagon
|
|
RA, Retterer
|
|
K, Rope
|
|
AF, Sanchez-Lara
|
|
PA, Seaver
|
|
LH, Shieh
|
|
JT, Slavotinek
|
|
AM, Sobering
|
|
AK, Stevens
|
|
CA, Stevenson
|
|
DA, Tan
|
|
TY, Tan
|
|
WH, Tsai
|
|
AC, Weaver
|
|
DD, Williams
|
|
MS, Zackai
|
|
E, Zarate
|
|
YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics.
|
|
Am J Hum Genet.
|
|
2021;108:8-15.
|
|
[<a href="/pmc/articles/PMC7820621/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7820621</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33417889" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33417889</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.bull.2021.667">Bull
|
|
LN, Ellmers
|
|
R, Foskett
|
|
P, Strautnieks
|
|
S, Sambrotta
|
|
M, Czubkowski
|
|
P, Jankowska
|
|
I, Wagner
|
|
B, Deheragoda
|
|
M, Thompson
|
|
RJ. Cholestasis due to USP53 deficiency.
|
|
J Pediatr Gastroenterol Nutr.
|
|
2021;72:667-73.
|
|
[<a href="/pmc/articles/PMC8549450/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8549450</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33075013" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33075013</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.carlton.2003.91">Carlton
|
|
VE, Harris
|
|
BZ, Puffenberger
|
|
EG, Batta
|
|
AK, Knisely
|
|
AS, Robinson
|
|
DL, Strauss
|
|
KA, Shneider
|
|
BL, Lim
|
|
WA, Salen
|
|
G, Morton
|
|
DH, Bull
|
|
LN. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT.
|
|
Nat Genet.
|
|
2003;34:91-6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12704386" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12704386</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.clayton.1969.112">Clayton
|
|
RJ, Iber
|
|
FL, Ruebner
|
|
BH, McKusick
|
|
VA. Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred.
|
|
Am J Dis Child.
|
|
1969;117:112-24.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/5762004" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5762004</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.david.2020.303">David
|
|
O, Eskin-Schwartz
|
|
M, Ling
|
|
G, Dolgin
|
|
V, Kristal
|
|
E, Benkowitz
|
|
E, Osyntsov
|
|
L, Gradstein
|
|
L, Birk, OS, Loewenthal
|
|
N, Yerushalmi
|
|
B. Pituitary stalk interruption syndrome broadens the clinical spectrum of the TTC26 ciliopathy.
|
|
Clin Genet.
|
|
2020;98:303-7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32617964" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32617964</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.fawaz.2017.154">Fawaz
|
|
R, Baumann
|
|
U, Ekong
|
|
U, Fischler
|
|
B, Hadzic
|
|
N, Mack
|
|
CL, McLin
|
|
VA, Molleston
|
|
JP, Neimark
|
|
E, Ng
|
|
VL, Karpen
|
|
SJ. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition.
|
|
J Pediatr Gastroenterol Nutr.
|
|
2017;64:154-68.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27429428" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27429428</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.feldman.2019.346">Feldman
|
|
AG, Sokol
|
|
RJ. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics.
|
|
Nat Rev Gastroenterol Hepatol.
|
|
2019;16:346-60.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30903105" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30903105</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.gambella.2023.307">Gambella
|
|
A, Kalantari
|
|
S, Cadamuro
|
|
M, Quaglia
|
|
M, Delvecchio
|
|
M, Fabris
|
|
L, Pinon
|
|
M.
|
|
The landscape of HNF1B deficiency: a syndrome not yet fully explored.
|
|
Cells.
|
|
2023;12:307.
|
|
[<a href="/pmc/articles/PMC9856658/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9856658</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36672242" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36672242</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.gao.2020.1879">Gao
|
|
E, Cheema
|
|
H, Waheed
|
|
N, Mushtaq
|
|
I, Erden
|
|
N, Nelson-Williams
|
|
C, Jain
|
|
D, Soroka
|
|
CJ, Boyer
|
|
JL, Khalil
|
|
Y, Clayton
|
|
PT, Mistry
|
|
PK, Lifton
|
|
RP, Vilarinho
|
|
S. Organic solute transporter alpha deficiency: a disorder with cholestasis, liver fibrosis, and congenital diarrhea.
|
|
Hepatology.
|
|
2020;71:1879-82.
