305 lines
164 KiB
Text
305 lines
164 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK488189">
|
|
<meta name="ncbi_domain" content="gene">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK488189/?report=reader">
|
|
<meta name="ncbi_pagename" content="ASAH1-Related Disorders - GeneReviews® - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>ASAH1-Related Disorders - GeneReviews® - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/gene/arsacs/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/aspm-pm/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="ASAH1-Related Disorders">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2018/03/29">
|
|
<meta name="citation_author" content="David A Dyment">
|
|
<meta name="citation_author" content="Steffany AL Bennett">
|
|
<meta name="citation_author" content="Jeffrey A Medin">
|
|
<meta name="citation_author" content="Thierry Levade">
|
|
<meta name="citation_pmid" content="29595935">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK488189/">
|
|
<meta name="citation_keywords" content="Farber Disease">
|
|
<meta name="citation_keywords" content="Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME)">
|
|
<meta name="citation_keywords" content="Spinal Muscular Atrophy without Epilepsy">
|
|
<meta name="citation_keywords" content="Progressive Adult-Onset Brachydactyly Due to Osteolysis">
|
|
<meta name="citation_keywords" content="Acid ceramidase">
|
|
<meta name="citation_keywords" content="ASAH1">
|
|
<meta name="citation_keywords" content="ASAH1-Related Disorders">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="ASAH1-Related Disorders">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="David A Dyment">
|
|
<meta name="DC.Contributor" content="Steffany AL Bennett">
|
|
<meta name="DC.Contributor" content="Jeffrey A Medin">
|
|
<meta name="DC.Contributor" content="Thierry Levade">
|
|
<meta name="DC.Date" content="2018/03/29">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK488189/">
|
|
<meta name="description" content="The spectrum of ASAH1-related disorders ranges from Farber disease (FD) to spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME).">
|
|
<meta name="og:title" content="ASAH1-Related Disorders">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="The spectrum of ASAH1-related disorders ranges from Farber disease (FD) to spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME).">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK488189/">
|
|
<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/asah1/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK488189/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<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">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<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>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8EF8527C828CF100000000004C003B.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK488189/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/gene/arsacs/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">ASAH1-Related Disorders</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/aspm-pm/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK488189/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK488189/&text=ASAH1-Related%20Disorders"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/gene/?report=reader">Title Information</a><a href="/books/n/gene/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK488189/?report=classic">Switch to classic view</a><a href="/books/NBK488189/pdf/Bookshelf_NBK488189.pdf">PDF (528K)</a><a href="/books/NBK488189/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK488189%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8EF8527C828CF100000000004C003B.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK488189_"><span class="title" itemprop="name"><i>ASAH1</i>-Related Disorders</span></h1><p class="contribs">Dyment DA, Bennett SAL, Medin JA, et al.</p><p class="fm-aai"><a href="#_NBK488189_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 25 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="asah1.Summary" itemprop="description"><h2 id="_asah1_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>The spectrum of <i>ASAH1</i>-related disorders ranges from Farber disease (FD) to spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME).</p><ul><li class="half_rhythm"><div>Classic FD is characterized by onset in the first weeks of life of painful, progressive deformity of the major joints; palpable subcutaneous nodules of joints and mechanical pressure points; and a hoarse cry resulting from granulomas of the larynx and epiglottis. Life expectancy is usually less than two years. In the other less common types of FD, onset, severity, and primary manifestations vary.</div></li><li class="half_rhythm"><div>SMA-PME is characterized by early-childhood-onset progressive lower motor neuron disease manifest typically between ages three and seven years as proximal lower-extremity weakness, followed by progressive myoclonic and atonic seizures, tremulousness/tremor, and sensorineural hearing loss. Myoclonic epilepsy typically begins in late childhood after the onset of weakness and can include jerking of the upper limbs, action myoclonus, myoclonic status, and eyelid myoclonus. Other findings include generalized tremor, and cognitive decline. The time from disease onset to death from respiratory complications is usually five to 15 years.</div></li></ul></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of an <i>ASAH1</i>-related disorder is established in a proband with suggestive clinical findings by identification of biallelic pathogenic variants in <i>ASAH1</i> and/or decreased activity of the enzyme acid ceramidase in peripheral blood leukocytes or cultured skin fibroblasts.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations</i> is symptomatic and multidisciplinary.</p><ul><li class="half_rhythm"><div>For FD: Management may include gastrostomy tube placement, surgical removal of oral and airway granulomas, and treatment of seizures as per standard practice. Hematopoietic stem cell transplantation may be an option in affected individuals who do not have significant neurologic involvement.</div></li><li class="half_rhythm"><div>For SMA-PME: Management may include standard treatment for hearing loss, scoliosis, seizures, and tremor. Weakness can be mitigated with the use of orthotics, wheelchairs, or other assistive devices.</div></li></ul><p>
|
|
<i>Surveillance:</i>
|
|
</p><ul><li class="half_rhythm"><div>For FD: At each visit assess growth with emphasis on feeding and nutritional status; airway, joint mobility, and developmental milestones.</div></li><li class="half_rhythm"><div>For SMA-PME: At each visit monitor growth with emphasis on feeding and nutritional status, pulmonary function, back for evidence of scoliosis, strength, seizure control, functional capacity (e.g., mobility, communication); assess hearing annually.</div></li></ul></div><div><h4 class="inline">Genetic counseling.</h4><p><i>ASAH1</i>-related disorders are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Sibs with the same two pathogenic variants would be expected to have the same (or very similar) phenotype. Once the <i>ASAH1</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.</p></div></div><div id="asah1.GeneReview_Scope"><h2 id="_asah1_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Tc"><a href="/books/NBK488189/table/asah1.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobasah1Tc"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.Tc"><a href="/books/NBK488189/table/asah1.Tc/?report=objectonly" target="object" rid-ob="figobasah1Tc">Table</a></h4><p class="float-caption no_bottom_margin">Farber disease Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) <sup>1</sup></p></div></div></div><div id="asah1.Diagnosis"><h2 id="_asah1_Diagnosis_">Diagnosis</h2><div id="asah1.Suggestive_Findings"><h3>Suggestive Findings</h3><p>The following phenotypes of the <i>ASAH1</i>-related disorders <b>should be suspected</b> based on the following age-related clinical and associated findings.</p><p><b>Farber disease</b> (FD) <b>should be strongly suspected</b> in a <b>neonate or toddler</b> with the following:</p><p>
|
|
<b>Clinical findings</b>
|
|
</p><ul><li class="half_rhythm"><div>Subcutaneous nodules located at pressure points and joints</div></li><li class="half_rhythm"><div>Swollen, painful joints with progressive limitation of range of motion resulting in contractures</div></li><li class="half_rhythm"><div>Hoarse voice/cry</div></li></ul><p><b>Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME)</b>
|
|
<b>should be suspected</b> in a previously well <b>child</b> with the following:</p><p>
|
|
<b>Clinical findings</b>
|
|
</p><ul><li class="half_rhythm"><div>Normal motor and intellectual milestones</div></li><li class="half_rhythm"><div>Childhood-onset progressive, proximal muscle weakness at a mean age of five years</div></li><li class="half_rhythm"><div>Epilepsy characterized by myoclonic and atonic seizures that are refractory to treatment. Other seizure types include absence seizures and the occasional generalized tonic-clonic seizure.</div></li></ul><p>
|
|
<b>Other</b>
|
|
</p><ul><li class="half_rhythm"><div>Electromyography (EMG): evidence of chronic denervation</div></li><li class="half_rhythm"><div>Electroencephalography (EEG): generalized polyspike and wave discharges</div></li><li class="half_rhythm"><div>Muscle biopsy: evidence of a neurogenic process; absence of mitochondrial-related pathology</div></li><li class="half_rhythm"><div>Absence of biallelic pathogenic variants in <i>SMN1</i> (the cause of the most common form of <a href="/books/n/gene/sma/?report=reader">SMA</a>)</div></li></ul></div><div id="asah1.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of an <i>ASAH1</i>-related disorder <b>is established</b> in a proband with suggestive clinical findings by identification of biallelic pathogenic (or likely pathogenic) variants in <i>ASAH1</i> (see <a href="/books/NBK488189/table/asah1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobasah1Tmoleculargenetictestingusedi">Table 1</a>) and/or decreased activity of the enzyme acid ceramidase in peripheral blood leukocytes or cultured skin fibroblasts.</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#asah1.REF.richards.2015.405" rid="asah1.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>ASAH1</i> variants of uncertain significance (or of one known <i>ASAH1</i> pathogenic variant and one <i>ASAH1</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p><b>Acid ceramidase activity</b> varies in peripheral blood leukocytes or cultured skin fibroblasts from complete loss often observed in Farber disease [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>] to modest decrease (6%-32%) in SMA-PME [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>, <a class="bibr" href="#asah1.REF.gan.2015.959" rid="asah1.REF.gan.2015.959">Gan et al 2015</a>]. Note: The level of acid ceramidase activity can overlap in FD and SMA-PME.</p><p><b>Molecular genetic testing</b> approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing or a multigene panel) and <b>comprehensive</b>
|
|
<b>genomic testing</b> (typically exome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Farber disease is relatively specific, young children with the distinctive findings described in <a href="#asah1.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#asah1.Option_1">Option 1</a>). In contrast, children within the phenotypic spectrum of SMA with PME – which can in its early stages be indistinguishable from other inherited disorders with lower motor neuron weakness and/or epilepsy – are more likely to be diagnosed using genomic testing (see <a href="#asah1.Option_2">Option 2</a>).</p><div id="asah1.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of an <i>ASAH1</i>-related disorder, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>ASAH1</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, gene-targeted deletion/duplication analysis should be performed as multiexon and whole-gene deletions have been reported.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>ASAH1</i> and other genes of interest (see <a href="#asah1.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene 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 exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK488189/table/asah1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobasah1Tmoleculargenetictestingusedi">Table 1</a>).</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="asah1.Option_2"><h4>Option 2</h4><p>When the phenotype is indistinguishable from many other inherited disorders with lower motor neuron weakness and/or epilepsy, <b>comprehensive</b>
