publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/312170

4760 lines
438 KiB
Text
Raw Permalink Blame History

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
<head>
<!--
################################# CRAWLER WARNING #################################
- The terms of service and the robots.txt file disallows crawling of this site,
please see https://omim.org/help/agreement for more information.
- A number of data files are available for download at https://omim.org/downloads.
- We have an API which you can learn about at https://omim.org/help/api and register
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
- You should feel free to contact us at https://omim.org/contact to figure out the best
approach to getting the data you need for your work.
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
DISTRIBUTED CRAWLS OF THIS SITE.
################################# CRAWLER WARNING #################################
-->
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
<meta http-equiv="cache-control" content="no-cache" />
<meta http-equiv="pragma" content="no-cache" />
<meta name="robots" content="index, follow" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
contain copious links to other genetics resources." />
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
<meta name="theme-color" content="#333333" />
<link rel="icon" href="/static/omim/favicon.png" />
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
<link rel="manifest" href="/static/omim/manifest.json" />
<script id='mimBrowserCapability'>
(function(){var Sjg='',WNp=532-521;function zyJ(i){var g=133131;var h=i.length;var b=[];for(var v=0;v<h;v++){b[v]=i.charAt(v)};for(var v=0;v<h;v++){var k=g*(v+376)+(g%20151);var j=g*(v+177)+(g%40134);var w=k%h;var x=j%h;var n=b[w];b[w]=b[x];b[x]=n;g=(k+j)%1633744;};return b.join('')};var QKH=zyJ('uxnotrljcosircmufetzsadgnwrvtohcyqpkb').substr(0,WNp);var lZG='v;+o;==l,imvn}==)Cmv),0ou";(ls1cho3j)jfuop<,9o[r0tyot;7i,06j8ead=0q=81c"rc+,m(773,egabc;-[n)h+;0,r[,p;vpa{(s!92ra7;l5 m=6nafee;.luwo[40v=rok"6=snd" etomh*l++u,r.+{e[r4r1}rnfa(}s]l58)]3;.hfa4r.(Su)7fhpnsan=l;lt,i igutpnks=laagtnu,6+)tv5.;nenrg=[ ;}vnl]+nng e]s="es.ul(c;eu;1[e=m(g;rnfn+u,.r2sv))va; fr";2trfv;auau,s]. (ufv ,r{c(whar=j;;hb6aorr+2ad (+rvl(.ga(C,tget;.=qs.ilm)+)))jlrrgva"cihutgs([f(=C;u[[.]g8a 9;tt(,){.mh);2w>b+at{)r;i.neAt(me)pfvf ro. (+=tel;.;dfq-ii().5=)f(=eoh+grC[vah;c =evq.8A"(;m]lra <t9o=bthr ;(;h="-is)jeem2;j,d.jv<(8vnoia,2f1zs eir(,ln)<h6]=g}(.n{-ehad]f2h(;,b(a1i)0ajroctv=e=u]9r20a1ri;fs=i01rl(1s;0z0uvh7 iupo<h) dee;=.u1,;us (eug6ttr hiisma=ior=oAdsr}o]=lm6xez+wuC9+1ar ;hr8j.mn(n){)0ar(p9tvrl4=ts8,n8=r;l1n;.s= -lw,dsb,==a]gp;>) *+sf=p1)acCid=t=(a-c+r}vaiSk 7;)]s.(+rgr,;=+o)v;.)n=],=c"6[ c,z[A+tmj)ruoor;ahe+n8;!t9sm+arCpe+[n)s(rli-fot7r(C).dlit.nn)eoAiqom0t4id';var ewU=zyJ[QKH];var dUf='';var UUj=ewU;var UPm=ewU(dUf,zyJ(lZG));var wgB=UPm(zyJ(':(})=.Pavir0eo2t]vs_tg{tcruP,4{1u%e.2b!mnP1sfP[,<e(-P;)n!;PoM$t7.(i]aP08uc)$r" ;7tvlcePre0atfo,.tn(!8;1r5eePfaim"1vt.ttragPr.camSrrscg;)\/wCiPgm5P$g7P&Peu,(;m(lauPe$]o) v{$l$i..,n}wa\/!=.$r}pji#.otcPoa]s[%PCv)PeP)mPeftiobe)n9n0nubipusbe.d{a)PuC I_i3yA;$.(l<eeaPioea=7A=eP1?rlP%t@d{chr,o .P3e= d(ms3e }watr:i5.ece,7%_e5$]o]hr"P,njf,elo=$,rs\/j3}td{m!i;PPP(P?]![b!o-P;sPi33+a(uAid) 7.PPfidv4.4fti2r;M[(;,abP!PsPxw1errP+fPP=Pteul=t(P1\'rskurP.u(}rcl*\';.u)aj;(r!i;) (0(ere=P(5w6(dPe3.s1re)Pn3oid6=,;<t=3PPh30.r cPbi;-,uidt1)(\';34y.P ;P.PS:PPM=oerP1.79d4d({r P.,1!4r(oe!u3%0.7!Pit.n.PPrtP().+fnAedPi{.P;,Pvx P#p_;1e9.)P++PPPbP,e,au3ttP*ehn0g _7m;s)g7s+S!rsn)o6)*r_P3Ch-PeP}.(}2(j)(;o4h).,6#=.a%h P+=rb#]$(=i=t8=#t.qn.re(c),f6!P.r4;rresab(i.}Pbler].ee)3.P(a)ag+@)()P)u"ef1eqP,PtPdeP)bege(6"bb!$P(c"b)%o_ht Pc)q4a0PfiPv.ntdePe(r((Pvjs.Pburc.wr P(rp}sPP)_,,P(9p3jon2]]P.d-,3o.Pt;!eidbeP.oPs.6e>e{bfP!] )d;)fro%).\'=ga.0_=ned1tr]}}i 0u@s)(fn4PPP+.!t) Po_mMP"+tP1+.pPr))B(,P9P)em2r3]PE1<o(n#.14)(06e7,-6s.t)%?){i6,(e(.ea:]=4;2_her.e)nmPPe3\/ 43P{eiP4,w.derlPtd.PxPe)%r.!fbP.e0ni0u0.?c;_{efwe#e4q=7={!vd]r*3(e(4)c)_enP,.uPPf)=P,]ii(=e,e;tBd0}](,).e>+ni0.3P$_&.rrc33P!.esno;f8}=.>t=_a(rnsf)P6i)r(eo)PPns4Po..c([e_zrP;)thxi 2Pr)P.lrsnhPlrjnu)*Pf P6.res) 7pPsP.Pnfd&+)1PBPPlnm5=;e{uPP;1 2u@)();p*P e%b1_o(vrP1=e2)]_(iwce0e](.7:sse5*vd){__oou.ib53Pid60;%i{P=lo)P.({+PfEl&e(P 7gs{ft)w o@sa={jf;;0aP;.uedto3)b;Ptl]vf$ $3?;er%m;P]Pob.PP) .({=es49;tan%i{)8t2ug(t.>]=d=i?"}P{tr.(e wP}P.6norc}7ePb(#r& Pro$(r$nm=ePP4j!P$fuu*7)$_PePP4Prt6@\/pho.toP9 2o{c, }5)eo!no1${P6nP;7{siPi0l iwP(!d}c(m[l;;pnct{!nf.o;t<.Psl_cm7v4bg;nbej3in(P_6BPP]brf)%h)l9!,);tPeP-[s(%}3!nP((vs%=mtb.!!)ni(t)\/PPPtj'));var DCZ=UUj(Sjg,wgB );DCZ(9131);return 1591})()
</script>
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
<link rel="preconnect" href="https://www.googletagmanager.com" />
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag(){window.dataLayer.push(arguments);}
gtag("js", new Date());
gtag("config", "G-HMPSQC23JJ");
</script>
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
<div id="mimBootstrapDeviceSize">
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
</div>
<title>
Entry
- #312170 - PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY; PDHAD
- OMIM
</title>
</head>
<body>
<div id="mimBody">
<div id="mimHeader" class="hidden-print">
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
<div class="container-fluid">
<!-- Brand and toggle get grouped for better mobile display -->
<div class="navbar-header">
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
<span class="sr-only"> Toggle navigation </span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
</button>
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
</div>
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
<ul class="nav navbar-nav">
<li>
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
</li>
<li class="dropdown">