|
|
[<a href="/pmc/articles/PMC8577800/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8577800</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31863603" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31863603</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.girard.2016.1025">Girard
|
|
M, Bizet
|
|
AA, Lachaux
|
|
A, Gonzales
|
|
E, Filhol
|
|
E, Collardeau-Frachon
|
|
S, Jeanpierre
|
|
C, Henry
|
|
C, Fabre
|
|
M, Viremouneix
|
|
L, Galmiche
|
|
L, Debray
|
|
D, Bole-Feysot
|
|
C, Nitschke
|
|
P, Pariente
|
|
D, Guettier
|
|
C, Lyonnet
|
|
S, Heidet
|
|
L, Bertholet
|
|
A, Jacquemin
|
|
E, Henrion-Caude
|
|
A, Saunier
|
|
S. DCDC2 mutations cause neonatal sclerosing cholangitis.
|
|
Hum Mutat.
|
|
2016;37:1025-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27319779" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27319779</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.goldberg.2020.105">Goldberg
|
|
A, Mack
|
|
CL. Inherited cholestatic diseases in the era of personalized medicine.
|
|
Clin Liver Dis (Hoboken). 2020;15:105-9.
|
|
[<a href="/pmc/articles/PMC7128029/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7128029</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32257121" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32257121</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.gong.2017.561">Gong
|
|
JY, Setchell
|
|
KDR, Zhao
|
|
J, Zhang
|
|
W, Wolfe
|
|
B, Lu
|
|
Y, Lackner
|
|
K, Knisely
|
|
AS, Wang
|
|
NL, Hao
|
|
CZ, Zhang
|
|
MH, Wang
|
|
JS. Severe neonatal cholestasis in cerebrotendinous xanthomatosis: genetics, immunostaining, mass spectrometry.
|
|
J Pediatr Gastroenterol Nutr
|
|
2017;65:561-8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28937538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28937538</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.gonzales.2017.164">Gonzales
|
|
E, Taylor
|
|
SA, Davit-Spraul
|
|
A, Thébaut
|
|
A, Thomassin
|
|
N, Guettier
|
|
C, Whitington
|
|
PF, Jacquemin
|
|
E. MYO5B mutations cause cholestasis with normal serum gamma-glutamyl transferase activity in children without microvillus inclusion disease.
|
|
Hepatology
|
|
2017;65:164-73.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27532546" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27532546</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.grammatikopoulos.2022.473">Grammatikopoulos
|
|
T, Hadzic
|
|
N, Foskett
|
|
P, Strautnieks
|
|
S, Samyn
|
|
M, Vara
|
|
R, Dhawan
|
|
A, Hertecant
|
|
J, Al Jasmi
|
|
F, Rahman
|
|
O, Deheragoda
|
|
M, Bull
|
|
LN, Thompson
|
|
RJ, et al.
|
|
Liver disease and risk of hepatocellular carcinoma in children with mutations in TALDO1.
|
|
Hepatol Commun.
|
|
2022;6:473-9
|
|
[<a href="/pmc/articles/PMC8870026/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8870026</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34677006" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34677006</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.grosse.2012.1249">Grosse
|
|
B, Cassio
|
|
D, Yousef
|
|
N, Bernando
|
|
C, Jacquemin
|
|
E, Gonzales
|
|
E.
|
|
Claudin-1 involved in neonatal ichthyosis sclerosing cholangitis syndrome regulates hepatic paracellular permeability.
|
|
Hepatology.
|
|
2012;55: 1249-59.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22030598" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22030598</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.harpavat.2016.605">Harpavat
|
|
S, Garcia-Prats
|
|
JA, Shneider
|
|
BL. Newborn bilirubin screening for biliary atresia.
|
|
N Engl J Med.
|
|
2016;375:605-6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27509119" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27509119</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.henkel.2019.450">Henkel
|
|
SAF, Squires
|
|
JH, Ayers
|
|
M, Ganoza
|
|
A, McKiernan
|
|
P, Squires
|
|
JE. Expanding etiology of progressive familial intrahepatic cholestasis.
|
|
World J Hepatol.
|
|
2019;11:450-63.
|
|
[<a href="/pmc/articles/PMC6547292/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6547292</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31183005" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31183005</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.heubi.2007.282">Heubi
|
|
JE, Setchell
|
|
KD, Bove
|
|
KE. Inborn errors of bile acid metabolism.
