184 lines
115 KiB
Text
184 lines
115 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="NBK1321">
|
|
<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="/NBK1321/?report=reader">
|
|
<meta name="ncbi_pagename" content="X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY - GeneReviews® - NCBI Bookshelf"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>X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY - GeneReviews® - NCBI Bookshelf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/x-scid/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/sedt/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="NOINDEX,NOFOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2014/04/03">
|
|
<meta name="citation_author" content="Soumeya Bekri">
|
|
<meta name="citation_author" content="Marc D'Hooghe">
|
|
<meta name="citation_author" content="Pieter Vermeersch">
|
|
<meta name="citation_pmid" content="20301496">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1321/">
|
|
<meta name="citation_keywords" content="ATP-binding cassette sub-family B member 7, mitochondrial">
|
|
<meta name="citation_keywords" content="ABCB7">
|
|
<meta name="citation_keywords" content="X-Linked Sideroblastic Anemia and Ataxia">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="Soumeya Bekri">
|
|
<meta name="DC.Contributor" content="Marc D'Hooghe">
|
|
<meta name="DC.Contributor" content="Pieter Vermeersch">
|
|
<meta name="DC.Date" content="2014/04/03">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1321/">
|
|
<meta name="description" content="NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.">
|
|
<meta name="og:title" content="X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1321/">
|
|
<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="warning" content="This publication is provided for historical reference only and the information may be out of date.">
|
|
<meta name="bk-non-canon-loc" content="/books/n/gene/sider-anemia/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1321/">
|
|
<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">.main-content {background:transparent repeat-y top left;background-image:url(/corehtml/pmc/css/bookshelf/2.26/img/archive.png);background-size: auto, contain; padding:0 0 0 3em }</style>
|
|
<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="CE8DBE2F7D5982E10000000001370106.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/NBK1321/?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/x-scid/?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">X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/sedt/?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/NBK1321/"><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/NBK1321/&text=X-Linked%20Sideroblastic%20Anemia%20and%20Ataxia%20%02013%20RETIRED%20CHAPTER%2C%20FOR%20HISTORICAL%20REFERENCE%20ONLY"><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/NBK1321/?report=classic">Switch to classic view</a><a href="/books/NBK1321/pdf/Bookshelf_NBK1321.pdf">PDF (702K)</a><a href="/books/NBK1321/?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%20NBK1321%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8DBE2F7D5982E10000000001370106.4">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"><p class="vip-notice retraction"><strong>This publication is provided for historical reference only and the information may be out of date.</strong></p><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="_NBK1321_"><span class="title" itemprop="name">X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY</span></h1><p class="contribs">Bekri S, D'Hooghe M, Vermeersch P.</p><p class="fm-aai"><a href="#_NBK1321_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 19 minutes</em></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="sider-anemia.Summary" itemprop="description"><h2 id="_sider-anemia_Summary_">Summary</h2><p>
|
|
<b>NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.</b>
|
|
</p><div><h4 class="inline">Clinical characteristics.</h4><p>X-linked sideroblastic anemia and ataxia (XLSA/A) is characterized by moderate anemia and early-onset spinocerebellar syndrome in males, manifest primarily as delayed walking, ataxia evident in early childhood, dysmetria, and dysdiadochokinesis. When present the intention tremor is mild and the dysarthria is mild to moderately severe. The ataxia has been described to be either non-progressive or slowly progressive. Upper motor neuron (UMN) signs in the legs, manifest by brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses, are present in some males. Need for crutches or a wheelchair has been reported. Strabismus is seen in some males. Nystagmus and hypometric saccades may occur. Mild learning disability and depression are seen. The moderate hypochromic and microcytic anemia does not cause symptoms. Carrier (heterozygous) females have a normal neurologic examination and may show mild hematologic abnormalities.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of XLSA/A is suspected in males with characteristic neurologic findings and the presence of moderate hypochromic and microcytic anemia, elevated whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP), and ring sideroblasts on bone marrow examination. Pappenheimer bodies are seen in peripheral blood smear. The diagnosis is confirmed in a male by identification of a hemizygous pathogenic variant in <i>ABCB7.</i></p><p>Females have a normal neurologic examination and may have a dimorphic blood smear with both hypochromic microcytic red blood cells and normal red blood cells; they may have ring sideroblasts on bone marrow examination.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Males with XLSA/A benefit from early physical therapy to facilitate acquisition of gross motor skills. Adaptive devices such as ankle fixation orthoses and walkers may be needed. Weighted eating utensils may help promote independent skills in childhood. Speech therapy may improve intelligibility problems from dysarthria. Difficulty with handwriting may be managed with computers for word processing.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>XLSA/A is inherited in an X-linked manner. Heterozygous females have a 50% chance of transmitting the pathogenic variant in each pregnancy. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be affected. Males with XLSA/A will pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing of at-risk female relatives and prenatal testing for a pregnancy at increased risk are possible if the <i>ABCB7</i> pathogenic variant in the family is known.</p></div></div><div id="sider-anemia.Diagnosis"><h2 id="_sider-anemia_Diagnosis_">Diagnosis</h2><p><b>Males</b> with X-linked sideroblastic anemia and ataxia (XLSA/A) exhibit the following signs:</p><ul><li class="half_rhythm"><div>Ataxia and incoordination. Note: <a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al [1985]</a> described non-progressive ataxia; <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al [2001]</a> described ataxia that was possibly slowly progressive.</div></li><li class="half_rhythm"><div>Upper motor neuron (UMN) signs (i.e., brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses) in the legs (present in some males)</div></li><li class="half_rhythm"><div>Mild asymptomatic hypochromic, microcytic anemia</div><ul><li class="half_rhythm"><div class="half_rhythm">Hematocrit ranges from 26% to 35%.</div></li><li class="half_rhythm"><div class="half_rhythm">Mean corpuscular volume (MCV fl) is low (<a href="/books/NBK1321/table/sider-anemia.T.mean_corpuscular_volume_m/?report=objectonly" target="object" rid-ob="figobsideranemiaTmeancorpuscularvolumem">Table 1</a>).</div></li><li class="half_rhythm"><div class="half_rhythm">Peripheral blood smears show in affected males: (1) microcytic and hypochromic red cells with marked poikilocytosis, reticulocytosis, and heavy stippling; (2) Pappenheimer bodies (iron inclusions in more mature erythrocytes). These siderocytes are present in the peripheral blood of affected males and in some heterozygous females.</div></li><li class="half_rhythm"><div class="half_rhythm">Bone marrow examination shows increased iron stores with ring sideroblasts (<a class="figpopup" href="/books/NBK1321/figure/sider-anemia.F1/?report=objectonly" target="object" rid-figpopup="figsideranemiaF1" rid-ob="figobsideranemiaF1">Figure 1</a>). Note: Serum iron parameters are normal.</div></li><li class="half_rhythm"><div class="half_rhythm">High levels of whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP) further support the diagnosis [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>, <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>, <a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al 2001</a>, <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al 2012</a>].</div><div class="half_rhythm">Note: (1) Whole blood TEP may be used as a screening tool [<a class="bibr" href="#sider-anemia.REF.piomelli.1975.1519" rid="sider-anemia.REF.piomelli.1975.1519">Piomelli et al 1975</a>, <a class="bibr" href="#sider-anemia.REF.hart.1981.220" rid="sider-anemia.REF.hart.1981.220">Hart & Piomelli 1981</a>]. (2) If no <i>ABCB7</i> pathogenic variant is identified (see <b>The diagnosis of XLSA/A</b> below), the presence of characteristic bone marrow changes and high levels of TEP identified in at least one affected family member with a family history consistent with X-linked inheritance strongly suggests the diagnosis of XLSA/A.