|
|
<b>genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is the best option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. <b>Exome array</b> (when clinically available) may be considered if exome sequencing is nondiagnostic.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Tmoleculargenetictestingusedi"><a href="/books/NBK488189/table/asah1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobasah1Tmoleculargenetictestingusedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.molecular_genetic_testing_used_i"><a href="/books/NBK488189/table/asah1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobasah1Tmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>ASAH1</i>-Related Disorders </p></div></div></div></div></div><div id="asah1.Clinical_Characteristics"><h2 id="_asah1_Clinical_Characteristics_">Clinical Characteristics</h2><div id="asah1.Clinical_Description"><h3>Clinical Description</h3><p><i>ASAH1</i>-related disorders comprise a spectrum that ranges from Farber disease (FD) to spinal muscular atrophy (SMA) with or without epilepsy. <i>ASAH1</i>-related disorders vary in the age of onset of manifestations, the systems affected, and severity and progression of the disease. While Farber disease has been recognized clinically and diagnosed for decades based on enzyme analysis [<a class="bibr" href="#asah1.REF.farber.1952.499" rid="asah1.REF.farber.1952.499">Farber 1952</a>, <a class="bibr" href="#asah1.REF.abulhaj.1962.221" rid="asah1.REF.abulhaj.1962.221">Abul-Haj et al 1962</a>], the recognition of <i>ASAH1</i>-related SMA and associated findings is a recent discovery based on the use of genomic testing; thus, the understanding of the latter <i>ASAH1</i>-related phenotype is still evolving.</p><p>Furthermore, although to date SMA-PME and FD have been considered to be two distinct phenotypes with differences in age of onset and primary involvement of different organ systems, a girl with features of both phenotypes illustrates the phenotypic continuum of <i>ASAH1</i>-related disorders that is possible [<a class="bibr" href="#asah1.REF.teoh.2016" rid="asah1.REF.teoh.2016">Teoh et al 2016</a>]. The individual presented at age three years with polyarticular arthritis (without subcutaneous nodules) followed by progressive motor neuron disease without seizures. At age seven years she developed cognitive deficits and a hoarse voice.</p><div id="asah1.Farber_Disease_FD"><h4>Farber Disease (FD)</h4><p>Farber disease in its classic form is an early-onset, progressive, and fatal disease. With better understanding of the natural history of FD over time, investigators have suggested categorization into several types based on age of onset, severity, and primary manifestations [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>]. Nonetheless, these Farber disease phenotypes can realistically be considered part of a continuum.</p><p><b>Type 1 FD</b> (classic FD) is characterized by the triad of (1) painful, progressive deformity of the joints of the elbows, wrists, hands, knees, and feet; (2) palpable subcutaneous nodules that tend to occur at joints and mechanical pressure points, but can occur elsewhere; and (3) a hoarse cry resulting from granulomas of the larynx and epiglottis. These findings often manifest in the first weeks of life.</p><p>Neurologic involvement, reported in a significant proportion of children, can be difficult to assess given the extent of contractures and joint deformity. Many children with type 1 FD have a lower motor neuron disease that manifests as hypotonia and muscle atrophy; EMG studies show chronic denervation [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>]. A minority of children can have infantile spasms [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>].</p><p>Other features can include a cherry red spot of the macula [<a class="bibr" href="#asah1.REF.cogan.1966.752" rid="asah1.REF.cogan.1966.752">Cogan et al 1966</a>].</p><p>Infiltrative pulmonary disease causes respiratory insufficiency that typically results in death before age two years [<a class="bibr" href="#asah1.REF.ehlert.2007.15" rid="asah1.REF.ehlert.2007.15">Ehlert et al 2007</a>, <a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>].</p><p><b>Type 2 FD</b> ("Intermediate FD") is characterized by age of onset of approximately eight months. Although the classic triad is present, the neurologic involvement is considered less severe than that of type 1 FD [<a class="bibr" href="#asah1.REF.burck.1985.203" rid="asah1.REF.burck.1985.203">Burck et al 1985</a>, <a class="bibr" href="#asah1.REF.al_jasmi.2012.533" rid="asah1.REF.al_jasmi.2012.533">Al Jasmi 2012</a>, <a class="bibr" href="#asah1.REF.chedrawi.2012.400" rid="asah1.REF.chedrawi.2012.400">Chedrawi et al 2012</a>, <a class="bibr" href="#asah1.REF.kostik.2013.1079" rid="asah1.REF.kostik.2013.1079">Kostik et al 2013</a>]. Seizures become relatively more common over time [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>].</p><p>Life expectancy is to mid-childhood.</p><p><b>Type 3 FD</b> (mild FD) is characterized by joint swelling, pain, and contractures with onset after age one year. Many of these children will be mistakenly diagnosed with a juvenile idiopathic arthritis [<a class="bibr" href="#asah1.REF.schuchman.2014.s173" rid="asah1.REF.schuchman.2014.s173">Schuchman 2014</a>]. Neurologic findings are observed in approximately half of affected children [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>]. Approximately 30% (8/25) of individuals with either type 2 FD or type 3 FD show marked cognitive deficits (IQ<80).</p><p>Life expectancy is into the teen years [<a class="bibr" href="#asah1.REF.samuelsson.1971.393" rid="asah1.REF.samuelsson.1971.393">Samuelsson & Zetterström 1971</a>, <a class="bibr" href="#asah1.REF.pavone.1980.193" rid="asah1.REF.pavone.1980.193">Pavone et al 1980</a>, <a class="bibr" href="#asah1.REF.fiumara.1993.915" rid="asah1.REF.fiumara.1993.915">Fiumara et al 1993</a>].</p><p><b>Type 4 FD</b> (neonatal-visceral FD) is characterized by neonatal severe hepatosplenomegaly without the classic triad [<a class="bibr" href="#asah1.REF.cartigny.1985.8" rid="asah1.REF.cartigny.1985.8">Cartigny et al 1985</a>, <a class="bibr" href="#asah1.REF.qualman.1987.233" rid="asah1.REF.qualman.1987.233">Qualman et al 1987</a>, <a class="bibr" href="#asah1.REF.kattner.1997.292" rid="asah1.REF.kattner.1997.292">Kattner et al 1997</a>].</p><p>Death occurs within the first days to weeks of life.</p><p><b>Type 5 FD</b> (neurologic FD) is characterized by six to 12 months of normal development followed by refractory seizures, progressive paraparesis, and speech regression [<a class="bibr" href="#asah1.REF.eviatar.1986.371" rid="asah1.REF.eviatar.1986.371">Eviatar et al 1986</a>, <a class="bibr" href="#asah1.REF.jameson.1987.559" rid="asah1.REF.jameson.1987.559">Jameson et al 1987</a>].</p><p>Subcutaneous nodules can be present, but are usually mild. Lung infiltration and hepatosplenomegaly do not occur.</p><p><b>Diagnosis of FD prior to the availability of <i>ASAH1</i> molecular genetic testing.</b> The diagnosis of FD was formerly based on histologic and biochemical findings in individuals with a typical clinical presentation [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>]. Biopsy of the subcutaneous nodules can show characteristic curvilinear granulomatous infiltrations or "Farber bodies" under light microscopy in macrophages, histiocytes, foam cells, and fibroblasts [<a class="bibr" href="#asah1.REF.schmoeckel.1980.153" rid="asah1.REF.schmoeckel.1980.153">Schmoeckel 1980</a>, <a class="bibr" href="#asah1.REF.burck.1985.203" rid="asah1.REF.burck.1985.203">Burck et al 1985</a>].</p></div><div id="asah1.Spinal_Muscular_Atrophy_with_Progr"><h4>Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME)</h4><p>SMA-PME is characterized by early-childhood onset of progressive proximal weakness followed by progressive myoclonic and atonic seizures, tremulousness/tremor, and sensorineural hearing loss [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>, <a class="bibr" href="#asah1.REF.gan.2015.959" rid="asah1.REF.gan.2015.959">Gan et al 2015</a>, <a class="bibr" href="#asah1.REF.topaloglu.2016.128" rid="asah1.REF.topaloglu.2016.128">Topaloglu & Melki 2016</a>].</p><p><b>Lower motor neuron disease,</b> the first manifestation in the majority of affected individuals (16/17), is typically evident as weakness between ages three and seven years (median 5 years; range 17 months [<a class="bibr" href="#asah1.REF.rubboli.2015.692" rid="asah1.REF.rubboli.2015.692">Rubboli et al 2015</a>] to 15 years [<a class="bibr" href="#asah1.REF.dyment.2014.558" rid="asah1.REF.dyment.2014.558">Dyment et al 2014</a>]). Initially weakness is proximal, and progresses from initial clumsiness/frequent falls to a waddling gait and need for assistive devices for walking.</p><p>The lower motor neuron disease also involves the muscles of respiration; thus, recurrent aspiration pneumonias are common (6/16).</p><p><b>Epilepsy.</b> Although seizures often begin in late childhood, after the onset of weakness, exceptions occur [<a class="bibr" href="#asah1.REF.filosto.2016.1578" rid="asah1.REF.filosto.2016.1578">Filosto et al 2016</a>, <a class="bibr" href="#asah1.REF.topaloglu.2016.128" rid="asah1.REF.topaloglu.2016.128">Topaloglu & Melki 2016</a>].</p><p>Myoclonic seizures, which begin as jerking of the upper limbs, are more proximal than distal. Action myoclonus, myoclonic status, and eyelid myoclonus have also been reported [<a class="bibr" href="#asah1.REF.rubboli.2015.692" rid="asah1.REF.rubboli.2015.692">Rubboli et al 2015</a>, <a class="bibr" href="#asah1.REF.oguz_akarsu.2016.49" rid="asah1.REF.oguz_akarsu.2016.49">Oguz Akarsu et al 2016</a>]. Progressive increase in frequency of the myoclonus contributes significantly to the decreasing motor function [<a class="bibr" href="#asah1.REF.dyment.2014.558" rid="asah1.REF.dyment.2014.558">Dyment et al 2014</a>, <a class="bibr" href="#asah1.REF.rubboli.2015.692" rid="asah1.REF.rubboli.2015.692">Rubboli et al 2015</a>].</p><p>Atonic seizures of the head and/or torso are also an early presenting seizure type.</p><p>Absence seizures are observed in more than half of affected individuals [<a class="bibr" href="#asah1.REF.gan.2015.959" rid="asah1.REF.gan.2015.959">Gan et al 2015</a>].</p><p>Although reported, generalized tonic-clonic seizures are less common than the other types.</p><p>Seizures vary in frequency from a few per day initially to a few per minute as the disease evolves. Over time, seizures become refractory to treatment.</p><p>Brain MRI is normal.</p><p><b>A generalized tremor,</b> sometimes described as overall tremulousness, has been observed in eight of 16 affected individuals reported to date.</p><p><b>Sensorineural hearing loss (SNHL)</b> that ranges from mild to profound hearing loss at high frequencies has been reported in four of 16 affected individuals [<a class="bibr" href="#asah1.REF.dyment.2014.558" rid="asah1.REF.dyment.2014.558">Dyment et al 2014</a>, <a class="bibr" href="#asah1.REF.gan.2015.959" rid="asah1.REF.gan.2015.959">Gan et al 2015</a>]. The hearing loss was not present at birth.</p><p><b>Musculoskeletal.</b> Scoliosis, observed in five of 16 individuals, ranged from mild [<a class="bibr" href="#asah1.REF.rubboli.2015.692" rid="asah1.REF.rubboli.2015.692">Rubboli et al 2015</a>] to more severe [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>].