895 lines
No EOL
158 KiB
XML
895 lines
No EOL
158 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="NBK608431" /><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="/NBK608431/?report=classic" /><meta name="ncbi_pagename" content="Tyrosinemia Type II - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
||
<!-- Logger end -->
|
||
|
||
<title>Tyrosinemia Type II - 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="Tyrosinemia Type II" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2024/10/24" /><meta name="citation_author" content="Zahra Bayzaei" /><meta name="citation_author" content="Seyed Mohsen Dehghani" /><meta name="citation_author" content="Bita Geramizadeh" /><meta name="citation_pmid" content="39446998" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK608431/" /><meta name="citation_keywords" content="Oculocutaneous Tyrosinemia" /><meta name="citation_keywords" content="Richner-Hanhart Syndrome" /><meta name="citation_keywords" content="TAT Deficiency" /><meta name="citation_keywords" content="Tyrosine Aminotransferase Deficiency" /><meta name="citation_keywords" content="Oculocutaneous Tyrosinemia" /><meta name="citation_keywords" content="Richner-Hanhart Syndrome" /><meta name="citation_keywords" content="Tyrosine Aminotransferase Deficiency" /><meta name="citation_keywords" content="TAT Deficiency" /><meta name="citation_keywords" content="Tyrosine aminotransferase" /><meta name="citation_keywords" content="TAT" /><meta name="citation_keywords" content="Tyrosinemia Type II" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Tyrosinemia Type II" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Zahra Bayzaei" /><meta name="DC.Contributor" content="Seyed Mohsen Dehghani" /><meta name="DC.Contributor" content="Bita Geramizadeh" /><meta name="DC.Date" content="2024/10/24" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK608431/" /><meta name="description" content="Tyrosinemia type II is characterized by corneal dystrophy, painful palmoplantar hyperkeratosis, and variable intellectual disability. Individuals diagnosed and treated from early infancy may be asymptomatic or have only mild ocular and skin manifestations. Individuals with delayed diagnosis or lack of treatment present with ocular, skin, and variable cognitive manifestations." /><meta name="og:title" content="Tyrosinemia Type II" /><meta name="og:type" content="book" /><meta name="og:description" content="Tyrosinemia type II is characterized by corneal dystrophy, painful palmoplantar hyperkeratosis, and variable intellectual disability. Individuals diagnosed and treated from early infancy may be asymptomatic or have only mild ocular and skin manifestations. Individuals with delayed diagnosis or lack of treatment present with ocular, skin, and variable cognitive manifestations." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK608431/" /><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/tyrosinemia-2/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK608431/" /><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="CE8DF88A7D7A3A8100000000013E010E.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="medgen">MedGen</option><option value="gene" class="last">Gene</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="#__NBK608431_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK608431_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/tyrosinemia/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/unc80-def/" 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="_NBK608431_"><span class="title" itemprop="name">Tyrosinemia Type II</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Oculocutaneous Tyrosinemia, Richner-Hanhart Syndrome, TAT Deficiency, Tyrosine Aminotransferase Deficiency</div><p class="contrib-group"><span itemprop="author">Zahra Bayzaei</span>, PhD, <span itemprop="author">Seyed Mohsen Dehghani</span>, MD, MPH, and <span itemprop="author">Bita Geramizadeh</span>, MD, APCP.</p><a data-jig="ncbitoggler" href="#__NBK608431_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK608431_ai__"><div class="contrib half_rhythm"><span itemprop="author">Zahra Bayzaei</span>, PhD<div class="affiliation small">Transplant Research Center<br />Shiraz University of Medical Sciences<br />Shiraz, Iran<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@ieazyeb.z" class="oemail">moc.liamg@ieazyeb.z</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Seyed Mohsen Dehghani</span>, MD, MPH<div class="affiliation small">Shiraz University of Medical Sciences<br />Shiraz, Iran<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@msinahghed" class="oemail">moc.liamg@msinahghed</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Bita Geramizadeh</span>, MD, APCP<div class="affiliation small">Shiraz University of Medical Sciences<br />Shiraz, Iran<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@bimareg" class="oemail">moc.liamg@bimareg</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">October 24, 2024</span>.</p><p><em>Estimated reading time: 21 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="tyrosinemia-2.Summary" itemprop="description"><h2 id="_tyrosinemia-2_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Tyrosinemia type II is characterized by corneal dystrophy, painful palmoplantar hyperkeratosis, and variable intellectual disability. Individuals diagnosed and treated from early infancy may be asymptomatic or have only mild ocular and skin manifestations. Individuals with delayed diagnosis or lack of treatment present with ocular, skin, and variable cognitive manifestations.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of tyrosinemia type II is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> by identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>TAT</i> on <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> or – in limited instances – significantly reduced activity of the enzyme tyrosine aminotransferase in liver.</p></div><div><h4 class="inline">Management.</h4><p><i>Targeted therapy:</i> Lifelong restriction of dietary tyrosine and phenylalanine with low-protein diet combined with age-appropriate amino acid (phenylalanine-free and tyrosine-free), vitamin, and mineral supplements.</p><p><i>Supportive care:</i> Lubricating eye drops and ointment; ocular surgery as needed to treat bilateral corneal ulcers; pyridoxine phosphate or a systemic retinoid may be beneficial for skin manifestations; developmental and educational support.</p><p><i>Surveillance:</i> Quantitative analysis of plasma tyrosine and phenylalanine concentrations at each visit; ophthalmology evaluation annually or as needed; evaluation by ophthalmic subspecialist annually or as recommended by ophthalmologist; skin assessment for hyperkeratotic plaques as clinically indicated; monitoring of developmental milestones, neuropsychological testing using age-appropriate standardized assessment batteries, and standardized quality-of-life assessment tools for affected individuals, parents, and/or caregivers annually or at each visit; measurement of plasma calcium, phosphorus, and 25-hydroxyvitamin D concentrations annually or as clinically indicated.</p><p><i>Agents/circumstances to avoid:</i> Increased dietary protein.</p><p><i>Evaluation of relatives at risk</i>: Testing of at-risk sibs of any age is warranted to allow for early diagnosis and treatment.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Tyrosinemia type II is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TAT</i> <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 being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier. Once the <i>TAT</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> for at-risk relatives and prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="tyrosinemia-2.Diagnosis"><h2 id="_tyrosinemia-2_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for tyrosinemia type II have been published.</p><div id="tyrosinemia-2.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Tyrosinemia type II is caused by deficiency of the enzyme tyrosine aminotransferase (TAT) (see <a class="figpopup" href="/books/NBK608431/figure/tyrosinemia-2.F1/?report=objectonly" target="object" rid-figpopup="figtyrosinemia2F1" rid-ob="figobtyrosinemia2F1">Figure 1</a>). Tyrosinemia type II <b>should be suspected</b> in individuals with either <a href="#tyrosinemia-2.Scenario_1_Abnormal_NBS_Re">abnormal newborn screening (NBS) results</a> or <a href="#tyrosinemia-2.Scenario_2_Symptomatic_Ind">clinical and laboratory findings suggestive of tyrosinemia type II</a>. Note: Tyrosinemia type II is not typically included in NBS panels, but may be detected when screening for tyrosinemia type I.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figtyrosinemia2F1" co-legend-rid="figlgndtyrosinemia2F1"><a href="/books/NBK608431/figure/tyrosinemia-2.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figtyrosinemia2F1" rid-ob="figobtyrosinemia2F1"><img class="small-thumb" src="/books/NBK608431/bin/tyrosinemia-2-Image001.gif" src-large="/books/NBK608431/bin/tyrosinemia-2-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndtyrosinemia2F1"><h4 id="tyrosinemia-2.F1"><a href="/books/NBK608431/figure/tyrosinemia-2.F1/?report=objectonly" target="object" rid-ob="figobtyrosinemia2F1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">The tyrosine catabolic pathway FAH = fumarylacetoacetate hydrolase; HGD = homogentisate 1,2-dioxygenase; HPD = 4-hydroxyphenylpyruvic acid dioxygenase; MAI = 4-maleylacetoacetate cis-trans-isomerase; PAH = phenylalanine hydroxylase; TAT = tyrosine aminotransferase <a href="/books/NBK608431/figure/tyrosinemia-2.F1/?report=objectonly" target="object" rid-ob="figobtyrosinemia2F1">(more...)