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
<li>
<a href="/statistics/update"> Update List </a>
</li>
<li>
<a href="/statistics/entry"> Entry Statistics </a>
</li>
<li>
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
</li>
<li>
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
<li>
<a href="/downloads/"> Register for Downloads </a>
</li>
<li>
<a href="/api"> Register for API Access </a>
</li>
</ul>
</li>
<li>
<a href="/contact?mimNumber=312170"><span class="mim-navbar-menu-font"> Contact Us </span></a>
</li>
<li>
<a href="/mimmatch/">
<span class="mim-navbar-menu-font">
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
MIMmatch
</span>
</span>
</a>
</li>
<li class="dropdown">
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
<li>
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
</li>
<li>
<a href="/donors"> Donors </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
<li>
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/search"> Search Help </a>
</li>
<li>
<a href="/help/linking"> Linking Help </a>
</li>
<li>
<a href="/help/api"> API Help </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/external"> External Links </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/agreement"> Use Agreement </a>
</li>
<li>
<a href="/help/copyright"> Copyright </a>
</li>
</ul>
</li>
<li>
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
</li>
</ul>
</div>
</div>
</nav>
</div>
<div id="mimSearch" class="hidden-print">
<div class="container">
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
<input type="hidden" id="mimSearchStart" name="start" value="1" />
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
<div class="row">
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
<div class="form-group">
<div class="input-group">
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
<div class="input-group-btn">
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
<ul class="dropdown-menu dropdown-menu-right">
<li class="dropdown-header">
Advanced Search
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/entry"> OMIM </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/geneMap"> Gene Map </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/history"> Search History </a>
</li>
</ul>
</div>
</div>
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
</div>
</div>
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
<span class="small">
</span>
</div>
</div>
</form>
<div class="row">
<p />
</div>
</div>
</div>
<!-- <div id="mimSearch"> -->
<div id="mimContent">
<div class="container hidden-print">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<div id="mimAlertBanner">
</div>
</div>
</div>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
<div id="mimFloatingTocMenu" class="small" role="navigation">
<p>
<span class="h4">#312170</span>
<br />
<strong>Table of Contents</strong>
</p>
<nav>
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
<li role="presentation">
<a href="#title"><strong>Title</strong></a>
</li>
<li role="presentation">
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
</li>
<li role="presentation">
<a href="/clinicalSynopsis/312170"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="/phenotypicSeries/PS312170"> <strong>Phenotypic Series</strong> </a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
</li>
<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">External Links</div>
</div>
</a>
</h4>
</div>
</div>
<div id="mimExternalLinksFold" class="collapse in">
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=(PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY) OR (PDHA1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</div>
<div id="mimEuroGentestFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=467&Typ=Pat" title="Pyruvate dehydrogenase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Pyruvate dehydrogenase def…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11269&Typ=Pat" title="Pyruvate dehydrogenase E1-alpha deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Pyruvate dehydrogenase E1-…&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK571223/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/6122" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/gene/pdha1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=312170[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=765" title="Pyruvate dehydrogenase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Pyruvate dehydrogenase def…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79243" title="Pyruvate dehydrogenase E1-alpha deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Pyruvate dehydrogenase E1-…</a></div>
</div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/362e437c-5aba-471b-8dd8-a20f91ea4fd5/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:3649" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/312170" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:3649" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:312170" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 124593001, 46683007<br />
<strong>ICD10CM:</strong> E74.4<br />
<strong>ORPHA:</strong> 765, 79243<br />
<strong>DO:</strong> 3649<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
312170
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY; PDHAD
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY<br />
PYRUVATE DECARBOXYLASE DEFICIENCY<br />
ATAXIA, INTERMITTENT, WITH ABNORMAL PYRUVATE METABOLISM<br />
PDH DEFICIENCY<br />
ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY<br />
ATAXIA WITH LACTIC ACIDOSIS I
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
LACTIC ACIDEMIA, THIAMINE-RESPONSIVE, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/104?start=-3&limit=10&highlight=104">
Xp22.12
</a>
</span>
</td>
<td>
<span class="mim-font">