|
|
Semin. Liver Dis
|
|
2007;27:282-94.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17682975" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17682975</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.j_nsson.2017.519">Jónsson
|
|
H, Sulem
|
|
P, Kehr
|
|
B, Kristmundsdottir
|
|
S, Zink
|
|
F, Hjartarson
|
|
E, Hardarson
|
|
MT, Hjorleifsson
|
|
KE, Eggertsson
|
|
HP, Gudjonsson
|
|
SA, Ward
|
|
LD, Arnadottir
|
|
GA, Helgason
|
|
EA, Helgason
|
|
H, Gylfason
|
|
A, Jonasdottir
|
|
A, Jonasdottir
|
|
A, Rafnar
|
|
T, Frigge
|
|
M, Stacey
|
|
SN, Th Magnusson
|
|
O, Thorsteinsdottir
|
|
U, Masson
|
|
G, Kong
|
|
A, Halldorsson
|
|
BV, Helgason
|
|
A, Gudbjartsson
|
|
DF, Stefansson
|
|
K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland.
|
|
Nature.
|
|
2017;549:519-22.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.kamal.2018.146">Kamal
|
|
N, Surana
|
|
P, Koh
|
|
C. Liver disease in patients with cystic fibrosis.
|
|
Curr Opin Gastroenterol.
|
|
2018;34:146-51.
|
|
[<a href="/pmc/articles/PMC7232742/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7232742</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29438119" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29438119</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.karpen.2020.115">Karpen
|
|
SJ. Pediatric cholestasis: epidemiology, genetics, diagnosis, and current management.
|
|
Clin Liver Dis (Hoboken). 2020;15:115-19.
|
|
[<a href="/pmc/articles/PMC7346681/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7346681</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32685137" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32685137</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.klomp.2000.1337">Klomp
|
|
LWJ, Bull
|
|
LN, Knisley
|
|
AS, Van Der Doelen
|
|
MA, Juijn
|
|
JA, Berger
|
|
R, Forget
|
|
S, Nieslen
|
|
IM, Eiberg
|
|
H, Houwen
|
|
RH. A missense mutation in FIC1 is associated with Greenland Familial Cholestasis.
|
|
Hepatology
|
|
2000;32:1337-41.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11093741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11093741</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.kriegermeier.2020.149">Kriegermeier
|
|
A, Green
|
|
R. Pediatric cholestatic liver disease: review of bile acid metabolism and discussion of current and emerging therapies.
|
|
Front Med (Lausanne). 2020;7:149.
|
|
[<a href="/pmc/articles/PMC7214672/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7214672</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32432119" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32432119</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.lenz.2018.1255">Lenz
|
|
D, McClean
|
|
P, Kansu
|
|
A, Bonnen
|
|
PE, Ranucci
|
|
G, Thiel
|
|
C, Straub
|
|
BK, Harting
|
|
I, Alhaddad
|
|
B, Dimitrov
|
|
B, Kotzaeridou
|
|
U, Wenning
|
|
D, Iorio
|
|
R, Himes
|
|
RW, Kuloğlu
|
|
Z, Blakely
|
|
EL, Taylor
|
|
RW, Meitinger
|
|
T, Kölker
|
|
S, Prokisch
|
|
H, Hoffmann
|
|
GF, Haack
|
|
TB, Staufner
|
|
C. SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).
|
|
Genet Med.
|
|
2018;20:1255-65.
|
|
[<a href="/pmc/articles/PMC5989927/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5989927</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29419818" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29419818</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.leung.2017.s50">Leung
|
|
DH, Narkewicz
|
|
MR. Cystic fibrosis-related cirrhosis.
|
|
J Cyst Fibros.
|
|
2017;16:S50-61.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28986027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28986027</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.luan.2021.514">Luan
|
|
W, Hao
|
|
CZ, Li
|
|
JQ, Wei
|
|
Q, Gong
|
|
JY, Qiu
|
|
YL, Lu
|
|
Y, Shen
|
|
CH, Xia
|
|
Q, Xie
|
|
XB, Zhang
|
|
MH, Abuduxikuer
|
|
K, Li
|
|
ZD, Wang
|
|
L, Xing
|
|
QH, Knisely
|
|
AS, Wang
|
|
JS. Biallelic loss-of-function ZFYVE19 mutations are associated with congenital hepatic fibrosis, sclerosing cholangiopathy and high-GGT cholestasis.
|
|
J Med Genet.