</a></p></div></div><div id="tyrosinemia-2.Scenario_1_Abnormal_NBS_Re"><h4>Scenario 1: Abnormal NBS Result</h4><p>NBS for hepatorenal tyrosinemia (tyrosinemia type I) is typically based on quantification of tyrosine in dried blood spots. Elevated tyrosine above the cutoff reported by the screening laboratory is considered positive and requires follow-up biochemical testing. The identification of an infant with elevated tyrosine without the presence of succinylacetone (which is seen in tyrosinemia type I) should prompt investigation of other defects in tyrosine metabolism, including tyrosinemia type II.</p><p>Additional supportive laboratory findings of tyrosinemia type II include the following:</p><ul><li class="half_rhythm"><div class="half_rhythm">Markedly elevated plasma tyrosine concentration</div><div class="half_rhythm">Note: Elevated plasma tyrosine concentration can be a nonspecific indicator of liver damage or immaturity.</div></li><li class="half_rhythm"><div class="half_rhythm">Normal succinylacetone measured directly from the newborn blood spot by tandem mass spectroscopy</div></li><li class="half_rhythm"><div class="half_rhythm">Absence of succinylacetone in the blood and urine</div></li><li class="half_rhythm"><div class="half_rhythm">Elevated urinary concentration of tyrosine metabolites (e.g., 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate, 4-hydroxyphenylacetate, N-acetyltyrosine, and 4-tyramine)</div></li></ul><p>If the follow-up biochemical testing supports the likelihood of tyrosinemia type II, additional testing is required to confirm the diagnosis (see <a href="#tyrosinemia-2.Establishing_the_Diagnosis">Establishing the Diagnosis</a>).</p><p>Upon identification of high tyrosine levels on NBS (typically >500 µmol/L and may exceed 1,000 µmol/L), consultation with a metabolic physician / biochemical geneticist and specialist metabolic dietitian should be obtained while additional testing is performed to determine whether the result is a true positive NBS and to definitively establish the diagnosis of tyrosinemia type II.</p></div><div id="tyrosinemia-2.Scenario_2_Symptomatic_Ind"><h4>Scenario 2: Symptomatic Individual</h4><p>A symptomatic individual who has either (1) atypical findings associated with later-onset tyrosinemia type II or (2) untreated infantile-onset tyrosinemia type II may present with the following supportive clinical findings, preliminary laboratory findings, and family history.</p><p>
|
||
<b>Clinical findings</b>
|
||
</p><ul><li class="half_rhythm"><div>Ocular manifestations such as increased tearing, photophobia, pain, redness, and bilateral keratitis</div></li><li class="half_rhythm"><div>Skin manifestations such as progressive, painful, nonpruritic, and hyperkeratotic plaques on soles and palms, often associated with hyperhidrosis; usually begin after first year of life</div></li><li class="half_rhythm"><div>Developmental delay, particularly in those with high blood tyrosine concentration</div></li><li class="half_rhythm"><div>Variable intellectual disability</div></li></ul><p>
|
||
<b>Laboratory findings</b>
|
||
</p><ul><li class="half_rhythm"><div>Elevated plasma tyrosine concentration</div></li><li class="half_rhythm"><div>Elevated 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate, and 4-hydroxyphenylacetate and presence of small quantities of N-acetyltyrosine and 4-tyramine on urine organic acid analysis.</div></li><li class="half_rhythm"><div>Serum transaminase levels are usually normal.</div></li></ul><p>Note: Because these laboratory findings are not specific to tyrosinemia type II, additional testing is required to <a href="#tyrosinemia-2.Establishing_the_Diagnosis">establish the diagnosis</a>.</p><p><b>Family history</b> may suggest <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance (e.g., 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 exclude the diagnosis.</p></div></div><div id="tyrosinemia-2.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of tyrosinemia type II <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> by identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>TAT</i> on <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK608431/table/tyrosinemia-2.T.molecular_genetic_testin/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Tmoleculargenetictestin">Table 1</a>) or – in limited instances – significantly reduced activity of the enzyme tyrosine aminotransferase in liver. Because of its relatively high <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a>, <i>TAT</i> molecular genetic testing can obviate the need for enzymatic testing and, thus, is increasingly the preferred confirmatory test for tyrosinemia type II [<a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>].</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#tyrosinemia-2.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>TAT</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>TAT</i> pathogenic variant and one <i>TAT</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p><b>Scenario 1: Abnormal newborn screening (NBS) result.</b> When NBS results and other laboratory findings suggest the diagnosis of tyrosinemia type II, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>TAT</i> is performed first to detect <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>TAT</i> and other genes of interest (see <a href="#tyrosinemia-2.Differential_Diagnosis">Differential Diagnosis</a>) is most 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>. (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></ul><p><b>Scenario 2: A symptomatic individual.</b> When the diagnosis of tyrosinemia type II has not been considered (because an individual has atypical findings associated with later-onset tyrosinemia type II or untreated infantile-onset tyrosinemia type II resulting from NBS not performed or false negative NBS result), <b>comprehensive</b>
|
||
<a href="https://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genomic/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><b>genomic</b></a>
|
||
<b>testing</b> (which 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) is an option. <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. To date, the majority of <i>TAT</i> pathogenic variants reported (e.g., <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>) are within the <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> and are likely to be identified on <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>.</p><p>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>.</p><div id="tyrosinemia-2.T.molecular_genetic_testin" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Tyrosinemia Type II</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.molecular_genetic_testin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.molecular_genetic_testin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tyrosinemia-2.T.molecular_genetic_testin_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_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TAT</i>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>95% <sup>4</sup></td></tr><tr><td headers="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_tyrosinemia-2.T.molecular_genetic_testin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><5% <sup>4, 6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="tyrosinemia-2.TF.1.1"><p class="no_margin">See <a href="/books/NBK608431/#tyrosinemia-2.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="tyrosinemia-2.TF.1.2"><p class="no_margin">See <a href="#tyrosinemia-2.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="tyrosinemia-2.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="tyrosinemia-2.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al [2022]</a> and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bk_pop" href="#tyrosinemia-2.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="tyrosinemia-2.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications. Exome and <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a> may be able to detect deletions/duplications using breakpoint detection or read depth; however, <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> can be lower than gene-targeted deletion/duplication analysis.</p></div></dd><dt>6. </dt><dd><div id="tyrosinemia-2.TF.1.6"><p class="no_margin"><a class="bk_pop" href="#tyrosinemia-2.REF.maydan.2006.620">Maydan et al [2006]</a> and <a class="bk_pop" href="#tyrosinemia-2.REF.legarda.2011.407">Legarda et al [2011]</a> reported large deletions involving <i>TAT</i>.