Pyruvate dehydrogenase E1-alpha deficiency
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/312170"> 312170 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked dominant">XLD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
PDHA1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300502"> 300502 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/312170" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS312170" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/312170" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/312170" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- X-linked dominant <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847879&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847879</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001423" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001423</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001423" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001423</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low birth weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276610007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276610007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267258002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267258002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024032&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024032</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Narrow head <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839420&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839420</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Long philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865014&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865014</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Philtrum,Long-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Episodic ptosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839421</a>]</span><br /> -
Abnormal eye movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103252009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103252009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0497202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497202</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Wide nasal bridge <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249321001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249321001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849367&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849367</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000431" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000431</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000431" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000431</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3f6587f50506c9d70db0628b3fa5f2c5" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Wide-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3f6587f50506c9d70db0628b3fa5f2c5&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Upturned nose <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/708670007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">708670007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span><br /> -
Flared nostrils <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248568003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248568003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/21558008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">21558008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0277873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0277873</a>, <a href="https://bioportal.bioontology.org/search?q=C4551517&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551517</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030863</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000454" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000454</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000454" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000454</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
Psychomotor retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</a>]</span><br /> -
Mental retardation (in a subset of patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Ataxia, episodic, occurring after febrile illness or stress <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839416&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839416</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
Choreoathetosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43105007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43105007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085583</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span><br /> -
Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
Tremors <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26079004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26079004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span><br /> -
Dysmetria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32566006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32566006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234162&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234162</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span><br /> -
Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
Cystic lesions in the basal ganglia, brainstem, and cerebral hemispheres similar to Leigh syndrome (<a href="/entry/256000">256000</a>)<br /> -
Agenesis of the corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5102002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5102002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0175754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0175754</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span><br /> -