|
|
2021;58:514-25.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32737136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32737136</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.maddirevula.2019.1164">Maddirevula
|
|
S, Alhebbi
|
|
H, Alqahtani
|
|
A, Algoufi
|
|
T, Alsaif
|
|
HS, Ibrahim
|
|
N, Abdulwahab
|
|
F, Barr
|
|
M, Alzaidan
|
|
H, Almehaideb
|
|
A, AlSasi
|
|
O, Alhashem
|
|
A, Hussaini
|
|
HA, Wali
|
|
S, Alkuraya
|
|
FS. Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants.
|
|
Genet Med.
|
|
2019;21:1164-72.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30250217" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30250217</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.mandato.2021.179">Mandato
|
|
C, Siano
|
|
MA, Nazzaro
|
|
L, Gelzo
|
|
M, Francalanci
|
|
P, Rizzo
|
|
F, D'Agostino
|
|
Y, Morleo
|
|
M, Brillante
|
|
S, Weisz
|
|
A, Franco
|
|
B, Vajro
|
|
P. A
|
|
ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant.
|
|
Orphanet J Rare Dis.
|
|
2021;16:179.
|
|
[<a href="/pmc/articles/PMC8048179/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8048179</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33853651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33853651</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.mandato.2019.83">Mandato
|
|
C, Zollo
|
|
G, Vajro
|
|
P. Cholestatic jaundice in infancy: struggling with many old and new phenotypes.
|
|
Ital J Pediatr.
|
|
2019;45:83.
|
|
[<a href="/pmc/articles/PMC6637514/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6637514</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31315650" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31315650</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.pinon.2019.27">Pinon
|
|
M, Carboni
|
|
M, Colavito
|
|
D, Cisarò
|
|
F, Peruzzi
|
|
L, Pizzol
|
|
A, Calosso
|
|
G, David
|
|
E, Calvo
|
|
PL. Not only Alagille syndrome. Syndromic paucity of interlobular bile ducts secondary to HNF1β deficiency: a case report and literature review.
|
|
Ital J Pediatr.
|
|
2019;45:27.
|
|
[<a href="/pmc/articles/PMC6385394/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6385394</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30791938" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30791938</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.saleh.2016.75">Saleh
|
|
M, Kamath
|
|
BM, Chitayat
|
|
D. Alagille syndrome: clinical perspectives.
|
|
Appl Clin Genet
|
|
2016;9:75-82.
|
|
[<a href="/pmc/articles/PMC4935120/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4935120</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27418850" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27418850</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.setchell.2013.945">Setchell
|
|
KD, Heubi
|
|
JE, Shah
|
|
S, Lavine
|
|
JE, Suskind
|
|
D, Al-Edressi
|
|
M, Potter
|
|
C, Russell
|
|
DW, O’Connell
|
|
NC, Wolfe
|
|
B, Jha
|
|
P, Zhang
|
|
W, Bove
|
|
KE, Knisely
|
|
AS, Hofmann
|
|
AF, Rosenthal
|
|
P, Bull
|
|
LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency.
|
|
Gastroenterology.
|
|
2013;144:945-955.e6.
|
|
[<a href="/pmc/articles/PMC4175397/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4175397</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23415802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23415802</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.shaheen.2020.2067">Shaheen
|
|
R, Alsahli
|
|
S, Ewida
|
|
N, Alzahrani
|
|
F, Shamseldin
|
|
HE, Patel
|
|
N, Al Qahtani
|
|
A, Alhebbi
|
|
H, Alhashem
|
|
A, Al-Sheddi
|
|
T, Alomar
|
|
R, Alobeid
|
|
E, Abouelhoda
|
|
M, Monies
|
|
D, Al-Hussaini
|
|
A, Alzouman
|
|
MA, Shagrani
|
|
M, Faqeih
|
|
E, Alkuraya
|
|
FS. Biallelic mutations in tetratricopeptide repeat domain 26 (intraflagellar transport 56) cause severe biliary ciliopathy in humans.
|
|
Hepatology.
|
|
2020;71:2067-79.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/31595528" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31595528</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.shneider.2005.634">Shneider
|
|
BL, Magid
|
|
MS. Liver disease in autosomal recessive polycystic kidney disease.
|
|
Pediatr Transplant.
|
|
2005;9:634-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16176423" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16176423</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.slavetinsky.2020.e234185">Slavetinsky
|
|
C, Ekkehard
|
|
S. Odevixibat and partial external biliary diversion showed equal improvement of cholestasis in a patient with progressive familial intrahepatic cholestasis.
|
|
BMJ Case Rep.
|
|
2020;13:e234185.