</p></div></dd></dl></div></div></div></div></div><div id="tyrosinemia-2.Clinical_Characteristics"><h2 id="_tyrosinemia-2_Clinical_Characteristics_">Clinical Characteristics</h2><div id="tyrosinemia-2.Clinical_Description"><h3>Clinical Description</h3><p>Tyrosinemia type II is characterized by corneal dystrophy, painful palmoplantar hyperkeratosis, and variable intellectual disability. Individuals diagnosed and treated from early infancy may be asymptomatic or have only mild ocular and skin manifestations. Individuals with delayed diagnosis or lack of treatment present with ocular, skin, and variable cognitive manifestations [<a class="bk_pop" href="#tyrosinemia-2.REF.gliagias.2022.101701">Gliagias et al 2022</a>]. To date, more than 70 individuals have been identified with tyrosinemia type II [<a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="tyrosinemia-2.T.select_features_of_tyros" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of Tyrosinemia Type II</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.select_features_of_tyros/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.select_features_of_tyros_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" style="text-align:left;vertical-align:middle;">Comment</th></tr><tr><th headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2" id="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Diagnosis & treatment in early infancy</th><th headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2" id="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Later diagnosis w/delayed or no treatment</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">75%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~75%-85%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ tearing, photophobia, eye redness, dendritic epithelial ulcers</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Palmoplantar hyperkeratosis, hyperkeratotic plaques</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Intellectual disability</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~60%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_2 hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~10%</td><td headers="hd_h_tyrosinemia-2.T.select_features_of_tyros_1_1_1_3" 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">Based on <a class="bk_pop" href="#tyrosinemia-2.REF.alratrout.2005.422">Al-Ratrout et al [2005]</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.viglizzo.2006.259">Viglizzo et al [2006]</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.legarda.2011.407">Legarda et al [2011]</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.elshabrawi.2013.1">El-Shabrawi & Kamal [2013]</a></p></div></dd></dl></div></div></div><p><b>Ocular manifestations</b> can appear in the first months or first year of life or as late as the fourth decade [<a class="bk_pop" href="#tyrosinemia-2.REF.viglizzo.2006.259">Viglizzo et al 2006</a>]. Ocular symptoms include epiphora (increased tearing), photophobia, pain, and blepharospasm. Ocular signs include corneal clouding, pseudodendritic corneal lesions (usually bilateral), dendritic ulcers, and, rarely, corneal or conjunctival plaques. The dendritic lesions on the cornea stain poorly with fluorescein.</p><ul><li class="half_rhythm"><div>Bacterial, viral, and fungal cultures are typically negative.</div></li><li class="half_rhythm"><div>Ocular manifestations may undergo spontaneous remission and/or recurrence and may occur independently of other clinical manifestations.</div></li><li class="half_rhythm"><div>Individuals are often misdiagnosed with herpes simplex keratitis [<a class="bk_pop" href="#tyrosinemia-2.REF.soares.2017.461">Soares et al 2017</a>].</div></li><li class="half_rhythm"><div>Bilateral corneal lesions unresponsive to antiviral therapies should alert the clinician to the possible diagnosis of tyrosinemia type II, even in the absence of skin lesions [<a class="bk_pop" href="#tyrosinemia-2.REF.macsai.2001.522">Macsai et al 2001</a>].</div></li><li class="half_rhythm"><div>Some individuals with tyrosinemia type II report <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> burning and redness of the eyes since childhood [<a class="bk_pop" href="#tyrosinemia-2.REF.ghalamkarpour.2020.e14072">Ghalamkarpour et al 2020</a>].</div></li><li class="half_rhythm"><div>Asynchronous bilateral eye disease was the sole clinical feature reported in one child age 15 months with negative NBS for tyrosinemia type II [<a class="bk_pop" href="#tyrosinemia-2.REF.gliagias.2022.101701">Gliagias et al 2022</a>]. Following diet modification, tyrosine levels decreased, resulting in significant resolution of ocular symptoms [<a class="bk_pop" href="#tyrosinemia-2.REF.gliagias.2022.101701">Gliagias et al 2022</a>].</div></li><li class="half_rhythm"><div>Dietary treatment (see Management, <a href="#tyrosinemia-2.Targeted_Therapy">Targeted Therapy</a>) has resulted in significant improvement of ocular manifestations in most affected individuals within the first week of treatment [<a class="bk_pop" href="#tyrosinemia-2.REF.elshabrawi.2013.1">El-Shabrawi & Kamal 2013</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.tekin.2015.303">Tekin et al 2015</a>].</div></li><li class="half_rhythm"><div>Corneal lesions recurred in one individual after discontinuation of dietary restrictions [<a class="bk_pop" href="#tyrosinemia-2.REF.macsai.2001.522">Macsai et al 2001</a>].</div></li></ul><p><b>Skin manifestations</b> can appear in the first months of life or be delayed until the second decade [<a class="bk_pop" href="#tyrosinemia-2.REF.rabinowitz.1995.266">Rabinowitz et al 1995</a>]. They typically present as progressive painful hyperkeratotic plaques on the soles and palms, often associated with hyperhidrosis [<a class="bk_pop" href="#tyrosinemia-2.REF.da_silva.2024">da Silva et al 2024</a>]. The fingertips and weightbearing areas of the soles are commonly affected by keratoderma.</p><ul><li class="half_rhythm"><div>One individual had vesicular lesions on the fingertips [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>].</div></li><li class="half_rhythm"><div>Skin manifestations rarely resolve spontaneously and often recur.</div></li><li class="half_rhythm"><div>The pain experienced with palmoplantar keratoderma is a key diagnostic feature, and it can be severe enough to hinder walking [<a class="bk_pop" href="#tyrosinemia-2.REF.viglizzo.2006.259">Viglizzo et al 2006</a>].</div></li><li class="half_rhythm"><div>A skin biopsy from a plantar callus showed hyperkeratosis, hypergranulosis, and acanthosis [<a class="bk_pop" href="#tyrosinemia-2.REF.alratrout.2005.422">Al-Ratrout et al 2005</a>].</div></li><li class="half_rhythm"><div>Dietary restriction of tyrosine and phenylalanine is a highly effective treatment; significant improvement of skin manifestations in most individuals occurs within the first week of treatment [<a class="bk_pop" href="#tyrosinemia-2.REF.tekin.2015.303">Tekin et al 2015</a>].</div></li><li class="half_rhythm"><div>In one individual, the toenails showed subungual hyperkeratosis and secondary nail dystrophy [<a class="bk_pop" href="#tyrosinemia-2.REF.madan.2006.54">Madan & Gupta 2006</a>].</div></li></ul><p><b>Developmental delay</b>. Infants diagnosed and treated in early infancy typically have normal development. Untreated individuals can have global developmental delay including poor feeding with poor appetite and reduced oral intake [<a class="bk_pop" href="#tyrosinemia-2.REF.gliagias.2022.101701">Gliagias et al 2022</a>].</p><p>Mild developmental delay with hemiparesis and seizures has been reported in one individual [<a class="bk_pop" href="#tyrosinemia-2.REF.charfeddine.2006.184">Charfeddine et al 2006</a>].</p><p><b>Intellectual disability.</b> About half of individuals with tyrosinemia type II have mild intellectual disability, but early dietary treatment may reduce this risk [<a class="bk_pop" href="#tyrosinemia-2.REF.legarda.2011.407">Legarda et al 2011</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.nakamura.2015.37">Nakamura et al 2015</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.da_silva.2024">da Silva et al 2024</a>]. Mild language disorder has been reported in three individuals [<a class="bk_pop" href="#tyrosinemia-2.REF.charfeddine.2006.184">Charfeddine et al 2006</a>]. Intellectual disability may be prevented by early dietary restriction of tyrosine and phenylalanine. Language development was reported to improve with dietary treatment [<a class="bk_pop" href="#tyrosinemia-2.REF.tsai.2006.286">Tsai et al 2006</a>].</p><p><b>Nutritional deficiencies</b> can appear in individuals due to limitations of certain amino acids (phenylalanine, tyrosine, and methionine) in the diet. Deficiency of calcium, phosphorus, and 25-hydroxyvitamin D have been observed.</p><p>
|
||
<b>Other</b>
|
||