</div></li></ul></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figsideranemiaF1" co-legend-rid="figlgndsideranemiaF1"><a href="/books/NBK1321/figure/sider-anemia.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figsideranemiaF1" rid-ob="figobsideranemiaF1"><img class="small-thumb" src="/books/NBK1321/bin/sider-anemia-Image001.gif" src-large="/books/NBK1321/bin/sider-anemia-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndsideranemiaF1"><h4 id="sider-anemia.F1"><a href="/books/NBK1321/figure/sider-anemia.F1/?report=objectonly" target="object" rid-ob="figobsideranemiaF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Ringed sideroblast Prussian blue staining of the bone marrow aspirate (x1000) showing a normal erythroid precursor (straight arrow) and a ringed sideroblast containing many iron granules around the nucleus (curved arrow).</p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsideranemiaTmeancorpuscularvolumem"><a href="/books/NBK1321/table/sider-anemia.T.mean_corpuscular_volume_m/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobsideranemiaTmeancorpuscularvolumem"><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="sider-anemia.T.mean_corpuscular_volume_m"><a href="/books/NBK1321/table/sider-anemia.T.mean_corpuscular_volume_m/?report=objectonly" target="object" rid-ob="figobsideranemiaTmeancorpuscularvolumem">Table 1. </a></h4><p class="float-caption no_bottom_margin">Mean Corpuscular Volume (MCV fl) in XLSA/A </p></div></div><p><b>Heterozygous females</b> have a normal neurologic examination and may show mild hematologic abnormalities, including Pappenheimer bodies in peripheral blood smear [<a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>] and ringed sideroblasts in bone marrow aspirate [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>]. Some heterozygous females also have increased levels of whole blood TEP and ZnEP [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>].</p><p><b>The diagnosis of XLSA/A</b> is confirmed in a male by presence of a hemizygous pathogenic variant in <i>ABCB7.</i></p><ul><li class="half_rhythm"><div class="half_rhythm"><b>One genetic testing strategy</b> is molecular genetic testing of <i>ABCB7,</i> the only gene in which pathogenic variants are known to cause XLSA/A. Sequence analysis should be performed first; if no pathogenic variant is identified, deletion/duplication analysis may be considered.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>An alternative genetic testing strategy</b> is use of a multigene panel that includes <i>ABCB7</i> and other genes of interest (see <a href="#sider-anemia.Differential_Diagnosis">Differential Diagnosis</a>). Note: The genes included and the methods used in multigene panels vary by laboratory and over time.</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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsideranemiaTmoleculargenetictesting"><a href="/books/NBK1321/table/sider-anemia.T.molecular_genetic_testing/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobsideranemiaTmoleculargenetictesting"><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="sider-anemia.T.molecular_genetic_testing"><a href="/books/NBK1321/table/sider-anemia.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobsideranemiaTmoleculargenetictesting">Table 2. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in X-Linked Sideroblastic Anemia and Ataxia </p></div></div></div><div id="sider-anemia.Clinical_Characteristics"><h2 id="_sider-anemia_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sider-anemia.Clinical_Description"><h3>Clinical Description</h3><p>To date, four unrelated families with X-linked sideroblastic anemia and ataxia (XLSA/A) have been reported [<a class="bibr" href="#sider-anemia.REF.allikmets.1999.743" rid="sider-anemia.REF.allikmets.1999.743">Allikmets et al 1999</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>, <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>, <a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al 2001</a>, <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al 2012</a>].</p><p><a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al [1985]</a> reported two families with a non-progressive spinocerebellar syndrome and sideroblastic anemia, both segregating in an X-linked recessive mode of inheritance. Four males in two generations and a fifth male from an unrelated family were affected. <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al [2000]</a> reported two affected brothers with XLSA/A. <a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al [2001]</a> reported another family with two affected brothers and two affected maternal uncles. <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al [2012]</a> reported a boy with XLSA/A.</p><p><b>Ataxia/neurologic findings.</b> Males have an early-onset spinocerebellar syndrome manifesting primarily as delayed walking, ataxia evident from early childhood, dysmetria, and dysdiadochokinesis. When present, intention tremor is mild and dysarthria is mild to moderately severe.</p><p>In some, but not all, affected members of one family, the ataxia appeared to improve with time, such that truncal titubation decreased and walking became progressively easier [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>]. However, in older patients slow deterioration of walking can be seen in the fifth or sixth decade [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>, <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>].</p><p>Need for crutches and/or a wheel chair have been reported.</p><p>Upper motor neuron (UMN) signs in the legs, manifest by brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses are present in some males.</p><p>Strabismus is seen in some males. Extraocular movements are normal; however, nystagmus and hypometric saccades may occur.</p><p>Intellectual abilities are generally within the normal range. Mild learning disability and depression have been seen [Pagon & Bird, personal communication] and one person was reported to have "schizophrenia" [<a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>].</p><p>Pes cavus, scoliosis, and muscle wasting are not present.</p><p>Impairment of visual acuity either from optic atrophy or retinal dystrophy is not seen.</p><p>In most cases brain MRI shows cerebellar atrophy/hypoplasia [<a class="bibr" href="#sider-anemia.REF.raskind.1991.335" rid="sider-anemia.REF.raskind.1991.335">Raskind et al 1991</a>].</p><p><b>Anemia.</b> The anemia is mild and does not cause symptoms.</p><p><b>Iron storage.</b> Despite the finding of increased iron stores and ring sideroblasts on bone marrow examination, systemic iron overload has not been described. Serum iron studies including serum concentration of iron, total iron binding capacity (TIBC), per cent TIBC saturation, and serum concentration of ferritin were normal in the families reported by <a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al [1985]</a> and <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al [2001]</a>.</p><p><b>Heterozygotes.</b> Carrier females have a normal neurologic examination.</p></div><div id="sider-anemia.GenotypePhenotype_Correlati"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations are known.</p></div><div id="sider-anemia.Prevalence"><h3>Prevalence</h3><p>Four families and one male who was a simplex case (i.e., a single occurrence in a family) have been reported to date [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>, <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al 2001</a>, <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al 2012</a>]. The prevalence of the disorder is probably underestimated because of failure to recognize the mild anemia in males with the characteristic ataxia.</p></div></div><div id="sider-anemia.Genetically_Related_Allelic"><h2 id="_sider-anemia_Genetically_Related_Allelic_">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>ABCB7</i>.</p><p>In investigations of individuals with refractory anemia with ring sideroblasts (RARS), an acquired myelodysplastic syndrome (MDS) characterized by excess iron accumulation in the mitochondria of erythroblasts, <a class="bibr" href="#sider-anemia.REF.boultwood.2008.e1970" rid="sider-anemia.REF.boultwood.2008.e1970">Boultwood et al [2008]</a> identified a strong relationship between an increasing percentage of bone marrow ring sideroblasts and decreasing <i>ABCB7</i> expression levels, suggesting that <i>ABCB7</i> is a candidate gene for RARS. Pathogenic variants in <i>SF3B1</i>, a component of the RNA splicing machinery, were associated with a majority of RARS [<a class="bibr" href="#sider-anemia.REF.yoshida.2011.64" rid="sider-anemia.REF.yoshida.2011.64">Yoshida et al 2011</a>]. <a class="bibr" href="#sider-anemia.REF.nikpour.2013.889" rid="sider-anemia.REF.nikpour.2013.889">Nikpour et al [2013]</a> showed that <i>ABCB7</i> expression is downregulated when <i>SF3B1</i> is mutated. Moreover, ABCB7 downregulation reduces erythroid differentiation, growth, and colony formation of K562 cells [<a class="bibr" href="#sider-anemia.REF.nikpour.2013.889" rid="sider-anemia.REF.nikpour.2013.889">Nikpour et al 2013</a>].