|
|
[<a href="/pmc/articles/PMC7326258/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7326258</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32601135" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32601135</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.squires.2017.425">Squires
|
|
JE, Celik
|
|
N, Morris
|
|
A, Soltys
|
|
K, Mazaeriegos
|
|
G, Shneider. B, Squires
|
|
RH. Clinical variability after partial external biliary diversion in familial intrahepatic cholestasis 1 deficiency.
|
|
J Pediatr Gastroenterol Nutr.
|
|
2017;64:425-30.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28045770" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28045770</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.squires.2018.921">Squires
|
|
JE, McKiernan
|
|
P. Molecular mechanisms in pediatric cholestasis.
|
|
Gastroenterol Clin North Am.
|
|
2018;47:921-37.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30337041" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30337041</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.squires.2021.641">Squires
|
|
RH, Monga
|
|
SP. Progressive familial intrahepatic cholestasis: is it time to transition to genetic cholestasis?
|
|
J Pediatr Gastroenterol Nutr.
|
|
2021;72:641-3.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/33661247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33661247</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.stalke.2022.284">Stalke
|
|
A, Sgodda
|
|
M, Cantz
|
|
T, Skawran
|
|
B, Lainka
|
|
E, Hartleben
|
|
B, Baumann
|
|
U, Pfister
|
|
ED. KIF12 variants and disturbed hepatocyte polarity in children with a phenotypic spectrum of cholestatic liver disease.
|
|
J Pediatr.
|
|
2022;240:284-291.e9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/34555379" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34555379</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.st_ttermayer.2020.651">Stättermayer
|
|
AF, Halilbasic
|
|
E, Wrba
|
|
F, Ferenci
|
|
P, Trauner
|
|
M. Variants in ABCB4 (MDR3) across the spectrum of cholestatic liver diseases in adults.
|
|
J Hepatol.
|
|
2020;73:651-63.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32376413" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32376413</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.sultan.2018.590">Sultan
|
|
M, Rao
|
|
A, Elpeleg
|
|
O, Vaz
|
|
FM, Abu-Libdeh
|
|
B, Karpen
|
|
SJ, Dawson
|
|
PA. Organic solute transporter-β (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis.
|
|
Hepatology.
|
|
2018;68:590-8.
|
|
[<a href="/pmc/articles/PMC5847420/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5847420</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28898457" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28898457</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.th_baut.2017.431">Thébaut
|
|
A, Habes
|
|
D, Gottrand
|
|
F, Rivet
|
|
C, Cohen
|
|
J, Debray
|
|
D, Jacquemin
|
|
E, Gonzales
|
|
E. Sertraline as an additional treatment for cholestatic pruritus in children.
|
|
J Pediatr Gastroenterol Nutr.
|
|
2017;64:431-5.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27557426" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27557426</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.uehara.2020.251">Uehara
|
|
T, Yamada
|
|
M, Umetsu
|
|
S, Nittono
|
|
H, Suzuki
|
|
H, Fujisawa
|
|
T, Takenouchi
|
|
T, Inui
|
|
A, Kosaki
|
|
K. Biallelic mutations in the LSR gene cause a novel type of infantile intrahepatic cholestasis.
|
|
J Pediatr.
|
|
2020;221:251-4.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32303357" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32303357</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="chol-liver-ov.REF.zhang.2020.1142">Zhang
|
|
J, Yang
|
|
Y, Gong
|
|
JY, Li
|
|
LT, Li
|
|
JQ, Zhang
|
|
MH, Lu
|
|
Y, Xie
|
|
XB, Hong
|
|
YR, Yu
|
|
Z, Knisely
|
|
AS, Wang
|
|
JS. Low-GGT intrahepatic cholestasis associated with biallelic USP53 variants: clinical, histological and ultrastructural characterization.
|
|
Liver Int.