</p><p><b>Cognition.</b> Early developmental milestones are typically achieved on time. Cognition is described as normal; however, one child with intellectual disability has been reported [<a class="bibr" href="#asah1.REF.rubboli.2015.692" rid="asah1.REF.rubboli.2015.692">Rubboli et al 2015</a>].</p><p>A decline in cognitive ability has been described in children in the last weeks of disease.</p><p>In one child progressive cognitive decline was the first manifestation [<a class="bibr" href="#asah1.REF.sathe.2013.s93" rid="asah1.REF.sathe.2013.s93">Sathe & Pearson 2013</a>].</p><p><b>Life expectancy</b> is shortened. The time from disease onset to death has ranged from five to 15 years. Although most affected children die in their late teens [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>], some individuals who have been symptomatic for more than two decades have lived into their twenties [<a class="bibr" href="#asah1.REF.gan.2015.959" rid="asah1.REF.gan.2015.959">Gan et al 2015</a>, <a class="bibr" href="#asah1.REF.filosto.2016.1578" rid="asah1.REF.filosto.2016.1578">Filosto et al 2016</a>, <a class="bibr" href="#asah1.REF.kernohan.2017.611" rid="asah1.REF.kernohan.2017.611">Kernohan et al 2017</a>]</p></div><div id="asah1.ASAH1Related_Spinal_Muscular_Atrop"><h4><i>ASAH1</i>-Related Spinal Muscular Atrophy without Epilepsy</h4><p>Two sibs in one family have been reported with childhood-onset <i>ASAH1</i>-related spinal muscular atrophy [<a class="bibr" href="#asah1.REF.filosto.2016.1578" rid="asah1.REF.filosto.2016.1578">Filosto et al 2016</a>] without any history of seizures or myoclonus. As adults, the sibs had mild proximal weakness that caused difficulty with walking. Both had scoliosis and a postural tremor. Fasciculation, contractures, and pulmonary disease/respiratory insufficiency were not observed. Sensorineural hearing loss was not reported [<a class="bibr" href="#asah1.REF.filosto.2016.1578" rid="asah1.REF.filosto.2016.1578">Filosto et al 2016</a>].</p></div><div id="asah1.Progressive_AdultOnset_Brachydacty"><h4>Progressive Adult-Onset Brachydactyly Due to Osteolysis</h4><p>A progressive adult-onset brachydactyly due to osteolysis has been reported in a single family with three affected family members who had progressive shortening of the fingers and toes due to severe osteolysis. Both reduced acid ceramidase activity and biallelic <i>ASAH1</i> pathogenic variants segregated with the phenotype in the family [<a class="bibr" href="#asah1.REF.bonaf_.2016.2323" rid="asah1.REF.bonaf_.2016.2323">Bonafé et al 2016</a>].</p></div></div><div id="asah1.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No obvious genotype-phenotype correlations have been observed in <i>ASAH1</i>-related disorder to date despite a predominance of nonsense and splice-site variants in SMA-PME and a predominance of missense variants in FD.</p><p>While recurrent pathogenic variants have been observed in the FD phenotype (e.g., <a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus">c.703G>C</a>) and the SMA-PME phenotype (e.g., <a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus">c.125C>T</a>), to date the only <i>ASAH1</i> pathogenic variants observed in both phenotypes are those that result in skipping of exon 6 [<a class="bibr" href="#asah1.REF.b_r.2001.199" rid="asah1.REF.b_r.2001.199">Bär et al 2001</a>, <a class="bibr" href="#asah1.REF.bashyam.2014.530" rid="asah1.REF.bashyam.2014.530">Bashyam et al 2014</a>, <a class="bibr" href="#asah1.REF.dyment.2014.558" rid="asah1.REF.dyment.2014.558">Dyment et al 2014</a>].</p><p>There is a correlation in FD between age of death, in situ acid ceramidase activity, and the amount of ceramide accumulation [<a class="bibr" href="#asah1.REF.levade.1995.108" rid="asah1.REF.levade.1995.108">Levade et al 1995</a>].</p></div><div id="asah1.Nomenclature"><h3>Nomenclature</h3><p>Farber disease may also be referred to as "acid ceramidase deficiency," "Farber lipogranulomatosis," or "disseminated lipogranulomatosis."</p><p>Spinal muscular atrophy with progressive myoclonic epilepsy may also be referred to as "myoclonus with progressive distal muscular atrophy."</p></div><div id="asah1.Prevalence"><h3>Prevalence</h3><p>No known specific prevalence estimates exist for <i>ASAH1</i>-related disorders (recognized primarily as FD or SMA-PME). The disorders are ultra-rare and estimated to occur in fewer than one per million (<a href="https://www.orpha.net" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.orpha.net</a>).</p></div></div><div id="asah1.Genetically_Related_Allelic_Disord"><h2 id="_asah1_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>ASAH1</i>.</p></div><div id="asah1.Differential_Diagnosis"><h2 id="_asah1_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Tinheriteddisorderstoconsider"><a href="/books/NBK488189/table/asah1.T.inherited_disorders_to_consider/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobasah1Tinheriteddisorderstoconsider"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.inherited_disorders_to_consider"><a href="/books/NBK488189/table/asah1.T.inherited_disorders_to_consider/?report=objectonly" target="object" rid-ob="figobasah1Tinheriteddisorderstoconsider">Table 2. </a></h4><p class="float-caption no_bottom_margin">Inherited Disorders to Consider in the Differential Diagnosis of <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME) </p></div></div></div><div id="asah1.Management"><h2 id="_asah1_Management_">Management</h2><div id="asah1.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with an <i>ASAH1</i>-related disorder, the evaluations summarized in <a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedevaluationsfollowin">Table 3a</a> and <a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin_1/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedevaluationsfollowin1">Table 3b</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Trecommendedevaluationsfollowin"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin/?report=objectonly" target="object" title="Table 3a. " class="img_link icnblk_img" rid-ob="figobasah1Trecommendedevaluationsfollowin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.recommended_evaluations_followin"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedevaluationsfollowin">Table 3a. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis of an <i>ASAH1</i>-Related Disorder: Farber Disease </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Trecommendedevaluationsfollowin1"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin_1/?report=objectonly" target="object" title="Table 3b. " class="img_link icnblk_img" rid-ob="figobasah1Trecommendedevaluationsfollowin1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.recommended_evaluations_followin_1"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin_1/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedevaluationsfollowin1">Table 3b. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis of an <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME) </p></div></div></div><div id="asah1.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Treatment for those with FD and SMA-PME is symptomatic and multidisciplinary.</p><p>There is no curative treatment; measures that can improve the individual's quality of life are summarized in <a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" rid-ob="figobasah1Ttreatmentofmanifestationsini">Table 4a</a> and <a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i_1/?report=objectonly" target="object" rid-ob="figobasah1Ttreatmentofmanifestationsini1">Table 4b</a>. Depending on the age and presenting problems of the individual with an <i>ASAH1</i>-related disorder, a multidisciplinary evaluation involving health care providers from the following specialties is often necessary:</p><ul><li class="half_rhythm"><div><b>FD.</b> Rheumatology, neurology, general pediatrics, pain specialists, ENT and palliative care</div></li><li class="half_rhythm"><div><b>SMA-PME.</b> Neurology, physical medicine and rehabilitation, feeding/gastroenterology, general pediatrics, audiology, clinical genetics, ophthalmology, and palliative care</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Ttreatmentofmanifestationsini"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" title="Table 4a. " class="img_link icnblk_img" rid-ob="figobasah1Ttreatmentofmanifestationsini"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.treatment_of_manifestations_in_i"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" rid-ob="figobasah1Ttreatmentofmanifestationsini">Table 4a. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>ASAH1</i>-Related Disorder: Farber Disease </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Ttreatmentofmanifestationsini1"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i_1/?report=objectonly" target="object" title="Table 4b. " class="img_link icnblk_img" rid-ob="figobasah1Ttreatmentofmanifestationsini1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.treatment_of_manifestations_in_i_1"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i_1/?report=objectonly" target="object" rid-ob="figobasah1Ttreatmentofmanifestationsini1">Table 4b. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME) </p></div></div><div id="asah1.Adaptive_Disabilities"><h4>Adaptive Disabilities</h4><p>Note: The following information represents typical management recommendations for individuals with adaptive disabilities in the United States; standard recommendations may vary from country to country.</p><p>Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.</p><p>Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</p><p>In the US:</p><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="asah1.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p><b>Gross motor dysfunction.</b> Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</p><p><b>Oral motor dysfunction.</b> Assuming that the individual is safe to eat by mouth, feeding therapy – typically from an occupational or speech therapist – is recommended for affected individuals who have difficulty feeding due to poor oral motor control.</p></div></div><div id="asah1.Surveillance"><h3>Surveillance</h3><p>No guidelines have been published for the surveillance of <i>ASAH1</i>-related disorder.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Trecommendedsurveillanceforind"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind/?report=objectonly" target="object" title="Table 5a. " class="img_link icnblk_img" rid-ob="figobasah1Trecommendedsurveillanceforind"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.recommended_surveillance_for_ind"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedsurveillanceforind">Table 5a. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>ASAH1</i>-Related Disorder: Farber Disease </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Trecommendedsurveillanceforind1"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind_1/?report=objectonly" target="object" title="Table 5b. " class="img_link icnblk_img" rid-ob="figobasah1Trecommendedsurveillanceforind1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.recommended_surveillance_for_ind_1"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind_1/?report=objectonly" target="object" rid-ob="figobasah1Trecommendedsurveillanceforind1">Table 5b. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>ASAH1</i>-Related Disorder: SMA-PME </p></div></div></div><div id="asah1.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#asah1.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="asah1.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Acid ceramidase cDNA introduced into mice in a viral vector has been shown to be expressed over an extended period of time [<a class="bibr" href="#asah1.REF.ramsubir.2008.133" rid="asah1.REF.ramsubir.2008.133">Ramsubir et al 2008</a>]. Further, the expressed acid ceramidase was able to ameliorate the manifestations in a mouse model of Farber disease [<a class="bibr" href="#asah1.REF.alayoubi.2013.827" rid="asah1.REF.alayoubi.2013.827">Alayoubi et al 2013</a>].</p><p>Acid ceramidase introduced safely into in non-human, myelo-ablated primates using a lentiviral vector was successfully expressed in hematopoietic cells [<a class="bibr" href="#asah1.REF.walia.2011.679" rid="asah1.REF.walia.2011.679">Walia et al 2011</a>].</p><p>