</p><ul><li class="half_rhythm"><div>Isolated geographic tongue with otherwise normal clinical findings (1 individual) [<a class="bk_pop" href="#tyrosinemia-2.REF.bouyacoub.2013.45">Bouyacoub et al 2013</a>]</div></li><li class="half_rhythm"><div>Self-harm (agitation with paroxysms of head banging and hand and tongue biting) and diffuse plantar keratoderma (1 individual) [<a class="bk_pop" href="#tyrosinemia-2.REF.madan.2006.54">Madan & Gupta 2006</a>]</div></li></ul></div><div id="tyrosinemia-2.GenotypePhenotype_Correlat"><h3>Genotype-Phenotype Correlations</h3><p>Precise <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> are difficult to determine, as most <i>TAT</i> pathogenic variants reported to date are not recurrent [<a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>].</p><p>The most common variant reported to date, <a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Arg57Ter</a>, has been reported in ten affected individuals from three families [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>]. Individuals <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> for this <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> typically present in the neonatal period and have eye and skin manifestations.</p></div><div id="tyrosinemia-2.Nomenclature"><h3>Nomenclature</h3><p>Tyrosinemia type II was previously referred to as keratosis palmoplantaris with corneal dystrophy.</p></div><div id="tyrosinemia-2.Prevalence"><h3>Prevalence</h3><p>Tyrosinemia type II is rare, with an incidence of less than one in 250,000 [<a class="bk_pop" href="#tyrosinemia-2.REF.bouyacoub.2013.45">Bouyacoub et al 2013</a>]. Fewer than 100 affected individuals from various ethnic backgrounds have been reported to date [<a class="bk_pop" href="#tyrosinemia-2.REF.janakiraman.2006.161">Janakiraman et al 2006</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.elshabrawi.2013.1">El-Shabrawi & Kamal 2013</a>].</p><p>Founder pathogenic variants have been reported in populations from northern Italy (Lombardy and Tuscany; <a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Arg57Ter</a>), Tunisia (<a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Cys151Tyr</a>), Lebanon (<a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Arg297Ter</a>), Palestine (<a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Arg417Ter</a>), and Gran Canaria (<a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">p.Pro406Leu</a>), which has a population of Mediterranean ancestry primarily from continental Spain and northern Africa [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>]. Consanguinity is frequently reported in parents of affected individuals, which may contribute to the higher prevalence of this disorder among Arab populations [<a class="bk_pop" href="#tyrosinemia-2.REF.charfeddine.2006.184">Charfeddine et al 2006</a>].</p></div></div><div id="tyrosinemia-2.Genetically_Related_Alleli"><h2 id="_tyrosinemia-2_Genetically_Related_Alleli_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>TAT</i>.</p></div><div id="tyrosinemia-2.Differential_Diagnosis"><h2 id="_tyrosinemia-2_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Hypertyrosinemia.</b> Other causes of hypertyrosinemia include genetic tyrosine metabolism disorders (see <a href="/books/NBK608431/table/tyrosinemia-2.T.genes_of_interest_in_the/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Tgenesofinterestinthe">Table 3</a>) and acquired conditions such as the following:</p><ul><li class="half_rhythm"><div>Transient tyrosinemia of the newborn</div></li><li class="half_rhythm"><div>Immature liver</div></li><li class="half_rhythm"><div>Hypertyrosinemia due to liver disease</div></li></ul><p><b>Corneal lesions.</b> Because ocular features are often the initial manifestations of tyrosinemia type II, pseudodendritic keratitis is often mistaken for herpes simplex keratitis.</p><p>Genetic disorders of interest in the differential diagnosis of tyrosinemia type II are listed in <a href="/books/NBK608431/table/tyrosinemia-2.T.genes_of_interest_in_the/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Tgenesofinterestinthe">Table 3</a>.</p><div id="tyrosinemia-2.T.genes_of_interest_in_the" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Tyrosinemia Type II</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.genes_of_interest_in_the/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.genes_of_interest_in_the_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Disorder</th></tr><tr><th headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4" id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/tyrosinemia type II</th><th headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4" id="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from tyrosinemia type II</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FAH</i>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/tyrosinemia/">Tyrosinemia type I</a>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertyrosinemia</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Liver & kidney dysfunction</div></li><li class="half_rhythm"><div>↑ succinylacetone concentration in blood & urine</div></li><li class="half_rhythm"><div>Hypoglycemia</div></li><li class="half_rhythm"><div>High alkaline phosphatase</div></li><li class="half_rhythm"><div>Moderately ↑ plasma concentration of tyrosine, phenylalanine, & other amino acids, esp methionine (due to secondary inhibition of methionine adenosyltransferase)</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>HPD</i>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tyrosinemia type III (OMIM <a href="https://omim.org/entry/276710" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">276710</a>)</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertyrosinemia</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Moderately ↑ plasma concentration of tyrosine</div></li><li class="half_rhythm"><div>Low activity of enzyme HPD in liver biopsy</div></li><li class="half_rhythm"><div>Ataxia & seizures</div></li><li class="half_rhythm"><div>Absence of skin & ocular lesions</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MBTPS2</i>
|
||
<br />
|
||
<i>PERP</i>
|
||
<br />
|
||
<i>TRPV3</i>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Olmsted syndrome (OMIM <a href="https://omim.org/phenotypicSeries/PS614594" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS614594</a>)</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />XL</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Palmoplantar keratoderma w/periorificial keratotic plaques</td><td headers="hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_1_4 hd_h_tyrosinemia-2.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Sparse hair & onychodystrophy</div></li><li class="half_rhythm"><div>Joint abnormalities</div></li><li class="half_rhythm"><div>Hypotrichosis</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; HPD = 4-hydroxyphenylpyruvic acid dioxygenase; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd></dl></div></div></div></div><div id="tyrosinemia-2.Management"><h2 id="_tyrosinemia-2_Management_">Management</h2><p>No clinical practice guidelines for tyrosinemia type II have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.</p><p>When tyrosinemia type II is suspected during the diagnostic evaluation due to high levels of tyrosine (typically >500 µmol/L and may exceed 1,000 µmol/L), metabolic treatment should be initiated immediately (see <a href="#tyrosinemia-2.Targeted_Therapy">Targeted Therapy</a>).</p><p>Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach including multiple subspecialists, with oversight and expertise from a specialized metabolic center and the involvement of a dietitian with specialized training.</p><div id="tyrosinemia-2.Evaluations_Following_Init"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with tyrosinemia type II, the evaluations summarized <a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_reco/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttyrosinemiatypeiireco">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="tyrosinemia-2.T.tyrosinemia_type_ii_reco" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Tyrosinemia Type II: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_reco/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.tyrosinemia_type_ii_reco_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for epiphora, photophobia, & blepharospasm & more complex findings (e.g., corneal clouding, corneal lesions, & dendritic ulcers) that may require referral for subspecialty care &/or low vision services</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin exam</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for hyperkeratotic plaques on soles, palms (esp thenar & hypothenar areas), & fingertips</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech-language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Metabolic</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/metabolic physician / biochemical geneticist & specialist metabolic dietitian</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To initiate dietary restriction of tyrosine & phenylalanine</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a <a class="def" href="/books/n/gene/glossary/def-item/pedigree/">pedigree</a> & inform affected persons & their families re nature, MOI, & implications of tyrosinemia type II to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By clinicians, wider care team, & family support organizations</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#tyrosinemia-2.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a></div></li><li class="half_rhythm"><div>Social work involvement for parental support</div></li><li class="half_rhythm"><div>Home nursing referral</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="tyrosinemia-2.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="tyrosinemia-2.Treatment_of_Manifestation"><h3>Treatment of Manifestations</h3><div id="tyrosinemia-2.Targeted_Therapy"><h4>Targeted Therapy</h4><p>
|
||