</p></div><div id="sider-anemia.Differential_Diagnosis"><h2 id="_sider-anemia_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Sideroblastic anemia.</b> The sideroblastic anemias are a heterogeneous group of acquired and heritable anemias characterized by ringed sideroblasts (erythroid precursors - present in the bone marrow - that have pathologic iron overload in the mitochondria); the perinuclear location of mitochondria leads to the characteristic ringed appearance [<a class="bibr" href="#sider-anemia.REF.camaschella.2008.27" rid="sider-anemia.REF.camaschella.2008.27">Camaschella 2008</a>, <a class="bibr" href="#sider-anemia.REF.bergmann.2010.273" rid="sider-anemia.REF.bergmann.2010.273">Bergmann et al 2010</a>]. Iron inclusions, called Pappenheimer bodies, may also be observed in more mature erythrocytes [<a class="bibr" href="#sider-anemia.REF.sears.2004.249" rid="sider-anemia.REF.sears.2004.249">Sears & Udden 2004</a>, <a class="bibr" href="#sider-anemia.REF.camaschella.2008.27" rid="sider-anemia.REF.camaschella.2008.27">Camaschella 2008</a>] (<a class="figpopup" href="/books/NBK1321/figure/sider-anemia.F1/?report=objectonly" target="object" rid-figpopup="figsideranemiaF1" rid-ob="figobsideranemiaF1">Figure 1</a>).</p><p>The most common congenital sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutation of <i>ALAS2</i>. XLSA is characterized by hepatic and systemic iron overload but not ataxia (as expression of <i>ALAS2</i> is confined to erythroid tissues) [<a class="bibr" href="#sider-anemia.REF.napier.2005.1867" rid="sider-anemia.REF.napier.2005.1867">Napier et al 2005</a>].</p><p>Other causes of congenital sideroblastic anemia include mutation of genes that encode proteins affecting mitochondrial metabolism [<a class="bibr" href="#sider-anemia.REF.bergmann.2010.273" rid="sider-anemia.REF.bergmann.2010.273">Bergmann et al 2010</a>, <a class="bibr" href="#sider-anemia.REF.fujiwara.2013.675" rid="sider-anemia.REF.fujiwara.2013.675">Fujiwara & Harigae 2013</a>] and/or affect iron-sulfur (Fe-S) cluster protein biosynthesis, assembly, or function. Fe-S proteins, which are essential for fundamental metabolic processes such as respiration and gene expression, are synthesized in the mitochondria and are either associated with mitochondrial apoprotein to form mitochondrial Fe/S proteins or exported to the cytosol (via the ABCB7 transporter) to assist in the formation of cytosolic and nuclear Fe-S proteins [<a class="bibr" href="#sider-anemia.REF.sheftel.2010.302" rid="sider-anemia.REF.sheftel.2010.302">Sheftel et al 2010</a>]. These genes include the following:</p><ul><li class="half_rhythm"><div><i>SLC25A38</i> (encoding an erythroid specific mitochondrial transporter) [<a class="bibr" href="#sider-anemia.REF.guernsey.2009.651" rid="sider-anemia.REF.guernsey.2009.651">Guernsey et al 2009</a>]</div></li><li class="half_rhythm"><div><i>SLC19A2</i> (encoding a high-affinity thiamine transporter)</div></li><li class="half_rhythm"><div><i>PUS1</i> (RNA-modifying enzyme pseudouridine synthase 1) [<a class="bibr" href="#sider-anemia.REF.bykhovskaya.2004.1303" rid="sider-anemia.REF.bykhovskaya.2004.1303">Bykhovskaya et al 2004</a>]</div></li><li class="half_rhythm"><div><i>ABCB7</i> (encoding mitochondrial ATP-binding cassette transporter), the cause of XLSA/A</div></li><li class="half_rhythm"><div><i>GLRX5</i> (encoding monothiol glutaredoxin 5) [<a class="bibr" href="#sider-anemia.REF.camaschella.2007.1353" rid="sider-anemia.REF.camaschella.2007.1353">Camaschella et al 2007</a>], associated with a Fe-S cluster biosynthetic defect (the assembly of mitochondrial Fe/S proteins). The deregulation of mitochondrial iron metabolism results in sideroblastic anemia.</div></li><li class="half_rhythm"><div><i>YARS2</i> (mitochondrial tyrosyl-tRNA synthase) [<a class="bibr" href="#sider-anemia.REF.riley.2010.52" rid="sider-anemia.REF.riley.2010.52">Riley et al 2010</a>]</div></li><li class="half_rhythm"><div>Mitochondrial DNA deletions, duplications and rearrangements (Pearson marrow-pancreas syndrome) [<a class="bibr" href="#sider-anemia.REF.fleming.2002.270" rid="sider-anemia.REF.fleming.2002.270">Fleming 2002</a>]</div></li></ul><p>Another ataxia linked to Fe-S cluster protein is <a href="/books/n/gene/friedreich/?report=reader">Friedreich ataxia</a> (FRDA), caused by mutation of <i>FXN</i>, which encodes the mitochondrial protein frataxin whose main role is to supply iron in a bioavailable form for mitochondrial Fe-S cluster synthesis (<a class="figpopup" href="/books/NBK1321/figure/sider-anemia.F2/?report=objectonly" target="object" rid-figpopup="figsideranemiaF2" rid-ob="figobsideranemiaF2">Figure 2</a>) [<a class="bibr" href="#sider-anemia.REF.ye.2010b.4945" rid="sider-anemia.REF.ye.2010b.4945">Ye & Rouault 2010b</a>]. In persons with FRDA excess iron accumulation is observed in mitochondria of cardiac myocytes and neurons [<a class="bibr" href="#sider-anemia.REF.rouault.2008.398" rid="sider-anemia.REF.rouault.2008.398">Rouault & Tong 2008</a>, <a class="bibr" href="#sider-anemia.REF.ye.2010b.4945" rid="sider-anemia.REF.ye.2010b.4945">Ye & Rouault 2010b</a>]; however, persons with FRDA do not demonstrate significant anemia, suggesting either that frataxin is not essential for heme synthesis and erythropoiesis or that frataxin deficiency does not compromise erythropoietic tissues [<a class="bibr" href="#sider-anemia.REF.stemmler.2010.26737" rid="sider-anemia.REF.stemmler.2010.26737">Stemmler et al 2010</a>, <a class="bibr" href="#sider-anemia.REF.ye.a" rid="sider-anemia.REF.ye.a">Ye & Rouault 2010a</a>].</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figsideranemiaF2" co-legend-rid="figlgndsideranemiaF2"><a href="/books/NBK1321/figure/sider-anemia.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figsideranemiaF2" rid-ob="figobsideranemiaF2"><img class="small-thumb" src="/books/NBK1321/bin/sider-anemia-Image002.gif" src-large="/books/NBK1321/bin/sider-anemia-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndsideranemiaF2"><h4 id="sider-anemia.F2"><a href="/books/NBK1321/figure/sider-anemia.F2/?report=objectonly" target="object" rid-ob="figobsideranemiaF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Fe-S cluster biogenesis, heme synthesis and hypothetic effects of defects in ABCB7 Adapted from D'Hooghe et al [2012] with permission</p></div></div><p>Of note, in murine cultured fibroblasts with decreased levels of frataxin, some Fe-S cluster proteins are deficient, iron accumulates in mitochondria, and oxidant sensitivity is observed as in the human disease [<a class="bibr" href="#sider-anemia.REF.calmels.2009.e6379" rid="sider-anemia.REF.calmels.2009.e6379">Calmels et al 2009</a>]. The causal links among these effects are not well defined [<a class="bibr" href="#sider-anemia.REF.stemmler.2010.26737" rid="sider-anemia.REF.stemmler.2010.26737">Stemmler et al 2010</a>].</p><p><b>Ataxia.</b> The diagnostic approach to the numerous heritable ataxias can be quite challenging. Some hereditary ataxias typically present before age three years, including <a href="/books/n/gene/ataxia-telangiectas/?report=reader">ataxia-telangiectasia</a>, <a href="/books/n/gene/sca-io/?report=reader">infantile-onset spinocerebellar ataxia</a>, X-linked sideroblastic anemia with ataxia (XLSA/A), <a href="/books/n/gene/cdg/?report=reader">congenital disorders of glycosylation</a>, and cerebellar malformations (e.g., Dandy-Walker malformation) [<a class="bibr" href="#sider-anemia.REF.bernard.2008.194" rid="sider-anemia.REF.bernard.2008.194">Bernard & Shevell 2008</a>].</p><p>X-linked spinocerebellar ataxia has been reported, but is rare (see <a href="/books/n/gene/ataxias/?report=reader">Hereditary Ataxia Overview</a>). None has been associated with anemia. Mutation of <i>ABCB7</i> should be considered in any unexplained X-linked spinocerebellar ataxia, even in the absence of clear hematologic changes.</p></div><div id="sider-anemia.Management"><h2 id="_sider-anemia_Management_">Management</h2><div id="sider-anemia.Evaluations_Following_Initi"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease in an individual diagnosed with sideroblastic anemia and ataxia (XLSA/A), the following evaluations are recommended:</p><ul><li class="half_rhythm"><div>Neurologic examination</div></li><li class="half_rhythm"><div>Brain CT or MRI</div></li><li class="half_rhythm"><div>Psychological testing if indicated</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor</div></li></ul></div><div id="sider-anemia.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>There is no effective treatment for XLSA/A.</p><p>Males with ataxia benefit from early physical therapy to facilitate acquisition of gross motor skills. Adaptive devices such as ankle fixation orthoses and walkers may be needed.</p><p>Weighted eating utensils may help promote independent skills in childhood.</p><p>Speech therapy may improve intelligibility problems resulting from dysarthria.</p><p>Difficulty with handwriting may be managed with computers for word processing.</p><p>The anemia is usually mild and asymptomatic and does not require treatment; hepatic and systemic iron overload does not occur.