|
|
<b>Enzyme replacement therapy</b>
|
|
</p><ul><li class="half_rhythm"><div>Human recombinant acid ceramidase reduced ceramide levels in the fibroblasts of an individual with Farber disease [<a class="bibr" href="#asah1.REF.he.2017.85" rid="asah1.REF.he.2017.85">He et al 2017</a>].</div></li><li class="half_rhythm"><div>Recombinant acid ceramidase treatment of the mouse model resulted in no further accumulation of ceramide and improved survival [<a class="bibr" href="#asah1.REF.he.2017.85" rid="asah1.REF.he.2017.85">He et al 2017</a>].</div></li></ul><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.</p></div></div><div id="asah1.Genetic_Counseling"><h2 id="_asah1_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="asah1.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>ASAH1</i>-related disorders are inherited in an autosomal recessive manner.</p><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., carriers of one <i>ASAH1</i> pathogenic variant).</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>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Sibs with the same two pathogenic variants would be expected to have the same (or very similar) phenotype.</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 proband.</b> The offspring of an individual with an <i>ASAH1</i>-related disorder would be expected to be obligate heterozygotes (carriers) for a pathogenic variant in <i>ASAH1</i>. However, fertility is unknown, as the only affected individual known to have reproduced to date was a woman with atypical SMA without seizures, diagnosed in the first trimester of pregnancy [<a class="bibr" href="#asah1.REF.filosto.2016.1578" rid="asah1.REF.filosto.2016.1578">Filosto et al 2016</a>].</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>ASAH1</i> pathogenic variant.</p></div><div id="asah1.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ASAH1</i> pathogenic variants in the family.</p></div><div id="asah1.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are carriers or are at risk of being carriers.</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="bibr" href="#asah1.REF.huang.2022.389" rid="asah1.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="asah1.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ASAH1</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="asah1.Resources"><h2 id="_asah1_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/?report=reader">here</a>.</i></p>
|
|
<ul><li class="half_rhythm"><div>
|
|
<b>National Library of Medicine Genetics Home Reference</b>
|
|
</div><div>
|
|
<a href="https://ghr.nlm.nih.gov/condition/farberlipogranulomatosis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Farber lipogranulomatosis</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>American Epilepsy Society</b>
|
|
</div><div>
|
|
<a href="https://www.aesnet.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aesnet.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Epilepsy Foundation</b>
|
|
</div><div><b>Phone:</b> 800-332-1000; 866-748-8008</div><div>
|
|
<a href="https://www.epilepsy.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.com</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>Muscular Dystrophy Association (MDA) - USA</b>
|
|
</div><div><b>Phone:</b> 833-275-6321</div><div><b>Email:</b> ResourceCenter@mdausa.org</div><div>
|
|
<a href="http://www.mda.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">mda.org</a>
|
|
</div></li></ul>
|
|
</div><div id="asah1.Molecular_Genetics"><h2 id="_asah1_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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1molgenTA"><a href="/books/NBK488189/table/asah1.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobasah1molgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.molgen.TA"><a href="/books/NBK488189/table/asah1.molgen.TA/?report=objectonly" target="object" rid-ob="figobasah1molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">ASAH1-Related Disorders: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1molgenTB"><a href="/books/NBK488189/table/asah1.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobasah1molgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.molgen.TB"><a href="/books/NBK488189/table/asah1.molgen.TB/?report=objectonly" target="object" rid-ob="figobasah1molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for ASAH1-Related Disorders (View All in OMIM) </p></div></div><p><b>Gene structure.</b> The primary <i>ASAH1</i> transcript (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_177924.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_177924.5</a>) comprises 14 exons spanning 30 kb [<a class="bibr" href="#asah1.REF.li.1999.223" rid="asah1.REF.li.1999.223">Li et al 1999</a>]. Multiple transcript variants that encode different isoforms are known. See <a href="/books/NBK488189/?report=reader#asah1.molgen.TA">Table A</a>, <b>Gene</b> for a detailed summary of gene and protein information.</p><p><b>Pathogenic variants.</b> To date 46 pathogenic variants have been reported [<a class="bibr" href="#asah1.REF.stenson.2014.1" rid="asah1.REF.stenson.2014.1">Stenson et al 2014</a>].</p><p>Two reported gross deletions include:</p><ul><li class="half_rhythm"><div>A 55-kb deletion including all of <i>ASAH1</i> [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>];</div></li><li class="half_rhythm"><div>A 9,471-bp deletion including exons 3-5 (c.126-3941_382+1358del) [<a class="bibr" href="#asah1.REF.alves.2013.276" rid="asah1.REF.alves.2013.276">Alves et al 2013</a>].</div></li></ul><p>Cellular ceramide levels, which are increased from two- to fivefold for <i>ASAH1</i>-related disorders, can provide further evidence that variants identified by <i>ASAH1</i> sequencing are pathogenic [<a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>, <a class="bibr" href="#asah1.REF.kernohan.2017.611" rid="asah1.REF.kernohan.2017.611">Kernohan et al 2017</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figasah1Tasah1pathogenicvariantsdiscus"><a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="asah1.T.asah1_pathogenic_variants_discus"><a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>ASAH1</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
|
|
<i>ASAH1</i> encodes a 395-amino acid protein, N-acylsphingosine amidohydrolase (acid ceramidase) [<a class="bibr" href="#asah1.REF.koch.1996.33110" rid="asah1.REF.koch.1996.33110">Koch et al 1996</a>] (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_808592.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_808592.2</a>). The 53-55 kd precursor protein is self-cleaved into both an alpha and beta subunit at position Cys143. The alpha subunit is 13 kd and not glycosylated; the beta subunit is 27 kd and glycosylated [<a class="bibr" href="#asah1.REF.shtraizent.2008.11253" rid="asah1.REF.shtraizent.2008.11253">Shtraizent et al 2008</a>]. The Cys143 is then able to serve as a site for the hydrolysis of ceramide [<a class="bibr" href="#asah1.REF.shtraizent.2008.11253" rid="asah1.REF.shtraizent.2008.11253">Shtraizent et al 2008</a>].</p><p>Acid ceramidase catalyzes the breakdown of ceramide into sphingosine and fatty acid within the acidic lysosome; it can also perform the reverse reaction and synthesize ceramide at neutral pH. The substrate, ceramide, is an important sphingolipid with a role in signal transmission and cell recognition [<a class="bibr" href="#asah1.REF.alayoubi.2013.827" rid="asah1.REF.alayoubi.2013.827">Alayoubi et al 2013</a>].</p><p><b>Abnormal gene product.</b> Absence of or reduction in acid ceramidase activity results in an accumulation of ceramide in the lysosomes of most tissues [<a class="bibr" href="#asah1.REF.koga.1992.42" rid="asah1.REF.koga.1992.42">Koga et al 1992</a>, <a class="bibr" href="#asah1.REF.levade.2009" rid="asah1.REF.levade.2009">Levade et al 2009</a>]. The expected downstream consequences of accumulated ceramide include increased levels of monocyte chemotactic protein-1 (MCP1), a pro-inflammatory chemokine that attracts monocytes to sites of tissue infection and injury [<a class="bibr" href="#asah1.REF.alayoubi.2013.827" rid="asah1.REF.alayoubi.2013.827">Alayoubi et al 2013</a>].</p></div><div id="asah1.Chapter_Notes"><h2 id="_asah1_Chapter_Notes_">Chapter Notes</h2><div id="asah1.Author_Notes"><h3>Author Notes</h3><p><b>David Dyment, DPhil, MD</b> is a clinical geneticist with a University of Ottawa Clinical Research Chair in Epilepsy Genetics. His research focus is neurogenetics and epilepsy and the application of new technologies to clinical practice.</p><p>Website: <a href="https://care4rare.ca/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">care4rare.ca</a></p><p><b>Stef Bennett, PhD</b> is a recipient of a University Chair in Neurolipidomics in the Department of Biochemistry, Microbiology, and Immunology at the University of Ottawa. Her research career is focused on how lipids can be used to diagnose early, track the disease course, and ultimately be modified with repurposed compounds to treat neurodegenerative disease.</p><p>Website: <a href="http://www.med.uottawa.ca/lipidomics" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.med.uottawa.ca/lipidomics</a></p><p><b>Thierry Levade, MD, PhD</b> is a clinical biochemist at the Paul Sabatier Toulouse University and Hospital. His research, conducted at the Cancer Research Center of Toulouse, focuses on sphingolipids in health and disease.</p><p>Website: <a href="http://www.crct-inserm.fr/en/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.crct-inserm.fr</a></p><p><b>Jeffrey A Medin, PhD</b> holds the MACC Fund Endowed Chair in Pediatrics and Biochemistry at the Medical College of Wisconsin in Milwaukee. He also maintains an Affiliate Scientist position at the University Health Network in Toronto. He has worked on the development of models and implementation of novel therapies for lysosomal storage disorders for many years.</p><p>Website: <a href="https://www.mcw.edu/departments/pediatrics/divisions/hematology-oncology-blood-and-marrow-transplant/research" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.mcw.edu/Pediatrics</a></p></div><div id="asah1.Acknowledgments"><h3>Acknowledgments</h3><p>The authors would like to acknowledge Dr Ed Schuchman for helpful discussion and advice.</p></div><div id="asah1.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>29 March 2018 (bp) Review posted live</div></li><li class="half_rhythm"><div>26 June 2017 (dad) Original submission</div></li></ul></div></div><div id="asah1.References"><h2 id="_asah1_References_">References</h2><div id="asah1.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.abulhaj.1962.221">Abul-Haj SK, Martz DG, Douglas WF, Geppert LJ. Farber's disease. Report of a case with observations on its histogenesis and notes on the nature of the stored material. <span><span class="ref-journal">J Pediatr. </span>1962;<span class="ref-vol">61</span>:221–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/13859108" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13859108</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.al_jasmi.2012.533">Al Jasmi F. A novel mutation in an atypical presentation of the rare infantile Farber disease. <span><span class="ref-journal">Brain Dev. </span>2012;<span class="ref-vol">34</span>:533–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21982811" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21982811</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.alayoubi.2013.827">Alayoubi AM, Wang JC, Au BC, Carpentier S, Garcia V, Dworski S, El-Ghamrasni S, Kirouac KN, Exertier MJ, Xiong ZJ, Privé GG, Simonaro CM, Casas J, Fabrias G, Schuchman EH, Turner PV, Hakem R, Levade T, Medin JA. Systemic ceramide accumulation leads to severe and varied pathological consequences. <span><span class="ref-journal">EMBO Mol Med. </span>2013;<span class="ref-vol">5</span>:827–42.