<i>In GeneReviews, a targeted therapy is one that addresses the specific underlying mechanism of disease causation (regardless of whether the therapy is significantly efficacious for one or more manifestation of the genetic condition); would otherwise not be considered without knowledge of the underlying genetic cause of the condition; or could lead to a cure</i>. —ED</p><p><b>Restriction of dietary tyrosine and phenylalanine.</b> Targeted therapy for tyrosinemia type II aims to reduce plasma tyrosine concentration and consists of a low-protein diet with age-appropriate amino acid (tyrosine- and phenylalanine-free), vitamin, and mineral supplements.</p><ul><li class="half_rhythm"><div>Treatment is a lifelong tyrosine- and phenylalanine-restricted diet. Initially this is in the form of a prescribed infant formula. After weaning, a low-protein diet is prescribed and age-appropriate amino acid (tyrosine- and phenylalanine-free), vitamin, and mineral supplements are given.</div></li><li class="half_rhythm"><div>A diet that is low in tyrosine and phenylalanine can help correct chemical abnormalities and lead to significant improvement in skin and eye lesions.</div></li><li class="half_rhythm"><div>Early dietary restriction of tyrosine can help prevent intellectual disability [<a class="bk_pop" href="#tyrosinemia-2.REF.elshabrawi.2013.1">El-Shabrawi & Kamal 2013</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.murphy.2016">Murphy 2016</a>].</div></li></ul></div><div id="tyrosinemia-2.Supportive_Care"><h4>Supportive Care</h4><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_trea/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttyrosinemiatypeiitrea">Table 5</a>).</p><div id="tyrosinemia-2.T.tyrosinemia_type_ii_trea" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Tyrosinemia Type II: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_trea/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.tyrosinemia_type_ii_trea_lrgtbl__"><table><thead><tr><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Principle/Manifestation</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lubricating eye drops & ointment</div></li><li class="half_rhythm"><div>Ocular surgery to treat bilateral corneal ulcers</div></li></ul>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ocular manifestations improve & may resolve w/dietary restriction of tyrosine & phenylalanine (see <a href="#tyrosinemia-2.Targeted_Therapy">Targeted Therapy</a>).</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pyridoxine phosphate or systemic retinoid may be beneficial.</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin manifestations often resolve w/dietary restriction of tyrosine & phenylalanine (see <a href="#tyrosinemia-2.Targeted_Therapy">Targeted Therapy</a>).</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay /</b>
|
||
<br />
|
||
<b>Intellectual disability</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental & educational support as needed</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_trea_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></div></div><div id="tyrosinemia-2.Surveillance"><h3>Surveillance</h3><p>In addition to regular evaluations by a metabolic specialist and metabolic dietician, the evaluations summarized in <a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_reco_1/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttyrosinemiatypeiireco1">Table 6</a> are recommended to monitor existing manifestations, the individual's response to targeted therapy and supportive care, and the emergence of new manifestations.</p><div id="tyrosinemia-2.T.tyrosinemia_type_ii_reco_1" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Tyrosinemia Type II: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.tyrosinemia_type_ii_reco_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_lrgtbl__"><table><thead><tr><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency/Comment</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Metabolic/</b>
|
||
<br />
|
||
<b>Nutrition</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Quantitative analysis of plasma tyrosine & phenylalanine concentrations</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval by ophthalmologist to assess for epiphora, photophobia, blepharospasm, & keratitis</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as needed</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Eval by ophthalmic subspecialist to assess for more complex findings (e.g., corneal clouding, pseudodendritic corneal lesions, dendritic ulcers, & corneal or conjunctival plaques)</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as recommended by ophthalmologist</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin manifestations</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin assessment for hyperkeratotic plaques</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Delayed acquisition of developmental milestones</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitoring of developmental milestones</div></li><li class="half_rhythm"><div>Neuropsychological testing using age-appropriate standardized assessment batteries</div></li><li class="half_rhythm"><div>Standardized quality-of-life assessment tools for affected persons & parents/caregivers</div></li></ul>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or at each visit</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Nutritional deficiencies</b>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of plasma calcium, phosphorus, & 25-hydroxyvitamin D concentrations</td><td headers="hd_h_tyrosinemia-2.T.tyrosinemia_type_ii_reco_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as clinically indicated</td></tr></tbody></table></div></div></div><div id="tyrosinemia-2.AgentsCircumstances_to_Avo"><h3>Agents/Circumstances to Avoid</h3><p>Avoid increased dietary protein.</p></div><div id="tyrosinemia-2.Evaluation_of_Relatives_at"><h3>Evaluation of Relatives at Risk</h3><p>Testing of at-risk sibs of any age is warranted to allow for early diagnosis and treatment of tyrosinemia type II.</p><p><b>Prenatal testing of a fetus at risk.</b> When the pathogenic variants causing tyrosinemia type II in the family are known, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> of fetuses at risk may be performed via amniocentesis or chorionic villus sampling to facilitate institution of treatment at birth.</p><p><b>Newborn sib.</b> If <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> was not performed – in parallel with newborn screening – testing for the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> <i>TAT</i> pathogenic variants or measurement of plasma tyrosine concentration and excretion of 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate, and 4-hydroxyphenylacetate on urine organic acid analysis can be performed.</p><p>See <a href="#tyrosinemia-2.Related_Genetic_Counseling">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="tyrosinemia-2.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Infants born to women with untreated tyrosinemia type II may have an increased risk of intrauterine growth deficiency and developmental delay [<a class="bk_pop" href="#tyrosinemia-2.REF.cerone.2002.317">Cerone et al 2002</a>]. Careful dietary control of plasma tyrosine concentration during pregnancy is recommended.</p></div><div id="tyrosinemia-2.Therapies_Under_Investigat"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="tyrosinemia-2.Genetic_Counseling"><h2 id="_tyrosinemia-2_Genetic_Counseling_">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="tyrosinemia-2.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Tyrosinemia type II is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="tyrosinemia-2.Risk_to_Family_Members"><h3>Risk to Family Members</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 a <i>TAT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>If a molecular diagnosis has been 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 the proband to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TAT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and 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, it is possible that one of the pathogenic variants identified in the proband 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="#tyrosinemia-2.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> that was not detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> and that resulted in the artifactual appearance of homozygosity;</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> that 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>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</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 <i>TAT</i> <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 being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Unless an affected individual's reproductive partner also has tyrosinemia type II or is a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, offspring will be obligate heterozygotes (carriers) for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>TAT</i>.</p><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 <i>TAT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="tyrosinemia-2.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>TAT</i> pathogenic variants in the family.