</p></div><div id="sider-anemia.Surveillance"><h3>Surveillance</h3><p>It is debated whether monitoring for possible iron overload is warranted in older individuals through routine screening of serum iron concentration, total iron binding capacity (TIBC), and serum ferritin concentration; iron overload is theoretically possible but has not been reported.</p></div><div id="sider-anemia.Evaluation_of_Relatives_at"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#sider-anemia.Related_Genetic_Counseling">Related Genetic Counseling Issues</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="sider-anemia.Therapies_Under_Investigati"><h3>Therapies Under Investigation</h3><p>One possible therapeutic approach to some of the disorders involving iron misdistribution is drug-mediated iron relocation. Deferiprone (DFP), an iron chelator used to treat iron overload, has iron-relocating abilities when used to treat disorders of regional iron accumulation. Because of their possible side effects, siderophores (small, high-affinity iron chelating compounds secreted by microorganisms) and other chelators must be administered with care; thus, the potential use of iron-redistributing agents in some iron-misdistribution diseases (such as XLSA/A) warrants rigorous investigation [<a class="bibr" href="#sider-anemia.REF.boddaert.2007.401" rid="sider-anemia.REF.boddaert.2007.401">Boddaert et al 2007</a>, <a class="bibr" href="#sider-anemia.REF.camaschella.2008.27" rid="sider-anemia.REF.camaschella.2008.27">Camaschella 2008</a>, <a class="bibr" href="#sider-anemia.REF.kakhlon.2010.187" rid="sider-anemia.REF.kakhlon.2010.187">Kakhlon et al 2010</a>].</p><p>Search <a href="http://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="http://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="sider-anemia.Genetic_Counseling"><h2 id="_sider-anemia_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="sider-anemia.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>X-linked sideroblastic anemia and ataxia (XLSA/A) is inherited in an X-linked manner.</p></div><div id="sider-anemia.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disease nor will he be a carrier of the pathogenic <i>ABCB7</i> allelic variant.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is an obligate carrier.</div></li><li class="half_rhythm"><div>If pedigree analysis reveals that a male proband is the only affected family member, his mother may be a carrier or the pathogenic variant may be <i>de novo</i> in him (in which case the mother is not a carrier).</div></li><li class="half_rhythm"><div>If a woman has more than one affected son and the pathogenic variant cannot be detected in her DNA, she has germline mosaicism. To date germline mosaicism has not been reported in XLSA/A.</div></li></ul><p>
|
|
<b>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The risk to sibs depends on the carrier status of the mother.</div></li><li class="half_rhythm"><div>If the mother of the proband is a carrier, the chance of transmitting the pathogenic variant in each pregnancy is 50%. Male sibs who inherit the pathogenic <i>ABCB7</i> variant will be affected; female sibs who inherit the pathogenic variant will be carriers and will not be affected.</div></li><li class="half_rhythm"><div>If the pathogenic variant cannot be detected in the DNA of the mother of the only affected male in the family, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Males with XLSA/A will pass the pathogenic variant to all of their daughters and none of their sons.</p><p><b>Other family members.</b> The proband's maternal aunts may be at risk of being carriers and the aunt's offspring, depending on their gender, may be at risk of being carriers or of being affected.</p></div><div id="sider-anemia.Heterozygote_Carrier_Detect"><h3>Heterozygote (Carrier) Detection</h3><p>Heterozygous females (carriers) are asymptomatic.</p><ul><li class="half_rhythm"><div>They have a normal neurologic examination with no cerebellar dysfunction.</div></li><li class="half_rhythm"><div>They have a normal hematocrit, but may have a dimorphic blood smear with hypochromic microcytic red blood cells and normal red blood cells, sideroblasts on bone marrow examination. Some also have increased levels of whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP) [<a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al 1985</a>, <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al 2012</a>].</div></li></ul><p>Carrier testing of at-risk female relatives is possible if the pathogenic variant has been identified in the family.</p></div><div id="sider-anemia.Related_Genetic_Counseling"><h3>Related Genetic Counseling Issues</h3><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, 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 affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking</b> is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.</p></div><div id="sider-anemia.Prenatal_Testing_and_Preimp"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ABCB7</i> pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk 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, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. 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="sider-anemia.Resources"><h2 id="_sider-anemia_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>euro-ATAXIA (European Federation of Hereditary Ataxias)</b>
|
|
</div><div>Ataxia UK</div><div>Lincoln House, Kennington Park, 1-3 Brixton Road</div><div>London SW9 6DE</div><div>United Kingdom</div><div><b>Phone:</b> +44 (0) 207 582 1444</div><div><b>Email:</b> smillman@ataxia.org.uk</div><div>
|
|
<a href="https://www.euroataxia.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.euroataxia.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Medline Plus</b>
|
|
</div><div>
|
|
<a href="http://www.nlm.nih.gov/medlineplus/bonemarrowdiseases.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Bone Marrow Diseases</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>National Ataxia Foundation</b>
|
|
</div><div>2600 Fernbrook Lane</div><div>Suite 119</div><div>Minneapolis MN 55447</div><div><b>Phone:</b> 763-553-0020</div><div><b>Email:</b> naf@ataxia.org</div><div>
|
|
<a href="http://www.ataxia.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ataxia.org</a>
|
|
</div></li></ul>
|
|
</div><div id="sider-anemia.Molecular_Genetics"><h2 id="_sider-anemia_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="figsideranemiamolgenTA"><a href="/books/NBK1321/table/sider-anemia.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobsideranemiamolgenTA"><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="sider-anemia.molgen.TA"><a href="/books/NBK1321/table/sider-anemia.molgen.TA/?report=objectonly" target="object" rid-ob="figobsideranemiamolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">X-Linked Sideroblastic Anemia and Ataxia: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsideranemiamolgenTB"><a href="/books/NBK1321/table/sider-anemia.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobsideranemiamolgenTB"><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="sider-anemia.molgen.TB"><a href="/books/NBK1321/table/sider-anemia.molgen.TB/?report=objectonly" target="object" rid-ob="figobsideranemiamolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for X-Linked Sideroblastic Anemia and Ataxia (View All in OMIM) </p></div></div><div id="sider-anemia.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ABCB7</i> encodes a mitochondrial adenosine triphosphate (ATP)-binding cassette (ABC) transporter protein involved in iron homeostasis. The family of ABC transporters consists of a large group of ATP-dependent transmembrane proteins that specifically transport a wide variety of substrates across cell and organelle membranes [<a class="bibr" href="#sider-anemia.REF.holland.2011.1" rid="sider-anemia.REF.holland.2011.1">Holland 2011</a>, <a class="bibr" href="#sider-anemia.REF.moitra.2011.29" rid="sider-anemia.REF.moitra.2011.29">Moitra & Dean 2011</a>]. The human genome contains 49 ABC genes. Compared to bacteria, human mitochondria surprisingly harbor a very small number (≤4) of ABC transporters [<a class="bibr" href="#sider-anemia.REF.burke.2007.73" rid="sider-anemia.REF.burke.2007.73">Burke & Ardehali 2007</a>, <a class="bibr" href="#sider-anemia.REF.zutz.2009.681" rid="sider-anemia.REF.zutz.2009.681">Zutz et al 2009</a>]. Mitochondrial ABC transporters belong to the subfamily B and assemble as homodimers of half-transporters [<a class="bibr" href="#sider-anemia.REF.zutz.2009.681" rid="sider-anemia.REF.zutz.2009.681">Zutz et al 2009</a>]. ABCB7 is found in the inner mitochondrial membrane.</p><p>The substrate transported by the ABCB7 transporter is not fully characterized. Initially, ABCB7 was thought to be involved in transport of heme from the mitochondria to the cytosol [<a class="bibr" href="#sider-anemia.REF.shimada.1998.115" rid="sider-anemia.REF.shimada.1998.115">Shimada et al 1998</a>]. Recent studies in different species suggest relationships between heme biosynthetic pathways, iron-sulfur (Fe–S) cluster biogenesis, and mitochondrial iron homeostasis. The most common Fe–S clusters in eukaryotes are the [2Fe–2S] and [4Fe–4S] clusters. Fe–S clusters are ancient biologic prosthetic groups essential for numerous biologic processes, including mitochondrial respiratory chain activity and various other enzymatic and regulatory functions. Mitochondrial iron overload is a prominent feature of the human Fe–S cluster assembly disorders [<a class="bibr" href="#sider-anemia.REF.rouault.2008.398" rid="sider-anemia.REF.rouault.2008.398">Rouault & Tong 2008</a>, <a class="bibr" href="#sider-anemia.REF.sheftel.2010.302" rid="sider-anemia.REF.sheftel.2010.302">Sheftel et al 2010</a>]. It is possible that ABCB7 transports Fe-S clusters and/or an as-yet-unknown regulatory molecule from mitochondria to convey the signal that mitochondria have sufficient iron (<a class="figpopup" href="/books/NBK1321/figure/sider-anemia.F2/?report=objectonly" target="object" rid-figpopup="figsideranemiaF2" rid-ob="figobsideranemiaF2">Figure 2</a>). Then, if either Fe-S cluster synthesis or heme synthesis is disrupted, the cytosolic/nuclear compartment would perceive mitochondrial iron deficiency and could respond by significantly increasing mitochondrial iron stores.</p><p>See <a href="/books/NBK1321/bin/sider-anemia-pathogenesis.pdf">Additional information on pathogenesis</a> (pdf).</p><p><b>Gene structure.</b>