</span> [<a href="/pmc/articles/PMC3779446/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3779446</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23681708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23681708</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.alves.2013.276">Alves MQ, Le Trionnaire E, Ribeiro I, Carpentier S, Harzer K, Levade T, Ribeiro MG. Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene. <span><span class="ref-journal">Mol Genet Metab. </span>2013;<span class="ref-vol">109</span>:276–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23707712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23707712</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.b_r.2001.199">Bär J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K. Molecular analysis of acid ceramidase deficiency in patients with Farber disease. <span><span class="ref-journal">Hum Mutat. </span>2001;<span class="ref-vol">17</span>:199–209.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11241842" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11241842</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.bashyam.2014.530">Bashyam MD, Chaudhary AK, Kiran M, Reddy V, Nagarajaram HA, Dalal A, Bashyam L, Suri D, Gupta A, Gupta N, Kabra M, Puri RD, Rama Devi R, Kapoor S, Danda S. Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: analyses of exonic splicing enhancer inactivating mutation. <span><span class="ref-journal">Clin Genet. </span>2014;<span class="ref-vol">86</span>:530–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24355074" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24355074</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.bonaf_.2016.2323">Bonafé L, Kariminejad A, Li J, Royer-Bertrand B, Garcia V, Mahdavi S, Bozorgmehr B, Lachman RL, Mittaz-Crettol L, Campos-Xavier B, Nampoothiri S, Unger S, Rivolta C, Levade T, Superti-Furga A. Brief report: peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: a new presentation of Farber's disease. <span><span class="ref-journal">Arthritis Rheumatol. </span>2016;<span class="ref-vol">68</span>:2323–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26945816" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26945816</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.burck.1985.203">Burck U, Moser HW, Goebel HH, Grüttner R, Held KR. A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects. <span><span class="ref-journal">Eur J Pediatr. </span>1985;<span class="ref-vol">143</span>:203–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3987715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3987715</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.cappellari.2016.149">Cappellari AM, Torcoletti M, Triulzi F, Corona F. Nervous system involvement in Farber disease. <span><span class="ref-journal">J Inherit Metab Dis. </span>2016;<span class="ref-vol">39</span>:149–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26373951" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26373951</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.cartigny.1985.8">Cartigny B, Libert J, Fensom AH, Martin JJ, Dhondt JL, Wyart D, Fontaine G, Farriaux JP. Clinical diagnosis of a new case of ceramidase deficiency (Farber's disease). <span><span class="ref-journal">J Inherit Metab Dis. </span>1985;<span class="ref-vol">8</span>:8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3921761" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3921761</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.chedrawi.2012.400">Chedrawi AK, Al-Hassnan ZN, Al-Muhaizea M, Colak D, Al-Younes B, Albakheet A, Tulba S, Kaya N. Novel V97G ASAH1 mutation found in Farber disease patients: unique appearance of the disease with an intermediate severity, and marked early involvement of central and peripheral nervous system. <span><span class="ref-journal">Brain Dev. </span>2012;<span class="ref-vol">34</span>:400–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21893389" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21893389</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.cogan.1966.752">Cogan DG, Kuwabara T, Moser H, Hazard GW. Retinopathy in a case of Farber's lipogranulomatosis. <span><span class="ref-journal">Arch Ophthalmol. </span>1966;<span class="ref-vol">75</span>:752–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/5936802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5936802</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.dyment.2014.558">Dyment DA, Sell E, Vanstone MR, Smith AC, Garandeau D, Garcia V, Carpentier S, Le Trionnaire E, Sabourdy F, Beaulieu CL, Schwartzentruber JA, McMillan HJ, Majewski J, Bulman DE, Levade T, Boycott KM, et al. Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy. <span><span class="ref-journal">Clin Genet. </span>2014;<span class="ref-vol">86</span>:558–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24164096" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24164096</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.ehlert.2007.15">Ehlert K, Frosch M, Fehse N, Zander A, Roth J, Vormoor J. Farber disease: clinical presentation, pathogenesis and a new approach to treatment. <span><span class="ref-journal">Pediatr Rheumatol Online J. </span>2007;<span class="ref-vol">5</span>:15.</span> [<a href="/pmc/articles/PMC1920510/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1920510</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17603888" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17603888</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.eviatar.1986.371">Eviatar L, Sklower SL, Wisniewski K, Feldman RS, Gochoco A. Farber lipogranulomatosis: an unusual presentation in a black child. <span><span class="ref-journal">Pediatr Neurol. </span>1986;<span class="ref-vol">2</span>:371–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2854742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2854742</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.farber.1952.499">Farber S. A lipid metabolic disorder: disseminated lipogranulomatosis; a syndrome with similarity to, and important difference from, Niemann-Pick and Hand-Schüller-Christian disease. <span><span class="ref-journal">AMA Am J Dis Child. </span>1952;<span class="ref-vol">84</span>:499–500.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12975849" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12975849</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.filosto.2016.1578">Filosto M, Aureli M, Castellotti B, Rinaldi F, Schiumarini D, Valsecchi M, Lualdi S, Mazzotti R, Pensato V, Rota S, Gellera C, Filocamo M, Padovani A. ASAH1 variant causing a mild SMA phenotype with no myoclonic epilepsy: a clinical, biochemical and molecular study. <span><span class="ref-journal">Eur J Hum Genet. </span>2016;<span class="ref-vol">24</span>:1578–83.</span> [<a href="/pmc/articles/PMC5110045/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5110045</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27026573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27026573</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.fiumara.1993.915">Fiumara A, Nigro F, Pavone L, Moser HW. Farber disease with prolonged survival. <span><span class="ref-journal">J Inherit Metab Dis. </span>1993;<span class="ref-vol">16</span>:915–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8295420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8295420</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.gan.2015.959">Gan JJ, Garcia V, Tian J, Tagliati M, Parisi JE, Chung JM, Lewis R, Baloh R, Levade T, Pierson TM. Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy. <span><span class="ref-journal">Neuromuscul Disord. </span>2015;<span class="ref-vol">25</span>:959–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26526000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26526000</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.haraoka.1997.405">Haraoka G, Muraoka M, Yoshioka N, Wakami S, Hayashi I. First case of surgical treatment of Farber's disease. <span><span class="ref-journal">Ann Plast Surg. </span>1997;<span class="ref-vol">39</span>:405–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9339283" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9339283</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.he.2017.85">He X, Dworski S, Zhu C, DeAngelis V, Solyom A, Medin JA, Simonaro CM, Schuchman EH. Enzyme replacement therapy for Farber disease: Proof-of-concept studies in cells and mice. <span><span class="ref-journal">BBA Clin. </span>2017;<span class="ref-vol">7</span>:85–96.</span> [<a href="/pmc/articles/PMC5338723/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5338723</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28275553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28275553</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.huang.2022.389">Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. <span><span class="ref-journal">J Community Genet. </span>2022;<span class="ref-vol">13</span>:389–97.</span> [<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></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.jameson.1987.559">Jameson RA, Holt PJ, Keen JH. Farber's disease (lysosomal acid ceramidase deficiency). <span><span class="ref-journal">Ann Rheum Dis. </span>1987;<span class="ref-vol">46</span>:559–61.</span> [<a href="/pmc/articles/PMC1002193/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1002193</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/3662645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3662645</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.jarisch.2014.1399">Jarisch A, Steward CG, Sörensen J, Porto L, Kieslich M, Klingebiel T, Bader P. Odontoid infiltration and spinal compression in Farber Disease: reversal by haematopoietic stem cell transplantation. <span><span class="ref-journal">Eur J Pediatr. </span>2014;<span class="ref-vol">173</span>:1399–403.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23881344" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23881344</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.kattner.1997.292">Kattner E, Schäfer A, Harzer K. Hydrops fetalis: manifestation in lysosomal storage diseases including Farber disease. <span><span class="ref-journal">Eur J Pediatr. </span>1997;<span class="ref-vol">156</span>:292–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9128814" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9128814</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.kernohan.2017.611">Kernohan KD, Frésard L, Zappala Z, Hartley T, Smith KS, Wagner J, Xu H, McBride A, Bourque PR, Consortium CRC, Bennett SAL, Dyment DA, Boycott KM, Montgomery SB, Warman Chardon J. Whole-transcriptome sequencing in blood provides a diagnosis of spinal muscular atrophy with progressive myoclonic epilepsy. <span><span class="ref-journal">Hum Mutat. </span>2017;<span class="ref-vol">38</span>:611–4.</span> [<a href="/pmc/articles/PMC5889109/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5889109</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28251733" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28251733</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.koch.1996.33110">Koch J, Gärtner S, Li CM, Quintern LE, Bernardo K, Levran O, Schnabel D, Desnick RJ, Schuchman EH, Sandhoff K. Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification Of the first molecular lesion causing Farber disease. <span><span class="ref-journal">J Biol Chem. </span>1996;<span class="ref-vol">271</span>:33110–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8955159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8955159</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.koga.1992.42">Koga M, Ishihara T, Uchino F, Fujiwaki T. An autopsy case of Farber's lipogranulomatosis in a Japanese boy with gastrointestinal involvement. <span><span class="ref-journal">Acta Pathol Jpn. </span>1992;<span class="ref-vol">42</span>:42–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1557987" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1557987</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.kostik.2013.1079">Kostik MM, Chikova IA, Avramenko VV, Vasyakina LI, Le Trionnaire E, Chasnyk VG, Levade T. Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis. <span><span class="ref-journal">J Inherit Metab Dis. </span>2013;<span class="ref-vol">36</span>:1079–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23385296" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23385296</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.levade.1995.108">Levade T, Moser HW, Fensom AH, Harzer K, Moser AB, Salvayre R. Neurodegenerative course in ceramidase deficiency (Farber disease) correlates with the residual lysosomal ceramide turnover in cultured living patient cells. <span><span class="ref-journal">J Neurol Sci. </span>1995;<span class="ref-vol">134</span>:108–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8747852" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8747852</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.levade.2009">Levade T, Sandhoff K, Schulze H, Medin JA. Acid ceramidase deficiency: Farber lipogranulomatosis. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, eds. <em>Online Metabolic & Molecular Bases of Inherited Disease (OMMBID).</em> McGraw-Hill. 2009.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.li.1999.223">Li CM, Park JH, He X, Levy B, Chen F, Arai K, Adler DA, Disteche CM, Koch J, Sandhoff K, Schuchman EH. The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression. <span><span class="ref-journal">Genomics. </span>1999;<span class="ref-vol">62</span>:223–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10610716" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10610716</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.oguz_akarsu.2016.49">Oguz Akarsu E, Tekturk P, Yapici Z, Tepgec F, Uyguner ZO, Baykan B. Eyelid myoclonic status epilepticus: A rare phenotype in spinal muscular atrophy with progressive myoclonic epilepsy associated with ASAH1 gene mutation. <span><span class="ref-journal">Seizure. </span>2016;<span class="ref-vol">42</span>:49–51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27723502" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27723502</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.pavone.1980.193">Pavone L, Moser HW, Mollica F, Reitano C, Durand P. Farber's lipogranulomatosis: ceramidase deficiency and prolonged survival in three relatives. <span><span class="ref-journal">Johns Hopkins Med J. </span>1980;<span class="ref-vol">147</span>:193–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7441940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7441940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.qualman.1987.233">Qualman SJ, Moser HW, Valle D, Moser AE, Antonarakis SE, Boitnott JK, Zinkham WH. Farber disease: pathologic diagnosis in sibs with phenotypic variability. <span><span class="ref-journal">Am J Med Genet Suppl. </span>1987;<span class="ref-vol">3</span>:233–41.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3130860" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3130860</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.ramsubir.2008.133">Ramsubir S, Nonaka T, Girbés CB, Carpentier S, Levade T, Medin JA. In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease. <span><span class="ref-journal">Mol Genet Metab. </span>2008;<span class="ref-vol">95</span>:133–41.</span> [<a href="/pmc/articles/PMC2614354/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2614354</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18805722" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18805722</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.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. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<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></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.rubboli.2015.692">Rubboli G, Veggiotti P, Pini A, Berardinelli A, Cantalupo G, Bertini E, Tiziano FD, D'Amico A, Piazza E, Abiusi E, Fiori S, Pasini E, Darra F, Gobbi G, Michelucci R. Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH1. <span><span class="ref-journal">Epilepsia. </span>2015;<span class="ref-vol">56</span>:692–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25847462" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25847462</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.samuelsson.1971.393">Samuelsson K, Zetterström R. Ceramides in a patient with lipogranulomatosis (Farber's disease) with chronic course. <span><span class="ref-journal">Scand J Clin Lab Invest. </span>1971;<span class="ref-vol">27</span>:393–405.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/5109101" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5109101</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.sathe.2013.s93">Sathe S, Pearson T. Phenotypic characterization of the spinal muscular atrophy with progressive myoclonus epilepsy syndrome caused by ASAH1 mutations. <span><span class="ref-journal">Mol Genet Metab. </span>2013;<span class="ref-vol">111</span>:S93.</span></div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.schmoeckel.1980.153">Schmoeckel C. Subtle clues to diagnosis of skin diseases by electron microscopy. "Farber bodies" in disseminated lipogranulomatosis (Farber's disease). <span><span class="ref-journal">Am J Dermatopathol. </span>1980;<span class="ref-vol">2</span>:153–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7246981" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7246981</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.schuchman.2014.s173">Schuchman E. Farber disease explains subset of juvenile idiopathic arthritis. <span><span class="ref-journal">Arthritis Rheumatol. </span>2014;<span class="ref-vol">66</span>:S173.</span></div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.shtraizent.2008.11253">Shtraizent N, Eliyahu E, Park JH, He X, Shalgi R, Schuchman EH. Autoproteolytic cleavage and activation of human acid ceramidase. <span><span class="ref-journal">J Biol Chem. </span>2008;<span class="ref-vol">283</span>:11253–9.</span> [<a href="/pmc/articles/PMC2431059/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2431059</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18281275" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18281275</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.stenson.2014.1">Stenson PD, Mort M, Ball EV, Shaw K, Phillips AD, Cooper DN. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. <span><span class="ref-journal">Hum Genet. </span>2014;<span class="ref-vol">133</span>:1.</span> [<a href="/pmc/articles/PMC3898141/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3898141</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24077912" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24077912</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.teoh.2016">Teoh HL, Solyom A, Schuchman EH, Mowat D, Roscioli T, Farrar M, Sampaio H. Polyarticular arthritis and spinal muscular atrophy in acid ceramidase deficiency. <span><span class="ref-journal">Pediatrics. </span>2016;<span class="ref-vol">138</span>(4)</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27650050" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27650050</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.topaloglu.2016.128">Topaloglu H, Melki J. Spinal muscular atrophy associated with progressive myoclonus epilepsy. <span><span class="ref-journal">Epileptic Disord. </span>2016;<span class="ref-vol">18</span>:128–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27647482" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27647482</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.torcoletti.2014.1533">Torcoletti M, Petaccia A, Pinto RM, Hladnik U, Locatelli F, Agostoni C, Corona F. Farber disease in infancy resembling juvenile idiopathic arthritis: identification of two new mutations and a good early response to allogeneic haematopoietic stem cell transplantation. <span><span class="ref-journal">Rheumatology (Oxford). </span>2014;<span class="ref-vol">53</span>:1533–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24614645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24614645</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.walia.2011.679">Walia JS, Neschadim A, Lopez-Perez O, Alayoubi A, Fan X, Carpentier S, Madden M, Lee CJ, Cheung F, Jaffray DA, Levade T, McCart JA, Medin JA. Autologous transplantation of lentivector/acid ceramidase-transduced hematopoietic cells in nonhuman primates. <span><span class="ref-journal">Hum Gene Ther. </span>2011;<span class="ref-vol">22</span>:679–87.</span> [<a href="/pmc/articles/PMC3155125/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3155125</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21280983" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21280983</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.yeager.2000.357">Yeager AM, Uhas KA, Coles CD, Davis PC, Krause WL, Moser HW. Bone marrow transplantation for infantile ceramidase deficiency (Farber disease). <span><span class="ref-journal">Bone Marrow Transplant. </span>2000;<span class="ref-vol">26</span>:357–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10967581" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10967581</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="asah1.REF.zhou.2012.5">Zhou J, Tawk M, Tiziano FD, Veillet J, Bayes M, Nolent F, Garcia V, Servidei S, Bertini E, Castro-Giner F, Renda Y, Carpentier S, Andrieu-Abadie N, Gut I, Levade T, Topaloglu H, Melki J. Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. <span><span class="ref-journal">Am J Hum Genet. </span>2012;<span class="ref-vol">91</span>:5–14.</span> [<a href="/pmc/articles/PMC3397266/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3397266</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22703880" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22703880</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK488189_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">David A Dyment</span>, DPhil, MD<div class="affiliation small">Children's Hospital of Eastern Ontario Research Institute<br />Department of Biochemistry, Microbiology, and Immunology<br />University of Ottawa<br />Ottawa, Ontario, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.no.oehc@tnemydd" class="oemail">ac.no.oehc@tnemydd</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Steffany AL Bennett</span>, PhD<div class="affiliation small">Department of Biochemistry, Microbiology, and Immunology<br />University of Ottawa<br />Ottawa, Ontario, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.awattou@ttenneb.nnaynaffets" class="oemail">ac.awattou@ttenneb.nnaynaffets</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jeffrey A Medin</span>, PhD<div class="affiliation small">Departments of Pediatrics and Biochemistry<br />Medical College of Wisconsin<br />Milwaukee, Wisconsin<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wcm@nidemj" class="oemail">ude.wcm@nidemj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Thierry Levade</span>, MD, PhD<div class="affiliation small">Laboratoire de Biochimie Métabolique<br />CHU Toulouse<br />INSERM U1037, Centre de Recherches en Cancérologie de Toulouse<br />Université Paul Sabatier<br />Toulouse, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="rf.mresni@edavel.yrreiht" class="oemail">rf.mresni@edavel.yrreiht</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">March 29, 2018</span>.</p><h3>Copyright</h3><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><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Dyment DA, Bennett SAL, Medin JA, et al. ASAH1-Related Disorders. 2018 Mar 29. 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></p></div><div class="small-screen-prev"><a href="/books/n/gene/arsacs/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/aspm-pm/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobasah1Tc"><div id="asah1.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ASAH1</i>-Related Disorders: Included Phenotypes</th></tr></thead><tbody><tr><td headers="hd_h_asah1.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Farber disease</div></li><li class="half_rhythm"><div>Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) <sup>1</sup></div></li><li class="half_rhythm"><div>Spinal muscular atrophy without epilepsy</div></li><li class="half_rhythm"><div>Progressive adult-onset brachydactyly due to osteolysis</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">For synonyms and outdated names see <a href="#asah1.Nomenclature">Nomenclature</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="asah1.TF.c.1"><p class="no_margin">For other genetic causes of this phenotype, see <a href="#asah1.Differential_Diagnosis">Differential Diagnosis</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Tmoleculargenetictestingusedi"><div id="asah1.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>ASAH1</i>-Related Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_2" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands by Phenotype with Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr><tr><th headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Farber disease</th><th headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SMA-PME</th></tr></thead><tbody><tr><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ASAH1</i>