</p></div><div id="tyrosinemia-2.Related_Genetic_Counseling"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#tyrosinemia-2.Evaluation_of_Relatives_at">Evaluation of Relatives at Risk</a> for information on evaluating at-risk sibs for the purpose of early diagnosis and treatment.</p><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 reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing should be considered for the reproductive partners of individuals affected with tyrosinemia type II and individuals known to be carriers of a <i>TAT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, particularly if <a class="def" href="/books/n/gene/glossary/def-item/consanguinity/">consanguinity</a> is likely and/or both partners are of the same ancestry (see <a href="#tyrosinemia-2.Prevalence">Prevalence</a>). <i>TAT</i> founder variants have been identified in several populations (see <a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobtyrosinemia2Ttatpathogenicvariants">Table 7</a>).</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#tyrosinemia-2.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="tyrosinemia-2.Prenatal_Testing_and_Preim"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>TAT</i> 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="tyrosinemia-2.Resources"><h2 id="_tyrosinemia-2_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>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/tyrosinemia/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Tyrosinemia</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Metabolic Support UK</b>
|
||
</div><div>United Kingdom</div><div><b>Phone:</b> 0845 241 2173</div><div>
|
||
<a href="https://metabolicsupportuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">metabolicsupportuk.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Newborn Screening in Your State</b>
|
||
</div><div>Health Resources & Services Administration</div><div>
|
||
<a href="https://newbornscreening.hrsa.gov/your-state" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">newbornscreening.hrsa.gov/your-state</a>
|
||
</div></li></ul>
|
||
</div><div id="tyrosinemia-2.Molecular_Genetics"><h2 id="_tyrosinemia-2_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="tyrosinemia-2.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Tyrosinemia Type II: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_tyrosinemia-2.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/6898" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>TAT</i>
|
||
</a>
|
||
</td><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=6898" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">16q22<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P17735" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Tyrosine aminotransferase</a>
|
||
</td><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/TAT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TAT database</a>
|
||
</td><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=TAT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TAT</a>
|
||
</td><td headers="hd_b_tyrosinemia-2.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TAT[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TAT</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="tyrosinemia-2.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="tyrosinemia-2.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Tyrosinemia Type II (<a href="/omim/276600,613018" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/276600" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">276600</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TYROSINEMIA, TYPE II; TYRSN2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/613018" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613018</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TYROSINE AMINOTRANSFERASE; TAT</td></tr></tbody></table></div></div><div id="tyrosinemia-2.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>TAT</i> encodes the enzyme tyrosine aminotransferase (TAT), the first in a series of five enzymes that catalyze reversible transamination of tyrosine to 4-hydroxyphenylpyruvate. Reduced TAT function results in the accumulation of upstream byproducts of tyrosine and phenylalanine.</p><p>TAT is a homodimer and is composed of two identical polypeptide chains. It is expressed in the liver, kidneys, and brain. The enzyme has the highest activity in the liver. In TAT, the first 38 amino acids may not be involved in enzyme dimerization and are not required in the active site stability and enzyme-substrate interactions. This N-terminal fragment, however, is required for targeting by the ubiquitin-proteasome pathway, which degrades proteins to small peptides.</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div id="tyrosinemia-2.T.tat_pathogenic_variants" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>TAT</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK608431/table/tyrosinemia-2.T.tat_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tyrosinemia-2.T.tat_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000353.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000353<wbr style="display:inline-block"></wbr>.3</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000344.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000344<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.169C>T</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg57Ter</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Founder variant identified in northern Italy (Lombardy & Tuscany)</div></li><li class="half_rhythm"><div>Most common variant reported to date (10 affected persons from 3 families) [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>, <a class="bk_pop" href="#tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei et al 2022</a>]</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.452G>A</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys151Tyr</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant identified in Tunisian population [<a class="bk_pop" href="#tyrosinemia-2.REF.charfeddine.2006.184">Charfeddine et al 2006</a>]</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.889C>T</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg297Ter</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant identified in Lebanese population [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>]</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1217C>T</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro406Leu</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant identified in Gran Canaria population [<a class="bk_pop" href="#tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana et al 2017</a>]</td></tr><tr><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1249C>T</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg417Ter</td><td headers="hd_h_tyrosinemia-2.T.tat_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant identified in Palestinian population [<a class="bk_pop" href="#tyrosinemia-2.REF.maydan.2006.620">Maydan et al 2006</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="tyrosinemia-2.Chapter_Notes"><h2 id="_tyrosinemia-2_Chapter_Notes_">Chapter Notes</h2><div id="tyrosinemia-2.Author_Notes"><h3>Author Notes</h3><p>Dr Bita Geramizadeh is a molecular pathologist. Her clinical and research interests include transplant hepatology, acute liver failure, and inherited metabolic disorders of the liver. She is the author of numerous (more than 450) original manuscripts and reviews on the subject. Her research has been in both the clinical and basic science spheres. Dr Geramizadeh has launched and established a transplant research center and national registry trial for inherited metabolic disorders with a data coordinating center at the Shiraz University of Medical Sciences. She is the vice president of the Association for Inherited Metabolic Disorders (Ibn Sina).</p><p>Dr Seyed Mohsen Dehghani is a professor of pediatric gastroenterology and hepatology with experience in inherited disorders and more than 200 highly cited published papers.</p><p>Dr Zahra Beyzaei is a molecular and biochemical geneticist. She is a staff scientist in the transplant research center at the Shiraz University of Medical Sciences. She would be happy to communicate with persons who have any questions regarding tyrosinemia type II disease. Contact Dr Beyzaei to inquire about review of <i>TAT</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>.</p></div><div id="tyrosinemia-2.Acknowledgments"><h3>Acknowledgments</h3><p>We extend our gratitude to the individuals with tyrosinemia type II and their families, our institutions, laboratory personnel, and researchers, as well as the Association for Inherited Metabolic Disorders (Ibn Sina), for their dedicated efforts and collaborative work.</p></div><div id="tyrosinemia-2.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>24 October 2024 (sw) Review posted live</div></li><li class="half_rhythm"><div>17 June 2024 (bg) Original submission</div></li></ul></div></div><div id="tyrosinemia-2.References"><h2 id="_tyrosinemia-2_References_">References</h2><div id="tyrosinemia-2.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.alratrout.2005.422">Al-Ratrout
|
||
JT, Al-Muzian
|
||
M, Al-Nazer
|
||
M, Ansari
|
||
NA. Plantar keratoderma: a manifestation of tyrosinemia type II (Richner-Hanhart syndrome).