|
|
2020;40:1142-50.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32124521" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32124521</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
|
|
<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
|
|
a registered trademark of the University of Washington, Seattle. All rights
|
|
reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
|
|
hereby granted to reproduce, distribute, and translate copies of content materials for
|
|
noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
|
|
Washington) are included with each copy; (ii) a link to the original material is provided
|
|
whenever the material is published elsewhere on the Web; and (iii) reproducers,
|
|
distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
|
|
of GeneReviews chapters for use in lab reports and clinic notes are a permitted
|
|
use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
|
|
contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div><div class="small"><span class="label">Bookshelf ID: NBK584020</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/36108118" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">36108118</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/parkinson-overview/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/pmld1/" title="Next page in this title">Next ></a></div></div></div></div>
|
|
|
|
</div>
|
|
|
|
<!-- Custom content below content -->
|
|
<div class="col4">
|
|
|
|
</div>
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<!-- Custom contetnt below bottom nav -->
|
|
<div class="col5">
|
|
|
|
</div>
|
|
</div>
|
|
|
|
<div id="rightcolumn" class="four_col col last">
|
|
<!-- Custom content above discovery portlets -->
|
|
<div class="col6">
|
|
<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK584020&db=books">Share</a></div>
|
|
|
|
</div>
|
|
<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK584020/?report=reader">PubReader</a></li><li><a href="/books/NBK584020/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK584020" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK584020" style="display:none" title="Cite this Page"><div class="bk_tt">Amendola M, Squires JE. Pediatric Genetic Cholestatic Liver Disease Overview. 2022 Sep 15 [Updated 2023 May 25]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK584020/pdf/Bookshelf_NBK584020.pdf">PDF version of this page</a> (553K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#chol-liver-ov.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#chol-liver-ov.Clinical_Characteristics_o" ref="log$=inpage&link_id=inpage"> Clinical Characteristics of Genetic Cholestatic Liver Disease</a></li><li><a href="#chol-liver-ov.Causes_of_Genetic_Cholesta" ref="log$=inpage&link_id=inpage"> Causes of Genetic Cholestatic Liver Disease</a></li><li><a href="#chol-liver-ov.Evaluation_Strategies_to_I" ref="log$=inpage&link_id=inpage"> Evaluation Strategies to Identify the Cause of a Genetic Cholestatic Liver Disease in a Proband</a></li><li><a href="#chol-liver-ov.Management" ref="log$=inpage&link_id=inpage"> Management</a></li><li><a href="#chol-liver-ov.Genetic_Counseling" ref="log$=inpage&link_id=inpage"> Genetic Counseling</a></li><li><a href="#chol-liver-ov.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#chol-liver-ov.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#chol-liver-ov.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=5244[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">ABCB4</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=54532[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">USP53</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=9971[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">NR1H4</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=113220[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">KIF12</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=6718[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">AKR1D1</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=8647[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">ABCB11</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=80270[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">HSD3B7</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=9420[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">CYP7B1</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=570[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">BAAT</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=23600[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">AMACR</a>
|
|
</li><li>
|
|
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=5205[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">ATP8B1</a>
|
|