|
|
<i>ABCB7</i> comprises 16 exons [<a class="bibr" href="#sider-anemia.REF.shimada.1998.115" rid="sider-anemia.REF.shimada.1998.115">Shimada et al 1998</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>]. For a detailed summary of gene and protein information, see <a href="/books/NBK1321/?report=reader#sider-anemia.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1321/table/sider-anemia.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobsideranemiaTmoleculargenetictesting">Table 2</a> and <a href="/books/NBK1321/table/sider-anemia.T.abcb7_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsideranemiaTabcb7pathogenicvariants">Table 3</a>. Only four unrelated families with XLSA/A have been reported, each with a distinct missense variant. It is worth noting that the identified pathogenic variants are missense variants with intermediate severity.</p><ul><li class="half_rhythm"><div><a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al [1985]</a> reported four males in two generations and a fifth male from an unrelated family who were affected. In the four members of the first kindred, <a class="bibr" href="#sider-anemia.REF.allikmets.1999.743" rid="sider-anemia.REF.allikmets.1999.743">Allikmets et al [1999]</a> found a hemizygous pathogenic missense variant in exon 9 (c.1203T>G; p.Ile401Met) resulting in a substitution in the fifth putative transmembrane region of the ABCB7 protein. This pathogenic variant was identified in the heterozygous state in female obligate carriers.</div></li><li class="half_rhythm"><div><a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al [2000]</a> reported two affected brothers with XLSA/A and found a hemizygous pathogenic missense variant in exon 10 (c.1300G>A; p.Glu434Lys) causing a substitution adjacent to the sixth putative transmembrane region of the ABCB7 protein; this variant was present in one allele in their mother.</div></li><li class="half_rhythm"><div><a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al [2001]</a> reported a family with two affected brothers and two affected maternal uncles. In the two brothers and in one uncle who was still alive, <a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al [2001]</a> found a hemizygous pathogenic missense variant in exon 10 (c.1234G>C; p.Val412Leu) leading to a substitution in the last of six putative transmembrane regions of the ABCB7 protein. The mother was heterozygote for this variant.</div></li><li class="half_rhythm"><div><a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al [2012]</a> reported a male child with a novel hemizygous pathogenic missense variant in exon 6 (c.627A>T; p.Glu209Asp) causing a substitution adjacent to the second transmembrane domain at the mitochondrial side; his mother was heterozygous for the same variant.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsideranemiaTabcb7pathogenicvariants"><a href="/books/NBK1321/table/sider-anemia.T.abcb7_pathogenic_variants/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobsideranemiaTabcb7pathogenicvariants"><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="sider-anemia.T.abcb7_pathogenic_variants"><a href="/books/NBK1321/table/sider-anemia.T.abcb7_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsideranemiaTabcb7pathogenicvariants">Table 3. </a></h4><p class="float-caption no_bottom_margin"><i>ABCB7</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p>See <a href="/books/NBK1321/bin/sider-anemia-genetics.pdf">Additional information on genetics of XLSA/A</a> (pdf).</p><p><b>Normal gene product.</b> The ATP-binding cassette, subfamily B, member 7 protein (ABCB7) belongs to the adenosine triphosphate-binding cassette transporter superfamily; its yeast ortholog, Atm1p, plays a central role in the maturation of cytosolic iron-sulfur (Fe-S) cluster-containing proteins [<a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>]. <i>ABCB7</i> contributes to the production of heme during the differentiation of erythroid cells [<a class="bibr" href="#sider-anemia.REF.taketani.2003.3274" rid="sider-anemia.REF.taketani.2003.3274">Taketani et al 2003</a>]. It is also thought to transport a component required for the maturation of cytosolic Fe-S clusters from the mitochondrion to the cytosol [<a class="bibr" href="#sider-anemia.REF.napier.2005.1867" rid="sider-anemia.REF.napier.2005.1867">Napier et al 2005</a>]. Thus, the mitochondrion appears to be important in both heme synthesis and in the biogenesis of Fe-S clusters.</p><p><i>ABCB7</i> is highly expressed in bone marrow as well as in the cerebellum, which may explain why males with ABCB7 deficiency have ataxia [<a class="bibr" href="#sider-anemia.REF.allikmets.1999.743" rid="sider-anemia.REF.allikmets.1999.743">Allikmets et al 1999</a>, <a class="bibr" href="#sider-anemia.REF.ye.a" rid="sider-anemia.REF.ye.a">Ye & Rouault 2010a</a>, <a class="bibr" href="#sider-anemia.REF.ye.2010b.4945" rid="sider-anemia.REF.ye.2010b.4945">Ye & Rouault 2010b</a>]. The ataxia observed in XLSA/A may be related to the damage mediated by the iron loading in the mitochondrion and/or disruption to mitochondrial iron homeostasis in neural cells [<a class="bibr" href="#sider-anemia.REF.napier.2005.1867" rid="sider-anemia.REF.napier.2005.1867">Napier et al 2005</a>].</p><p><b>Abnormal gene product.</b> Complementation studies in yeast suggest that the human mutated ATP-binding cassette, subfamily B, member 7 proteins (ABCB7) are caused by mild, partial loss-of-function alleles [<a class="bibr" href="#sider-anemia.REF.allikmets.1999.743" rid="sider-anemia.REF.allikmets.1999.743">Allikmets et al 1999</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al 2000</a>] that result in diminished cytosolic Fe-S cluster protein.</p><p><a class="bibr" href="#sider-anemia.REF.pondarr_.2006.953" rid="sider-anemia.REF.pondarr_.2006.953">Pondarré et al [2006]</a> created a conditional knockout allele of the murine ortholog <i>Abcb7</i> and formally demonstrated that XLSA/A is caused by partial-loss-of-function variants that directly or indirectly inhibit heme biosynthesis [<a class="bibr" href="#sider-anemia.REF.pondarr_.2007.3567" rid="sider-anemia.REF.pondarr_.2007.3567">Pondarré et al 2007</a>]. Indeed, mutation leading to a significant loss of protein function must be lethal as illustrated by a knockout mouse model [<a class="bibr" href="#sider-anemia.REF.pondarr_.2006.953" rid="sider-anemia.REF.pondarr_.2006.953">Pondarré et al 2006</a>].</p></div></div><div id="sider-anemia.References"><h2 id="_sider-anemia_References_">References</h2><div id="sider-anemia.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.allikmets.1999.743">Allikmets R, Raskind WH, Hutchinson A, Schueck ND, Dean M, Koeller DM. Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). <span><span class="ref-journal">Hum Mol Genet. </span>1999 May;<span class="ref-vol">8</span>:743–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10196363" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10196363</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.bekri.2000.3256">Bekri S, Kispal G, Lange H, Fitzsimons E, Tolmie J, Lill R, Bishop DF. Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. <span><span class="ref-journal">Blood. </span>2000;<span class="ref-vol">96</span>:3256–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11050011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11050011</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.bergmann.2010.273">Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. <span><span class="ref-journal">Pediatr Blood Cancer. </span>2010 Feb;<span class="ref-vol">54</span>:273–8.</span> [<a href="/pmc/articles/PMC2843911/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2843911</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19731322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19731322</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.bernard.2008.194">Bernard G, Shevell M. The wobbly child: an approach to inherited ataxias. <span><span class="ref-journal">Semin Pediatr Neurol. </span>2008;<span class="ref-vol">15</span>:194–208.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19073328" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19073328</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.boddaert.2007.401">Boddaert N, Le Quan Sang KH, Rötig A, Leroy-Willig A, Gallet S, Brunelle F, Sidi D, Thalabard JC, Munnich A, Cabantchik ZI. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. <span><span class="ref-journal">Blood. </span>2007 Jul 1;<span class="ref-vol">110</span>:401–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17379741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17379741</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.boultwood.2008.e1970">Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, Littlewood TJ, Malcovati L, Della Porta MG, Jädersten M, Killick S, Giagounidis A, Bowen D, Hellström-Lindberg E, Cazzola M, Wainscoat JS. The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. <span><span class="ref-journal">PLoS ONE. </span>2008;<span class="ref-vol">3</span>:e1970. </span> [<a href="/pmc/articles/PMC2276313/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2276313</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18398482" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18398482</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.burke.2007.73">Burke MA, Ardehali H. Mitochondrial ATP-binding cassette proteins. <span><span class="ref-journal">Transl Res. </span>2007;<span class="ref-vol">150</span>:73–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17656326" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17656326</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.bykhovskaya.2004.1303">Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). <span><span class="ref-journal">Am J Hum Genet. </span>2004;<span class="ref-vol">74</span>:1303–8.</span> [<a href="/pmc/articles/PMC1182096/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1182096</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15108122" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15108122</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.calmels.2009.e6379">Calmels N, Schmucker S, Wattenhofer-Donzé M, Martelli A, Vaucamps N, Reutenauer L, Messaddeq N, Bouton C, Koenig M, Puccio H. The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia. <span><span class="ref-journal">PLoS One. </span>2009 Jul 24;<span class="ref-vol">4</span>:e6379. </span> [<a href="/pmc/articles/PMC2710521/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2710521</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19629184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19629184</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.camaschella.2008.27">Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. <span><span class="ref-journal">Br J Haematol. </span>2008;<span class="ref-vol">143</span>:27–38.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18637800" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18637800</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.camaschella.2007.1353">Camaschella C, Campanella A, De Falco L, Boschetto L, Merlini R, Silvestri L, Levi S, Iolascon A. The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. <span><span class="ref-journal">Blood. </span>2007;<span class="ref-vol">110</span>:1353–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17485548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17485548</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.dhooghe.2012.730">D'Hooghe M, Selleslag D, Mortier G, Van Coster R, Vermeersch P, Billiet J, Bekri S. X-linked sideroblastic anemia and ataxia: a new family with identification of a fourth ABCB7 gene mutation. <span><span class="ref-journal">Eur J Paediatr Neurol. </span>2012 Nov;<span class="ref-vol">16</span>:730–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22398176" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22398176</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.fleming.2002.270">Fleming MD. The genetics of inherited sideroblastic anemias. <span><span class="ref-journal">Semin Hematol. </span>2002;<span class="ref-vol">39</span>:270–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12382202" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12382202</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.fujiwara.2013.675">Fujiwara T, Harigae H. Pathophysiology and genetic mutations in congenital sideroblastic anemia. <span><span class="ref-journal">Pediatr Int. </span>2013;<span class="ref-vol">55</span>:675–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24003969" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24003969</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.guernsey.2009.651">Guernsey DL, Jiang H, Campagna DR, Evans SC, Ferguson M, Kellogg MD, Lachance M, Matsuoka M, Nightingale M, Rideout A, Saint-Amant L, Schmidt PJ, Orr A, Bottomley SS, Fleming MD, Ludman M, Dyack S, Fernandez CV, Samuels ME. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. <span><span class="ref-journal">Nat Genet. </span>2009 Jun;<span class="ref-vol">41</span>:651–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19412178" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19412178</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.hart.1981.220">Hart D, Piomelli S. Simultaneous quantitation of zinc protoporphyrin and free protoporphyrin in erythrocytes by acetone extraction. <span><span class="ref-journal">Clin Chem. </span>1981;<span class="ref-vol">27</span>:220–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7460270" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7460270</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.hellier.2001.65">Hellier KD, Hatchwell E, Duncombe AS, Kew J, Hammans SR. X-linked sideroblastic anaemia with ataxia: another mitochondrial disease? <span><span class="ref-journal">J Neurol Neurosurg Psychiatry. </span>2001;<span class="ref-vol">70</span>:65–9.</span> [<a href="/pmc/articles/PMC1763461/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1763461</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11118249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11118249</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.holland.2011.1">Holland IB. ABC transporters, mechanisms and biology: an overview. <span><span class="ref-journal">Essays Biochem. </span>2011;<span class="ref-vol">50</span>:1–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21967049" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21967049</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.kakhlon.2010.187">Kakhlon O, Breuer W, Munnich A, Cabantchik ZI. Iron redistribution as a therapeutic strategy for treating diseases of localized iron accumulation. <span><span class="ref-journal">Can J Physiol Pharmacol. </span>2010;<span class="ref-vol">88</span>:187–96.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20393584" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20393584</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.maguire.2001.910">Maguire A, Hellier K, Hammans S, May A. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L. <span><span class="ref-journal">Br J Haematol. </span>2001;<span class="ref-vol">115</span>:910–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11843825" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11843825</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.moitra.2011.29">Moitra K, Dean M. Evolution of ABC transporters by gene duplication and their role in human disease. <span><span class="ref-journal">Biol Chem. </span>2011;<span class="ref-vol">392</span>:29–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21194360" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21194360</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.napier.2005.1867">Napier I, Ponka P, Richardson DR. Iron trafficking in the mitochondrion: novel pathways revealed by disease. <span><span class="ref-journal">Blood. </span>2005;<span class="ref-vol">105</span>:1867–74.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15528311" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15528311</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.nikpour.2013.889">Nikpour M, Scharenberg C, Liu A, Conte S, Karimi M, Mortera-Blanco T, Giai V, Fernandez-Mercado M, Papaemmanuil E, Högstrand K, Jansson M, Vedin I, Stephen Wainscoat J, Campbell P, Cazzola M, Boultwood J, Grandien A, Hellström-Lindberg E. The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts. <span><span class="ref-journal">Leukemia. </span>2013;<span class="ref-vol">27</span>:889–96.</span> [<a href="/pmc/articles/PMC3794445/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3794445</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23070040" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23070040</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.pagon.1985.267">Pagon RA, Bird TD, Detter JC, Pierce I. Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder. <span><span class="ref-journal">J Med Genet. </span>1985;<span class="ref-vol">22</span>:267–73.</span> [<a href="/pmc/articles/PMC1049446/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1049446</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/4045952" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4045952</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.piomelli.1975.1519">Piomelli S, Lamola AA, Poh-Fitzpatrick MF, Seaman C, Harber LC. Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro. <span><span class="ref-journal">J Clin Invest. </span>1975;<span class="ref-vol">56</span>:1519–27.</span> [<a href="/pmc/articles/PMC333130/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC333130</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1202082" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1202082</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.pondarr_.2006.953">Pondarré C, Antiochos BB, Campagna DR, Clarke SL, Greer EL, Deck KM, McDonald A, Han AP, Medlock A, Kutok JL, Anderson SA, Eisenstein RS, Fleming MD. The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulphur cluster biogenesis. <span><span class="ref-journal">Hum Mol Genet. </span>2006;<span class="ref-vol">15</span>:953–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16467350" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16467350</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.pondarr_.2007.3567">Pondarré C, Campagna DR, Antiochos B, Sikorski L, Mulhern H, Fleming MD. Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. <span><span class="ref-journal">Blood. </span>2007;<span class="ref-vol">109</span>:3567–9.</span> [<a href="/pmc/articles/PMC1852240/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1852240</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17192398" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17192398</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.raskind.1991.335">Raskind WH, Wijsman E, Pagon RA, Cox TC, Bawden MJ, May BK, Bird TD. X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13. <span><span class="ref-journal">Am J Hum Genet. </span>1991;<span class="ref-vol">48</span>:335–41.</span> [<a href="/pmc/articles/PMC1683027/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1683027</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1671320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1671320</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.riley.2010.52">Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giegé R, Bahlo M, Christodoulou J. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2010 Jul 9;<span class="ref-vol">87</span>:52–9.</span> [<a href="/pmc/articles/PMC2896778/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2896778</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20598274" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20598274</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.rouault.2008.398">Rouault TA, Tong WH. Iron-sulfur cluster biogenesis and human disease. <span><span class="ref-journal">Trends Genet. </span>2008;<span class="ref-vol">24</span>:398–407.</span> [<a href="/pmc/articles/PMC2574672/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2574672</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18606475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18606475</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.sears.2004.249">Sears DA, Udden MM. Pappenheimer bodies: a brief historical review. <span><span class="ref-journal">Am J Hematol. </span>2004;<span class="ref-vol">75</span>:249–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15054821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15054821</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.sheftel.2010.302">Sheftel A, Stehling O, Lill R. Iron-sulfur proteins in health and disease. <span><span class="ref-journal">Trends Endocrinol Metab. </span>2010;<span class="ref-vol">21</span>:302–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20060739" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20060739</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.shimada.1998.115">Shimada Y, Okuno S, Kawai A, Shinomiya H, Saito A, Suzuki M, Omori Y, Nishino N, Kanemoto N, Fujiwara T, Horie M, Takahashi E. Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. <span><span class="ref-journal">J Hum Genet. </span>1998;<span class="ref-vol">43</span>:115–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9621516" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9621516</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.stemmler.2010.26737">Stemmler TL, Lesuisse E, Pain D, Dancis A. Frataxin and mitochondrial FeS cluster biogenesis. <span><span class="ref-journal">J Biol Chem. </span>2010;<span class="ref-vol">285</span>:26737–43.</span> [<a href="/pmc/articles/PMC2930671/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2930671</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20522547" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20522547</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.taketani.2003.3274">Taketani S, Kakimoto K, Ueta H, Masaki R, Furukawa T. Involvement of ABC7 in the biosynthesis of heme in erythroid cells: interaction of ABC7 with ferrochelatase. <span><span class="ref-journal">Blood. </span>2003;<span class="ref-vol">101</span>:3274–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12480705" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12480705</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.ye.a">Ye H, Rouault TA. Erythropoiesis and iron sulfur cluster biogenesis. Adv Hematol 2010a;2010. [<a href="/pmc/articles/PMC2939393/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2939393</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20862391" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20862391</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.ye.2010b.4945">Ye H, Rouault TA. Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. <span><span class="ref-journal">Biochemistry. </span>2010b;<span class="ref-vol">49</span>:4945–56.</span> [<a href="/pmc/articles/PMC2885827/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2885827</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20481466" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20481466</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.yoshida.2011.64">Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S. Frequent pathway mutations of splicing machinery in myelodysplasia. <span><span class="ref-journal">Nature. </span>2011;<span class="ref-vol">478</span>:64–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21909114" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21909114</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sider-anemia.REF.zutz.2009.681">Zutz A, Gompf S, Schagger H, Tampe R. Mitochondrial ABC proteins in health and disease. <span><span class="ref-journal">Biochim Biophys Acta. </span>2009;<span class="ref-vol">1787</span>:681–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19248758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19248758</span></a>]</div></p></li></ul></div></div><div id="sider-anemia.Chapter_Notes"><h2 id="_sider-anemia_Chapter_Notes_">Chapter Notes</h2><div id="sider-anemia.Author_History"><h3>Author History</h3><p>Soumeya Bekri (2014-present)<br />Marc D'Hooghe, MD (2014-present)<br />Thomas D Bird, MD; University of Washington, Seattle (1998-2014)<br />Roberta A Pagon, MD; University of Washington, Seattle (1998-2014)<br />Pieter Vermeersch (2014-present)</p></div><div id="sider-anemia.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>20 August 2020 (ma) Chapter retired: extremely rare disorder</div></li><li class="half_rhythm"><div>3 April 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 April 2009 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>1 May 2008 (cd) Revision: sequencing of exons 5-16 and the intron/exon junctions available clinically</div></li><li class="half_rhythm"><div>24 March 2008 (cd) Revision: clinical testing not available</div></li><li class="half_rhythm"><div>1 March 2006 (me) Review posted live</div></li><li class="half_rhythm"><div>12 November 1998 (bp) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1321_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Soumeya Bekri</span><div class="affiliation small">Rouen University Hospital<br />Rouen, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="rf.neuor-uhc@irkeb.ayemuos" class="oemail">rf.neuor-uhc@irkeb.ayemuos</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Marc D'Hooghe</span>, MD<div class="affiliation small">Department of Neurology<br />Hospital St Jan<br />Bruges, Belgium<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.najtnisza@ehgoohd.cram" class="oemail">eb.najtnisza@ehgoohd.cram</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Pieter Vermeersch</span>, MD, PhD<div class="affiliation small">University Hospital Louvain<br />Louvain, Belgium<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.nevuelzu@hcsreemrev.reteip" class="oemail">eb.nevuelzu@hcsreemrev.reteip</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">March 1, 2006</span>; Last Update: <span itemprop="dateModified">April 3, 2014</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>Bekri S, D'Hooghe M, Vermeersch P. X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2006 Mar 1 [Updated 2014 Apr 3]. 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/x-scid/?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/sedt/?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="figobsideranemiaTmeancorpuscularvolumem"><div id="sider-anemia.T.mean_corpuscular_volume_m" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Mean Corpuscular Volume (MCV fl) in XLSA/A</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1321/table/sider-anemia.T.mean_corpuscular_volume_m/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sider-anemia.T.mean_corpuscular_volume_m_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Group</th><th id="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mean Corpuscular Volume (MCV fl)</th></tr></thead><tbody><tr><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Normal male</b>