|
||
Ann Saudi Med.
|
||
2005;25:422-4.
|
||
[<a href="/pmc/articles/PMC6089717/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6089717</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16270769" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16270769</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.beyzaei.2022.424">Beyzaei
|
||
Z, Nabavizadeh
|
||
S, Karimzadeh
|
||
S, Geramizadeh
|
||
B. The mutation spectrum and ethnic distribution of non-hepatorenal tyrosinemia (types II, III).
|
||
Orphanet J Rare Dis.
|
||
2022;17:424.
|
||
[<a href="/pmc/articles/PMC9724276/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9724276</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36471409" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36471409</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.bouyacoub.2013.45">Bouyacoub
|
||
Y, Zribi
|
||
H, Azzouz
|
||
H, Nasrallah
|
||
F, Abdelaziz
|
||
RB, Kacem
|
||
M, Rekaya
|
||
B, Messaoud
|
||
O, Romdhane
|
||
L, Charfeddine
|
||
C, Bouziri
|
||
M, Bouziri
|
||
S, Tebib
|
||
N, Mokni
|
||
M, Kaabachi
|
||
N, Boubaker
|
||
S, Abdelhak
|
||
S. Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome.
|
||
Gene.
|
||
2013;529:45-9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/23954227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23954227</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.cerone.2002.317">Cerone
|
||
R, Fantasia
|
||
AR, Castellano
|
||
E, Moresco
|
||
L, Schiaffino
|
||
MC, R. G. Pregnancy and tyrosinaemia type II.
|
||
J Inherit Metab Dis.
|
||
2002;25:317-18.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/12227462" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12227462</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.charfeddine.2006.184">Charfeddine
|
||
C, Monastiri
|
||
K, Mokni
|
||
M, Laadjimi
|
||
A, Kaabachi
|
||
N, Perin
|
||
O, Nilges
|
||
M, Kassar
|
||
S, Keirallah
|
||
M, Guediche
|
||
MN, Kamoun
|
||
MR, Tebib
|
||
N, Ben Dridi
|
||
MF, Boubaker
|
||
S, Ben Osman
|
||
A, Abdelhak
|
||
S. Clinical and mutational investigations of tyrosinemia type II in northern Tunisia: identification and structural characterization of two novel TAT mutations.
|
||
Mol Genet Metab.
|
||
2006;88:184-91.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16574453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16574453</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.da_silva.2024">da Silva
|
||
ISF, Sopa
|
||
I, Gomes
|
||
D, Peixoto
|
||
L, Oliveira
|
||
A. From skin lesions to tyrosinemia type II diagnosis.
|
||
J Inherit Metab Dis.
|
||
2024. Epub ahead of print.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/38408363" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38408363</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.elshabrawi.2013.1">El-Shabrawi
|
||
M, Kamal
|
||
NM. Current management options for tyrosinemia. Orphan Drugs: Research and Reviews.
|
||
2013;3:1-9.</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.ghalamkarpour.2020.e14072">Ghalamkarpour
|
||
F, Niknezhad
|
||
N, Niknejad
|
||
N.
|
||
Familial Richner-Hanhart syndrome: report of a sibling with incomplete presentation.
|
||
Dermatol Ther.
|
||
2020;33:e14072.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/32713067" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32713067</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.gliagias.2022.101701">Gliagias
|
||
V, Denisova
|
||
K, Kang
|
||
JJ. A child with dendritiform eye lesions and developmental delay.
|
||
Am J Ophthalmol Case Rep.
|
||
2022;28:101701.
|
||
[<a href="/pmc/articles/PMC9471959/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9471959</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36118278" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36118278</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.huang.2022.389">Huang
|
||
SJ, Amendola
|
||
LM, Sternen
|
||
DL. Variation among DNA banking consent forms: points for clinicians to bank on.
|
||
J Community Genet.
|
||
2022;13:389-97.
|
||
[<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.janakiraman.2006.161">Janakiraman
|
||
L, Sathiyasekaran
|
||
M, Deenadayalan
|
||
M, Ganesh
|
||
R, Mahesh
|
||
U.
|
||
Richner Hanhart syndrome.
|
||
Indian J Pediatr.
|
||
2006;73:161-2.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16514229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16514229</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.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="tyrosinemia-2.REF.legarda.2011.407">Legarda
|
||
M, Wlodarczyk
|
||
K, Lage
|
||
S, Andrade
|
||
F, Kim
|
||
GJ, Bausch
|
||
E, Scherer
|
||
G, LJ. A-E. A large TAT deletion in a tyrosinaemia type II patient.
|
||
Mol Genet Metab.
|
||
2011;104:407-9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/21636300" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21636300</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.macsai.2001.522">Macsai
|
||
MS, Schwartz
|
||
TL, Hinkle
|
||
D, Hummel
|
||
MB, Mulhern
|
||
MG, Rootman
|
||
D. Tyrosinemia type II: nine cases of ocular signs and symptoms.
|
||
Am J Ophthalmol.
|
||
2001;132:522-7.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/11589874" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11589874</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.madan.2006.54">Madan
|
||
V, Gupta
|
||
U.
|
||
Tyrosinaemia type II with diffuse plantar keratoderma and self-mutilation.
|
||
Clin Exp Dermatol.
|
||
2006;31:54-6.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16309482" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16309482</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.maydan.2006.620">Maydan
|
||
G, Andresen
|
||
BS, Madsen
|
||
PP, Zeigler
|
||
M, Raas-Rothschild
|
||
A, Zlotogorski
|
||
A, Gutman
|
||
A, Korman
|
||
SH. TAT gene mutation analysis in three Palestinian kindreds with oculocutaneous tyrosinaemia type II; characterization of a silent exonic transversion that causes complete missplicing by exon 11 skipping.
|
||
J Inherit Metab Dis.
|
||
2006;29:620-6.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16917729" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16917729</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.murphy.2016">Murphy E. Tyrosinaemia type I. In: CEM Hollak, R Lachmann, eds. <em>Inherited Metabolic Disease in Adults: A Clinical Guide.</em> New York: Oxford Academic;2016:chap. 14.</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.nakamura.2015.37">Nakamura
|
||
K, Matsumoto
|
||
S, Mitsubuchi
|
||
H, Endo
|
||
F. Diagnosis and treatment of hereditary tyrosinemia in Japan.
|
||
Pediatr Int.