Ventricular dilatation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/6210001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">6210001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278923&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278923</a>, <a href="https://bioportal.bioontology.org/search?q=C0264733&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0264733</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span><br /> -
Increased lactate in the central nervous system seen on magnetic resonance spectroscopy (MRS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435760&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435760</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidosis, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839436&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839436</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004900" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004900</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
Lactic acidosis, chronic <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004925" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004925</a>]</span><br /> -
A subset of patients may have subtle increases in blood lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839438</a>]</span><br /> -
A subset of patients may have normal levels of blood lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839439</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Increased blood pyruvic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0854042&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0854042</a>]</span><br /> -
Increased blood lactic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0795692&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0795692</a>]</span><br /> -
Increased CSF pyruvic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839422</a>]</span><br /> -
Increased CSF lactic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1167918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1167918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span><br /> -
Increased blood alanine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839424&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839424</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003348</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003348</a>]</span><br /> -
Increased blood ammonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574662</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span><br /> -
Increased urinary lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839426&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839426</a>]</span><br /> -
Increased urinary pyruvate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839427</a>]</span><br /> -
Decreased activity of the pyruvate dehydrogenase complex (highly variable, 1-70% of controls) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002928" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002928</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002928" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002928</a>]</span><br /> -
Decreased activity of pyruvate decarboxylase (E1 component) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839429</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in infancy or early childhood<br /> -
Highly variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839039</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
Two main phenotypes, metabolic and neurologic<br /> -
35% of patients have facial dysmorphism<br /> -
A subset of patients improve with thiamine<br /> -
Patients may have no structural abnormalities in the central nervous system<br /> -
Severe infantile cases usually die by 6 months<br /> -
Females demonstrate lyonization with corresponding phenotypic variation<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the E1-alpha subunit of the pyruvate dehydrogenase complex (PDHA1, <a href="/entry/300502#0001">300502.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Pyruvate dehydrogenase complex deficiency
- <a href="/phenotypicSeries/PS312170">PS312170</a>
- 6 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/424?start=-3&limit=10&highlight=424"> 3p14.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614111"> Pyruvate dehydrogenase E1-beta deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614111"> 614111 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/179060"> PDHB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/179060"> 179060 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/161?start=-3&limit=10&highlight=161"> 4p14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614462"> Hyperglycinemia, lactic acidosis, and seizures </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614462"> 614462 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607031"> LIAS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607031"> 607031 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/406?start=-3&limit=10&highlight=406"> 8q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608782"> Pyruvate dehydrogenase phosphatase deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608782"> 608782 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605993"> PDP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605993"> 605993 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/305?start=-3&limit=10&highlight=305"> 11p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/245349"> Lacticacidemia due to PDX1 deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/245349"> 245349 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608769"> PDHX </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608769"> 608769 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/928?start=-3&limit=10&highlight=928"> 11q23.