|
|
</td><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_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_asah1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35/36</td><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/13</td></tr><tr><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></td><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/36 <sup>5</sup></td><td headers="hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_asah1.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/13 <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="asah1.TF.1.1"><p class="no_margin">See <a href="/books/NBK488189/?report=reader#asah1.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="asah1.TF.1.2"><p class="no_margin">See <a href="#asah1.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="asah1.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="asah1.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="asah1.TF.1.5"><p class="no_margin">One proband was a compound heterozygote for an intronic pathogenic variant (<a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus">c.917+4A>G</a>) and a deletion of exons 3-5 [<a class="bibr" href="#asah1.REF.alves.2013.276" rid="asah1.REF.alves.2013.276">Alves et al 2013</a>] (see <a href="#asah1.Molecular_Genetics">Molecular Genetics</a>, <b>Pathogenic variants</b>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="asah1.TF.1.6"><p class="no_margin">One proband was a compound heterozygote for the recurrent pathogenic variant (<a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobasah1Tasah1pathogenicvariantsdiscus">c.125C>T</a>) and a whole-gene deletion [<a class="bibr" href="#asah1.REF.zhou.2012.5" rid="asah1.REF.zhou.2012.5">Zhou et al 2012</a>] (see <a href="#asah1.Molecular_Genetics">Molecular Genetics</a>, <b>Pathogenic variants</b>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Tinheriteddisorderstoconsider"><div id="asah1.T.inherited_disorders_to_consider" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Inherited Disorders to Consider in the Differential Diagnosis of <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.inherited_disorders_to_consider/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.inherited_disorders_to_consider_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" style="text-align:left;vertical-align:middle;">Differential Disorder</th><th id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Differential Disorder</th></tr><tr><th headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4" id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping</th><th headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4" id="hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing</th></tr></thead><tbody><tr><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/sma/?report=reader">Spinal muscular atrophy</a> (SMA)</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SMN1</i>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lower MND w/onset age similar to <a href="/books/n/gene/sma/?report=reader">SMA III</a></td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Earlier onset of weakness in SMA I & II; no seizures or hearing loss in SMA</td></tr><tr><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/lafora/?report=reader">Progressive myoclonus epilepsy, Lafora type</a>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>EPM2</i>
|
|
<br />
|
|
<i>NHLRC1</i>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive myoclonic seizures</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No MND in Lafora disease</td></tr><tr><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/epm1/?report=reader">Unverricht-Lundborg disease</a>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CSTB</i>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive myoclonic jerks, tremor</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia & lack of MND in Unverricht-Lundborg disease</td></tr><tr><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/merrf/?report=reader">MERRF</a>
|
|
</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MT-TK</i> <sup>1</sup></td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mt</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myoclonic epilepsy, weakness, hearing loss</td><td headers="hd_h_asah1.T.inherited_disorders_to_consider_1_1_1_4 hd_h_asah1.T.inherited_disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia, optic atrophy, & characteristic muscle biopsy (ragged red fibers) in MERRF</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; MERRF = <i>m</i>yoclonic <i>e</i>pilepsy with <i>r</i>agged <i>r</i>ed <i>f</i>ibers; MND = motor neuron disease; MOI = mode of inheritance; mt = mitochondrial</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="asah1.TF.2.1"><p class="no_margin"><i>MT-TK</i>, a mitochondrial DNA gene, is the gene most commonly associated with MERRF. Pathogenic variants in <i>MT-TF, MT-TL1, MT-TI</i>, and <i>MT-TP</i> have also been described in a subset of individuals with MERRF.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Trecommendedevaluationsfollowin"><div id="asah1.T.recommended_evaluations_followin" class="table"><h3><span class="label">Table 3a. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis of an <i>ASAH1</i>-Related Disorder: Farber Disease</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.recommended_evaluations_followin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_asah1.T.recommended_evaluations_followin_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_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Constitutional</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for evidence of failure to thrive</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Airway & pulmonary assessment for evidence of ↓ pulmonary function due to granulomatous infiltrations</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of swallowing, feeding, & nutritional status, esp in later stages of disease</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to specialist in pediatric pain mgmt</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pain due to deforming joint contractures</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to rehab specialist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for functional disability in mobility & ADL.</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to pediatric neurologist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for evidence of lower motor neuron disease or seizure activity.</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hematologic</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for possible hematopoietic stem cell transplantation</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For those w/type 2 or 3 FD, as non-CNS symptoms may be improved</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Miscellaneous/</b>
|
|
<br />
|
|
<b>Other</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist or genetic counselor</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to palliative care specialist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">When deemed appropriate by family & care providers</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Trecommendedevaluationsfollowin1"><div id="asah1.T.recommended_evaluations_followin_1" class="table"><h3><span class="label">Table 3b. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis of an <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.recommended_evaluations_followin_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.recommended_evaluations_followin_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_asah1.T.recommended_evaluations_followin_1_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_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Constitutional</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for evidence of poor growth</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>ENT</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for sensorineural hearing loss.</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for pulmonary disease secondary to recurrent aspiration</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of feeding & nutritional status, esp in later stages of disease</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to rehab specialist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for functional disability in mobility & ADL.</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment for scoliosis</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to neurologist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To document extent of any weakness or other neurologic manifestations of SMA-PME & to evaluate for evidence of seizures</td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Miscellaneous/</b>
|
|
<br />
|
|
<b>Other</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist or genetic counselor</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to palliative care specialist</td><td headers="hd_h_asah1.T.recommended_evaluations_followin_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">When deemed appropriate by family & care providers</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Ttreatmentofmanifestationsini"><div id="asah1.T.treatment_of_manifestations_in_i" class="table"><h3><span class="label">Table 4a. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>ASAH1</i>-Related Disorder: Farber Disease</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.treatment_of_manifestations_in_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_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_asah1.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Aspiration pneumonia</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrostomy tube placement</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Compromised</b>
|
|
<br />
|
|
<b>airway</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tracheostomy</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider if airway compromised due to presence of granulomas or for those who are ventilator dependent</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Surgical removal of granulomas in airway & oral cavity</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In 1 case, surgical removal of granulomas resulted in improved oral intake & ↓ airway obstruction [<a class="bibr" href="#asah1.REF.haraoka.1997.405" rid="asah1.REF.haraoka.1997.405">Haraoka et al 1997</a>].</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Seizures</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard ASM as determined by treating neurologist</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cutaneous &</b>