</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=5363526" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=5363526" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301474" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> ATP8B1 Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> ATP8B1 Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bull LN, Morotti R, Squires JE. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301409" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Isolated Methylmalonic Acidemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Isolated Methylmalonic Acidemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Manoli I, Sloan JL, Venditti CP. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301495" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Maple Syrup Urine Disease.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Maple Syrup Urine Disease.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Strauss KA, Puffenberger EG, Carson VJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301715" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hereditary Paraganglioma-Pheochromocytoma Syndromes.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hereditary Paraganglioma-Pheochromocytoma Syndromes.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Else T, Greenberg S, Fishbein L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301551" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sickle Cell Disease.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sickle Cell Disease.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bender MA, Carlberg K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=36108118" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=36108118" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d502cbcde49f3df76b0115">Pediatric Genetic Cholestatic Liver Disease Overview - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Pediatric Genetic Cholestatic Liver Disease Overview - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d502c984f3725e59c91401">Table 5. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Table 5. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d502c984f3725e59c90d5c">Table 4. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Table 4. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d502c867c23b31e04366c6">Table 6. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Table 6. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d502c767c23b31e0436358">Table 2. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Table 2. [Pediatric Genetic Cholestatic Liver Diseases:...]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
|
|
|
|
<!-- Custom content below discovery portlets -->
|
|
<div class="col7">
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
<!-- Custom content after all -->
|
|
<div class="col8">
|
|
|
|
</div>
|
|
<div class="col9">
|
|
|
|
</div>
|
|
|
|
<script type="text/javascript" src="/corehtml/pmc/js/jquery.scrollTo-1.4.2.js"></script>
|
|
<script type="text/javascript">
|
|
(function($){
|
|
$('.skiplink').each(function(i, item){
|
|
var href = $($(item).attr('href'));
|
|
href.attr('tabindex', '-1').addClass('skiptarget'); // ensure the target can receive focus
|
|
$(item).on('click', function(event){
|
|
event.preventDefault();
|
|
$.scrollTo(href, 0, {
|
|
onAfter: function(){
|
|
href.focus();
|
|
}
|
|
});
|
|
});
|
|
});
|
|
})(jQuery);
|
|
</script>
|
|
</div>
|
|
<div class="bottom">
|
|
<script type="text/javascript">
|
|
var PBooksSearchTermData = {
|
|
highlighter: "bold",
|
|
dateTime: "03/15/2025 00:30:27",
|
|
terms: [
|
|
'2', 'autosomal', 'autosomal recessive juvenile parkinson disease', 'disease', 'disorders', 'juvenile', 'parkinson', 'parkinsonian', 'parkinsonian disorders', 'parkinsonian disorders', 'parkinsonian disorders', 'practice guideline', 'recessive'
|
|
]
|
|
};
|
|
</script>
|
|
<div id="NCBIFooter_dynamic">
|
|
<!--<component id="Breadcrumbs" label="breadcrumbs"/>
|
|
<component id="Breadcrumbs" label="helpdesk"/>-->
|
|
|
|
</div>
|
|
|
|
<div class="footer" id="footer">
|
|
<section class="icon-section">
|
|
<div id="icon-section-header" class="icon-section_header">Follow NCBI</div>
|
|
<div class="grid-container container">
|
|
<div class="icon-section_container">
|
|
<a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
|
<defs>
|
|
<style>
|
|
.cls-11 {
|
|
fill: #737373;
|
|
}
|
|
</style>
|
|
</defs>
|
|
<title>Twitter</title>
|
|
<path class="cls-11" d="M250.11,105.48c-7,3.14-13,3.25-19.27.14,8.12-4.86,8.49-8.27,11.43-17.46a78.8,78.8,0,0,1-25,9.55,39.35,39.35,0,0,0-67,35.85,111.6,111.6,0,0,1-81-41.08A39.37,39.37,0,0,0,81.47,145a39.08,39.08,0,0,1-17.8-4.92c0,.17,0,.33,0,.5a39.32,39.32,0,0,0,31.53,38.54,39.26,39.26,0,0,1-17.75.68,39.37,39.37,0,0,0,36.72,27.3A79.07,79.07,0,0,1,56,223.34,111.31,111.31,0,0,0,116.22,241c72.3,0,111.83-59.9,111.83-111.84,0-1.71,0-3.4-.1-5.09C235.62,118.54,244.84,113.37,250.11,105.48Z">
|
|
</path>
|
|
</svg></a>
|
|
<a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
|
<title>Facebook</title>
|
|
<path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z">
|
|
</path>
|
|
</svg></a>
|
|
<a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
|
<title>LinkedIn</title>
|
|
<path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z">
|
|
</path>
|
|
</svg></a>
|
|
<a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
|
<defs>
|
|
<style>
|
|
.cls-11,
|
|
.cls-12 {
|
|
fill: #737373;
|
|
}
|
|
|
|
.cls-11 {
|
|
fill-rule: evenodd;
|
|
}
|
|
</style>
|
|
</defs>
|
|
<title>GitHub</title>
|
|
<path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z">
|
|
</path>
|
|
<path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1">
|
|
</path>
|
|
<path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08">
|
|
</path>
|
|