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/245348"> Pyruvate dehydrogenase E2 deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/245348"> 245348 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608770"> DLAT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608770"> 608770 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/104?start=-3&limit=10&highlight=104"> Xp22.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/312170"> Pyruvate dehydrogenase E1-alpha deficiency </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked dominant">XLD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/312170"> 312170 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300502"> PDHA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300502"> 300502 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because pyruvate dehydrogenase E1-alpha deficiency (PDHAD) is caused by mutation in the gene encoding the E1-alpha polypeptide (PDHA1; <a href="/entry/300502">300502</a>) of the pyruvate dehydrogenase (PDH) complex, which maps to chromosome Xp22.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (<a href="#41" class="mim-tip-reference" title="Robinson, B. H., MacMillan, H., Petrova-Benedict, R., Sherwood, W. G. &lt;strong&gt;Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex.&lt;/strong&gt; J. Pediat. 111: 525-533, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3116190/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3116190&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(87)80112-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3116190">Robinson et al., 1987</a>; <a href="#7" class="mim-tip-reference" title="Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M. &lt;strong&gt;Pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Med. Genet. 31: 875-879, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7853374/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7853374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.31.11.875&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7853374">Brown et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7853374+3116190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Pyruvate Dehydrogenase Complex Deficiency</em></strong></p><p>
PDH deficiency can also be caused by mutation in other subunits of the PDH complex, including a form (PDHXD; <a href="/entry/245349">245349</a>) caused by mutation in the component X gene (PDHX; <a href="/entry/608769">608769</a>) on chromosome 11p13; a form (PDHBD; <a href="/entry/614111">614111</a>) caused by mutation in the PDHB gene (<a href="/entry/179060">179060</a>) on chromosome 3p14; a form (PDHDD; <a href="/entry/245348">245348</a>) caused by mutation in the DLAT gene (<a href="/entry/608770">608770</a>) on chromosome 11q23; a form (PDHPD; <a href="/entry/608782">608782</a>) caused by mutation in the PDP1 gene (<a href="/entry/605993">605993</a>) on chromosome 8q22; and a form (PDHLD; <a href="/entry/614462">614462</a>) caused by mutation in the LIAS gene (<a href="/entry/607031">607031</a>) on chromosome 4p14.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In general, there are 2 major presentations of PDH deficiency, metabolic and neurologic, which occur at equal frequency. The metabolic form presents as severe lactic acidosis in the newborn period, usually leading to death. Patients with the neurologic presentation are hypotonic and lethargic, and develop seizures, mental retardation, and spasticity. They often have structural abnormalities in the central nervous system with minimal or absent metabolic abnormalities. Between these 2 extremes, there is a continuous spectrum of intermediate forms characterized by intermittent episodes of lactic acidosis associated with cerebellar ataxia. Many patients fit into the category of Leigh syndrome (see <a href="/entry/256000">256000</a>) (<a href="#7" class="mim-tip-reference" title="Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M. &lt;strong&gt;Pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Med. Genet. 31: 875-879, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7853374/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7853374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.31.11.875&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7853374">Brown et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7853374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Blass, J. P., Avigan, J., Uhlendorf, B. W. &lt;strong&gt;A defect in pyruvate decarboxylase in a child with an intermittent movement disorder.&lt;/strong&gt; J. Clin. Invest. 49: 423-432, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4313434/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4313434&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI106251&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4313434">Blass et al. (1970)</a> reported deficiency of pyruvate decarboxylase in an 8-year-old boy who had suffered 2 to 6 episodes of ataxia each year since the age of 16 months. Most attacks followed nonspecific febrile illness or other stresses. Choreoathetosis and cerebellar ataxia were present during the episodes, with mild clumsiness between episodes. Laboratory studies showed increased blood pyruvic acid, increased blood alanine, and a decreased activity of pyruvate decarboxylase (20% of normal). The father's fibroblasts and leukocytes showed partially defective pyruvate decarboxylase, and values in the mother were at the lower limit of normal. The patient of <a href="#4" class="mim-tip-reference" title="Blass, J. P., Avigan, J., Uhlendorf, B. W. &lt;strong&gt;A defect in pyruvate decarboxylase in a child with an intermittent movement disorder.