|
|
<br />
|
|
<b>joint-related</b>
|
|
<br />
|
|
<b>symptoms of FD</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bone marrow transplantation (BMT)</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">BMT does not alter progression of motor neuron disease or other neurologic manifestations [<a class="bibr" href="#asah1.REF.yeager.2000.357" rid="asah1.REF.yeager.2000.357">Yeager et al 2000</a>, <a class="bibr" href="#asah1.REF.torcoletti.2014.1533" rid="asah1.REF.torcoletti.2014.1533">Torcoletti et al 2014</a>, <a class="bibr" href="#asah1.REF.cappellari.2016.149" rid="asah1.REF.cappellari.2016.149">Cappellari et al 2016</a>].</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hematopoietic stem cell transplantation</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Shown to improve only the peripheral manifestations of FD [<a class="bibr" href="#asah1.REF.ehlert.2007.15" rid="asah1.REF.ehlert.2007.15">Ehlert et al 2007</a>, <a class="bibr" href="#asah1.REF.jarisch.2014.1399" rid="asah1.REF.jarisch.2014.1399">Jarisch et al 2014</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Ttreatmentofmanifestationsini1"><div id="asah1.T.treatment_of_manifestations_in_i_1" class="table"><h3><span class="label">Table 4b. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>ASAH1</i>-Related Disorder: Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.treatment_of_manifestations_in_i_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.treatment_of_manifestations_in_i_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_asah1.T.treatment_of_manifestations_in_i_1_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_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing loss</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/n/gene/deafness-overview/?report=reader">Hereditary Hearing Loss and Deafness Overview</a>.</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Aspiration</b>
|
|
<br />
|
|
<b>pneumonia</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrostomy tube placement</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Scoliosis</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to orthopedist.</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Seizures</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard anti-seizure medication as determined by treating neurologist</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Improvement w/valproic acid observed in case reports, but ↓ in seizure frequency is temporary [<a class="bibr" href="#asah1.REF.dyment.2014.558" rid="asah1.REF.dyment.2014.558">Dyment et al 2014</a>, <a class="bibr" href="#asah1.REF.kernohan.2017.611" rid="asah1.REF.kernohan.2017.611">Kernohan et al 2017</a>]</td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Weakness</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT, OT, &/or physiatrist can assist w/use of orthotics, wheelchairs, or other assistive devices for mobility.</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Tremor</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard pharmacologic treatment for tremors to ↓ severity</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
<br />
|
|
<b>insufficiency</b>
|
|
</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Respiratory therapy; standard treatments for recurrent pneumonias</td><td headers="hd_h_asah1.T.treatment_of_manifestations_in_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider:
|
|
<ul><li class="half_rhythm"><div>Noninvasive ventilatory support (CPAP/BiPAP);</div></li><li class="half_rhythm"><div>Tracheostomy if ventilator dependent.</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapist; PT = physical therapist</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Trecommendedsurveillanceforind"><div id="asah1.T.recommended_surveillance_for_ind" class="table"><h3><span class="label">Table 5a. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>ASAH1</i>-Related Disorder: Farber Disease</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.recommended_surveillance_for_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency of Assessment / Comments</th></tr></thead><tbody><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Constitutional</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor growth for evidence of failure to thrive.</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At every visit, consider referral for feeding assessment if poor weight gain.</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Monitor general health & immunization status.</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_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_asah1.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of airway & for evidence of infiltrative pulmonary disease</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routinely</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of joints</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routinely</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Developmental</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor achievement of developmental milestones.</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Child psychologist or developmental pediatrician can assess for cognitive & behavioral issues. <sup>1</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="asah1.TF.5a.1"><p class="no_margin">Surveillance relevant to the milder forms of Farber disease (i.e., type 1 FD and type 2 FD)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1Trecommendedsurveillanceforind1"><div id="asah1.T.recommended_surveillance_for_ind_1" class="table"><h3><span class="label">Table 5b. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>ASAH1</i>-Related Disorder: SMA-PME</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.recommended_surveillance_for_ind_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.recommended_surveillance_for_ind_1_lrgtbl__"><table><thead><tr><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">System/Concern</th><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evaluation</th><th id="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Frequency/Comments</th></tr></thead><tbody><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Constitutional</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor growth w/emphasis on feeding & nutritional status.</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Monitor general health & immunization status.</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>ENT</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pulmonary function tests</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routinely</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for development of scoliosis.</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate disease progression (extent of lower motor neuron disease; status of seizure control).</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routinely</td></tr><tr><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Miscellaneous / Other</b>
|
|
</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for functional capacity & equipment needs (mobility, communication).</td><td headers="hd_h_asah1.T.recommended_surveillance_for_ind_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobasah1molgenTA"><div id="asah1.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>ASAH1-Related Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_asah1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_asah1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_asah1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_asah1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_asah1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_asah1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_asah1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/427" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ASAH1</i>
|
|
</a>
|
|
</td><td headers="hd_b_asah1.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=427" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">8p22</a>
|
|
</td><td headers="hd_b_asah1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q13510" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Acid ceramidase</a>
|
|
</td><td headers="hd_b_asah1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ASAH1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ASAH1 database</a>
|
|
</td><td headers="hd_b_asah1.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=ASAH1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ASAH1</a>
|
|
</td><td headers="hd_b_asah1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ASAH1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ASAH1</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="asah1.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus 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/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobasah1molgenTB"><div id="asah1.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for ASAH1-Related Disorders (<a href="/omim/159950,228000,613468" 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/NBK488189/table/asah1.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/159950" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">159950</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY; SMAPME</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/228000" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">228000</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">FARBER LIPOGRANULOMATOSIS; FRBRL</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613468" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613468</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N-ACYLSPHINGOSINE AMIDOHYDROLASE 1; ASAH1</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobasah1Tasah1pathogenicvariantsdiscus"><div id="asah1.T.asah1_pathogenic_variants_discus" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>ASAH1</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK488189/table/asah1.T.asah1_pathogenic_variants_discus/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__asah1.T.asah1_pathogenic_variants_discus_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.125C>T</td><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Thr42Met</td><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_177924.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_177924<wbr style="display:inline-block"></wbr>​.5</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_808592.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_808592<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td></tr><tr><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.703G>C</td><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly235Arg</td></tr><tr><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.917+4A>G <sup>1</sup></td><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_asah1.T.asah1_pathogenic_variants_discus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_177924.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_177924<wbr style="display:inline-block"></wbr>​.5</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><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></dl><dl class="bkr_refwrap"><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/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="asah1.TF.6.1"><p class="no_margin">
|
|
<a href="https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs397509415" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs397509415</a>
|
|
</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.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></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal107 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/3968615.js" snapshot="books"></script></body>
|
|
</html>
|