|
|
</td><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">89.1 ± 5.01</td></tr><tr><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Normal female</b>
|
|
</td><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">87.6 ± 5.5</td></tr><tr><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Affected male</b>
|
|
</td><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">58 to 68</td></tr><tr><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Carrier female</b>
|
|
</td><td headers="hd_h_sider-anemia.T.mean_corpuscular_volume_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">83 to 90</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"><a class="bibr" href="#sider-anemia.REF.pagon.1985.267" rid="sider-anemia.REF.pagon.1985.267">Pagon et al [1985]</a> (4 affected males and 3 obligate carrier females)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsideranemiaTmoleculargenetictesting"><div id="sider-anemia.T.molecular_genetic_testing" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in X-Linked Sideroblastic Anemia and Ataxia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1321/table/sider-anemia.T.molecular_genetic_testing/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sider-anemia.T.molecular_genetic_testing_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Male Probands with a Pathogenic Variant Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ABCB7</i>
|
|
</td><td headers="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>2, 3</sup></td><td headers="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/4 families tested <sup>4</sup></td></tr><tr><td headers="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_sider-anemia.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown, none reported <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="sider-anemia.TF.2.1"><p class="no_margin">See <a href="/books/NBK1321/?report=reader#sider-anemia.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein. See <a href="#sider-anemia.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="sider-anemia.TF.2.2"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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>3. </dt><dd><div id="sider-anemia.TF.2.3"><p class="no_margin">Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation may require additional testing by deletion/duplication analysis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="sider-anemia.TF.2.4"><p class="no_margin"><a class="bibr" href="#sider-anemia.REF.allikmets.1999.743" rid="sider-anemia.REF.allikmets.1999.743">Allikmets et al [1999]</a>, <a class="bibr" href="#sider-anemia.REF.bekri.2000.3256" rid="sider-anemia.REF.bekri.2000.3256">Bekri et al [2000]</a>, <a class="bibr" href="#sider-anemia.REF.hellier.2001.65" rid="sider-anemia.REF.hellier.2001.65">Hellier et al [2001]</a>, <a class="bibr" href="#sider-anemia.REF.maguire.2001.910" rid="sider-anemia.REF.maguire.2001.910">Maguire et al [2001]</a>, <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al [2012]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="sider-anemia.TF.2.5"><p class="no_margin">Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="sider-anemia.TF.2.6"><p class="no_margin">No deletions/duplications of <i>ABCB7</i> have been reported to cause XLSA/A.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsideranemiamolgenTA"><div id="sider-anemia.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>X-Linked Sideroblastic Anemia and Ataxia: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1321/table/sider-anemia.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sider-anemia.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sider-anemia.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sider-anemia.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sider-anemia.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sider-anemia.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_sider-anemia.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sider-anemia.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sider-anemia.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/22" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ABCB7</i>
|
|
</a>
|
|
</td><td headers="hd_b_sider-anemia.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=22" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xq13<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_sider-anemia.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O75027" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATP-binding cassette sub-family B member 7, mitochondrial</a>
|
|
</td><td headers="hd_b_sider-anemia.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.LOVD.nl/ABCB7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCB7 @ LOVD</a>
|
|
</td><td headers="hd_b_sider-anemia.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=ABCB7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCB7</a>
|
|
</td><td headers="hd_b_sider-anemia.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ABCB7[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCB7</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="sider-anemia.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="figobsideranemiamolgenTB"><div id="sider-anemia.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for X-Linked Sideroblastic Anemia and Ataxia (<a href="/omim/300135,301310" 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/NBK1321/table/sider-anemia.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sider-anemia.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/300135" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300135</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ATP-BINDING CASSETTE, SUBFAMILY B, MEMBER 7; ABCB7</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/301310" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">301310</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ANEMIA, SIDEROBLASTIC, AND SPINOCEREBELLAR ATAXIA; ASAT</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsideranemiaTabcb7pathogenicvariants"><div id="sider-anemia.T.abcb7_pathogenic_variants" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p><i>ABCB7</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/NBK1321/table/sider-anemia.T.abcb7_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sider-anemia.T.abcb7_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sider-anemia.T.abcb7_pathogenic_variants_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_sider-anemia.T.abcb7_pathogenic_variants_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_sider-anemia.T.abcb7_pathogenic_variants_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_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.627A>T</td><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu209Asp</td><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/entrez/viewer.fcgi?val=NM_004299.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004299<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="/entrez/viewer.fcgi?val=NP_004290.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004290<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td></tr><tr><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1203T>G</td><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ile401Met</td></tr><tr><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1234G>C</td><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val412Leu</td></tr><tr><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1300G>A</td><td headers="hd_h_sider-anemia.T.abcb7_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu434Lys</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="http://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></div></div></div></article><article data-type="fig" id="figobsideranemiaF1"><div id="sider-anemia.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1321/bin/sider-anemia-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Ringed sideroblast</p><p>Prussian blue staining of the bone marrow aspirate (x1000) showing a normal erythroid precursor (straight arrow) and a ringed sideroblast containing many iron granules around the nucleus (curved arrow).</p><p>From <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al [2012]</a> with permission</p></div></div></article><article data-type="fig" id="figobsideranemiaF2"><div id="sider-anemia.F2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1321/bin/sider-anemia-Image002.jpg" alt="Figure 2. " /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>Fe-S cluster biogenesis, heme synthesis and hypothetic effects of defects in ABCB7</p><p>Adapted from <a class="bibr" href="#sider-anemia.REF.dhooghe.2012.730" rid="sider-anemia.REF.dhooghe.2012.730">D'Hooghe et al [2012]</a> with permission</p></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 portal106 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|