|
||
2015;57:37-40.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/25443793" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25443793</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.pe_aquintana.2017.306">Peña-Quintana
|
||
L, Scherer
|
||
G, Curbelo-Estévez
|
||
ML, Jiménez-Acosta
|
||
F, Hartmann
|
||
B, La Roche
|
||
F, Meavilla-Olivas
|
||
S, Pérez-Cerdá
|
||
C, García-Segarra
|
||
N, Giguère
|
||
Y, Huppke
|
||
P, Mitchell
|
||
GA, Mönch
|
||
E, Trump
|
||
D, Vianey-Saban
|
||
C, Trimble
|
||
ER, Vitoria-Miñana
|
||
I, Reyes-Suárez
|
||
D, Ramírez-Lorenzo
|
||
T, Tugores
|
||
A. Tyrosinemia type II: mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation.
|
||
Clin Genet.
|
||
2017;92:306-17.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28255985" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28255985</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.rabinowitz.1995.266">Rabinowitz
|
||
LG, Williams
|
||
LR, Anderson
|
||
CE, Mazur
|
||
A, Kaplan
|
||
P. Painful keratoderma and photophobia: hallmarks of tyrosinemia type II.
|
||
J Pediatr.
|
||
1995;126:266-9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/7844676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7844676</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.richards.2015.405">Richards
|
||
S, Aziz
|
||
N, Bale
|
||
S, Bick
|
||
D, Das
|
||
S, Gastier-Foster
|
||
J, Grody
|
||
WW, Hegde
|
||
M, Lyon
|
||
E, Spector
|
||
E, Voelkerding
|
||
K, Rehm
|
||
HL, et al.
|
||
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
||
Genet Med.
|
||
2015;17:405-24.
|
||
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.soares.2017.461">Soares
|
||
DC, Stroparo
|
||
MN, Lian
|
||
YC, Takakura
|
||
CY, Wolf
|
||
S, Betz
|
||
R, Kim
|
||
CA. Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome.
|
||
J Inherit Metab Dis.
|
||
2017;40:461-2.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27832414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27832414</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.stenson.2020.1197">Stenson
|
||
PD, Mort
|
||
M, Ball
|
||
EV, Chapman
|
||
M, Evans
|
||
K, Azevedo
|
||
L, Hayden
|
||
M, Heywood
|
||
S, Millar
|
||
DS, Phillips
|
||
AD, Cooper
|
||
DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting.
|
||
Hum Genet.
|
||
2020;139:1197-207.
|
||
[<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.tekin.2015.303">Tekin
|
||
B, Yucelten
|
||
D, Zeybek
|
||
CA, Kiykim
|
||
E, Wehner
|
||
M, Betz
|
||
RC, Toker
|
||
AE. Oculocutaneous tyrosinemia: a case report with delayed diagnosis and excellent response to dietary modification.
|
||
Indian J Dermatol Venereol Leprol.
|
||
2015;81:303-5.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/25784227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25784227</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.tsai.2006.286">Tsai
|
||
CP, Lin
|
||
PY, Lee
|
||
NC, Niu
|
||
DM, Lee
|
||
SM, Hsu
|
||
WM. Corneal lesion as the initial manifestation of tyrosinemia type II.
|
||
J Chin Med Assoc.
|
||
2006;69:286-8.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16863017" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16863017</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tyrosinemia-2.REF.viglizzo.2006.259">Viglizzo
|
||
GM, Occella
|
||
C, Bleidl
|
||
D, Rongioletti
|
||
F. Richner-Hanhart syndrome (tyrosinemia II): early diagnosis of an incomplete presentation with unusual findings.
|
||
Pediatr Dermatol.
|
||
2006;23:259-61.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/16780475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16780475</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: NBK608431</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/39446998" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">39446998</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/tyrosinemia/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/unc80-def/" 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=NBK608431&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/NBK608431/?report=reader">PubReader</a></li><li><a href="/books/NBK608431/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK608431" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK608431" style="display:none" title="Cite this Page"><div class="bk_tt">Bayzaei Z, Dehghani SM, Geramizadeh B. Tyrosinemia Type II. 2024 Oct 24. 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/NBK608431/pdf/Bookshelf_NBK608431.pdf">PDF version of this page</a> (517K)</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="#tyrosinemia-2.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#tyrosinemia-2.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#tyrosinemia-2.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#tyrosinemia-2.Genetically_Related_Alleli" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#tyrosinemia-2.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#tyrosinemia-2.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#tyrosinemia-2.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#tyrosinemia-2.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#tyrosinemia-2.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#tyrosinemia-2.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#tyrosinemia-2.References" ref="log$=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>Key Sections in This GeneReview</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="#tyrosinemia-2.Targeted_Therapy">Targeted Therapy</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=6898[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">TAT</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=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=5687886" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=5687886" ref="log$=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=5687886" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=5687886" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</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/35862567" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Carnitine-Acylcarnitine Translocase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Carnitine-Acylcarnitine Translocase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Morales Corado JA, Lee CU, Enns GM. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301656" ref="ordinalpos=1&linkpos=2&log$=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> Adenosine Deaminase 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> Adenosine Deaminase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Hershfield M, Tarrant T. </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/20301631" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Citrullinemia Type I.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Citrullinemia Type I.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Quinonez SC, Lee KN. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301570" ref="ordinalpos=1&linkpos=4&log$=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> Alpha-Mannosidosis.</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> Alpha-Mannosidosis.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Ficicioglu C, Stepien KM. </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/25032271" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Dihydrolipoamide Dehydrogenase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Dihydrolipoamide Dehydrogenase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Quinonez SC, Thoene JG. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=39446998" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=39446998" 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=67d7b40c2f30673f7b5082f4">Tyrosinemia Type II - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Tyrosinemia Type II - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d7b40b67c23b31e0028730">Table B. [OMIM Entries for Tyrosinemia Type II (View All in OMIM)]. - GeneReview...</a><div class="ralinkpop offscreen_noflow">Table B. [OMIM Entries for Tyrosinemia Type II (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d7b3f1cde49f3df7376ec5">RecName: Full=Tyrosine aminotransferase; Short=TAT; AltName: Full=L-tyrosine:2-o...</a><div class="ralinkpop offscreen_noflow">RecName: Full=Tyrosine aminotransferase; Short=TAT; AltName: Full=L-tyrosine:2-oxoglutarate aminotransferase<div class="brieflinkpopdesc">gi|114713|sp|P17735.1|ATTY_HUMAN</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d7b3f0cde49f3df7376b7d">Homo sapiens chromosome 16 clone RP11-510M2, complete sequence</a><div class="ralinkpop offscreen_noflow">Homo sapiens chromosome 16 clone RP11-510M2, complete sequence<div class="brieflinkpopdesc">gi|15808510|gnl|lanlchgs|510M2|gb|A 47.9|</div></div><div class="tertiary">Nucleotide</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d7b3e62f30673f7b4fb628">Tyrosinemia type II</a><div class="ralinkpop offscreen_noflow">Tyrosinemia type II<div class="brieflinkpopdesc"></div></div><div class="tertiary">MedGen</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">
|
||
|
||
<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=NBK608431&ncbi_domain=gene&ncbi_report=classic&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK608431/?report=classic&ncbi_pagename=Tyrosinemia Type II - 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 portal106 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> |