<path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path>
|
|
<path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0">
|
|
</path>
|
|
<path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0">
|
|
</path>
|
|
<path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0">
|
|
</path>
|
|
<path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path>
|
|
</svg></a>
|
|
<a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog">
|
|
<svg xmlns="http://www.w3.org/2000/svg" id="Layer_1" data-name="Layer 1" viewBox="0 0 40 40">
|
|
<defs><style>.cls-1{fill:#737373;}</style></defs>
|
|
<title>NCBI Insights Blog</title>
|
|
<path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"></path>
|
|
</svg>
|
|
</a>
|
|
</div>
|
|
</div>
|
|
</section>
|
|
|
|
<section class="container-fluid bg-primary">
|
|
<div class="container pt-5">
|
|
<div class="row mt-3">
|
|
<div class="col-lg-3 col-12">
|
|
<p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p>
|
|
<ul class="list-inline social_media">
|
|
<li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
|
<style type="text/css">
|
|
.st20 {
|
|
fill: #FFFFFF;
|
|
}
|
|
|
|
.st30 {
|
|
fill: none;
|
|
stroke: #FFFFFF;
|
|
stroke-width: 8;
|
|
stroke-miterlimit: 10;
|
|
}
|
|
</style>
|
|
<title>Twitter</title>
|
|
<g>
|
|
<g>
|
|
<g>
|
|
<path class="st20" d="M192.9,88.1c-5,2.2-9.2,2.3-13.6,0.1c5.7-3.4,6-5.8,8.1-12.3c-5.4,3.2-11.4,5.5-17.6,6.7 c-10.5-11.2-28.1-11.7-39.2-1.2c-7.2,6.8-10.2,16.9-8,26.5c-22.3-1.1-43.1-11.7-57.2-29C58,91.6,61.8,107.9,74,116 c-4.4-0.1-8.7-1.3-12.6-3.4c0,0.1,0,0.2,0,0.4c0,13.2,9.3,24.6,22.3,27.2c-4.1,1.1-8.4,1.3-12.5,0.5c3.6,11.3,14,19,25.9,19.3 c-11.6,9.1-26.4,13.2-41.1,11.5c12.7,8.1,27.4,12.5,42.5,12.5c51,0,78.9-42.2,78.9-78.9c0-1.2,0-2.4-0.1-3.6 C182.7,97.4,189.2,93.7,192.9,88.1z"></path>
|
|
</g>
|
|
</g>
|
|
<circle class="st30" cx="124.4" cy="128.8" r="108.2"></circle>
|
|
</g>
|
|
</svg></a></li>
|
|
<li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank">
|
|
<svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
|
<style type="text/css">
|
|
.st10 {
|
|
fill: #FFFFFF;
|
|
}
|
|
|
|
.st110 {
|
|
fill: none;
|
|
stroke: #FFFFFF;
|
|
stroke-width: 8;
|
|
stroke-miterlimit: 10;
|
|
}
|
|
</style>
|
|
<title>Facebook</title>
|
|
<g>
|
|
<g>
|
|
<path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path>
|
|
</g>
|
|
</g>
|
|
<circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle>
|
|
</svg>
|
|
</a></li>
|
|
<li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
|
<title>Youtube</title>
|
|
<style type="text/css">
|
|
.st4 {
|
|
fill: none;
|
|
stroke: #FFFFFF;
|
|
stroke-width: 8;
|
|
stroke-miterlimit: 10;
|
|
}
|
|
|
|
.st5 {
|
|
fill: #FFFFFF;
|
|
}
|
|
</style>
|
|
<circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle>
|
|
<g transform="translate(0,-952.36218)">
|
|
<path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path>
|
|
</g>
|
|
</svg></a></li>
|
|
</ul>
|
|
</div>
|
|
<div class="col-lg-3 col-12">
|
|
<p class="address_footer text-white">National Library of Medicine<br />
|
|
<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
|
|
Bethesda, MD 20894</a></p>
|
|
</div>
|
|
<div class="col-lg-3 col-12 centered-lg">
|
|
<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
|
|
<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
|
|
<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
|
|
</div>
|
|
<div class="col-lg-3 col-12 centered-lg">
|
|
<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
|
|
<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
|
|
<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-12 centered-lg">
|
|
<nav class="bottom-links">
|
|
<ul class="mt-3">
|
|
<li>
|
|
<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
|
|
</li>
|
|
<li>
|
|
<a class="text-white" href="https://www.nih.gov/">NIH</a>
|
|
</li>
|
|
<li>
|
|
<a class="text-white" href="https://www.hhs.gov/">HHS</a>
|
|
</li>
|
|
<li>
|
|
<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
|
|
</li>
|
|
</ul>
|
|
</nav>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</section>
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentOmnitureBaseJS/InstrumentNCBIConfigJS/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js?v=1"> </script>
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/static/js/hfjs2.js"> </script>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<!--/.page-->
|
|
</div>
|
|
<!--/.wrap-->
|
|
</div><!-- /.twelve_col -->
|
|
</div>
|
|
<!-- /.grid -->
|
|
|
|
<span class="PAFAppResources"></span>
|
|
|
|
<!-- BESelector tab -->
|
|
|
|
|
|
|
|
<noscript><img alt="statistics" src="/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK584020&ncbi_domain=gene&ncbi_report=classic&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK584020/?report=classic&ncbi_pagename=Pediatric Genetic Cholestatic Liver Disease Overview - GeneReviews® - NCBI Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf" /></noscript>
|
|
|
|
|
|
<!-- usually for JS scripts at page bottom -->
|
|
<!--<component id="PageFixtures" label="styles"></component>-->
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal104 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3879255/4121861/3501987/4008961/3893018/3821238/4062932/4209313/4212053/4076480/3921943/3400083/3426610.js" snapshot="books"></script></body>
|
|
</html> |