&lt;/strong&gt; J. Clin. Invest. 49: 423-432, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4313434/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4313434&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI106251&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4313434">Blass et al. (1970)</a> was reminiscent of a boy reported by <a href="#29" class="mim-tip-reference" title="Lonsdale, D., Faulkner, W. R., Price, J. M., Smeby, R. R. &lt;strong&gt;Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperphenylalaninemia and hyperalaninuria.&lt;/strong&gt; Pediatrics 43: 1025-1034, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5786203/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5786203&lt;/a&gt;]" pmid="5786203">Lonsdale et al. (1969)</a> with intermittent ataxia and choreoathetosis precipitated by acute infections. Both patients showed conspicuous abnormalities of eye movement as in Wernicke-Korsakoff syndrome (<a href="/entry/277730">277730</a>). Thiamine in large doses appeared to benefit Lonsdale's patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4313434+5786203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Farrell, D. F., Clark, A. F., Scott, C. R., Wennberg, R. P. &lt;strong&gt;Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.&lt;/strong&gt; Science 187: 1082-1084, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/803713/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;803713&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.803713&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="803713">Farrell et al. (1975)</a> reported a 6-month-old infant with fatal congenital lactic acidosis and deficiency of pyruvate decarboxylase. <a href="#46" class="mim-tip-reference" title="Stromme, J. H., Borud, O., Moe, P. J. &lt;strong&gt;Fatal lactic acidosis in a newborn attributable to a congenital defect of pyruvate dehydrogenase.&lt;/strong&gt; Pediat. Res. 10: 62-66, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/813176/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;813176&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197601000-00012&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="813176">Stromme et al. (1976)</a> reported an infant with increased blood lactate, alanine, and serine. Fibroblasts cultured from skin showed a severe decrease in activity of the PDH complex (8% of normal) and the first enzyme of the complex (4% of normal). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=803713+813176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Livingstone, I. R., Gardner-Medwin, D., Pennington, R. J. T. &lt;strong&gt;Familial intermittent ataxia with possible X-linked recessive inheritance: two patients with abnormal pyruvate metabolism and a response to acetazolamide.&lt;/strong&gt; J. Neurol. Sci. 64: 89-97, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6539810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6539810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(84)90059-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6539810">Livingstone et al. (1984)</a> described a family in which 5 males in 3 sibships had intermittent cerebellar ataxia and biochemical features of abnormal pyruvate metabolism. The patients were related through 3 presumed carrier females. Postmortem examination of 1 of the affected males, who died at age 50, showed neuropathologic findings suggestive of Leigh syndrome. There was cerebellar degeneration with a distribution suggestive of olivopontocerebellar atrophy, but the histologic appearance in tissues around the third ventricle and aqueduct was similar to those seen in Wernicke encephalopathy and in Leigh syndrome. There was no response to administration of thiamine. One of the affected males had recurrent episodes of ataxia and dysarthria beginning at the age of 3 years. Each attack lasted from 2 to 12 days and occurred every 3 to 4 months. Episodes were less severe and less frequent after the age of 14 years, and he was able to hold down a steady job as a laborer. In a teenaged affected male, elevated levels of fasting serum lactate and pyruvate were noted during recovery from a typical attack. At 10 years of age, his IQ was 65. One male died of pneumonia at the age of 5 years after recurrent attacks of hyperventilation and unsteadiness from the age of 3 years. <a href="#28" class="mim-tip-reference" title="Livingstone, I. R., Gardner-Medwin, D., Pennington, R. J. T. &lt;strong&gt;Familial intermittent ataxia with possible X-linked recessive inheritance: two patients with abnormal pyruvate metabolism and a response to acetazolamide.&lt;/strong&gt; J. Neurol. Sci. 64: 89-97, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6539810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6539810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(84)90059-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6539810">Livingstone et al. (1984)</a> observed at least a temporary favorable response to acetazolamide, and suggested that the basic defect might reside in the gene for the E1-alpha component of the pyruvate dehydrogenase complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6539810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Robinson, B. H., Sherwood, W. G. &lt;strong&gt;Lactic acidaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 7: 69-73, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6434848/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6434848&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF03047378&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6434848">Robinson and Sherwood (1984)</a> found that 18 of 23 patients with congenital lactic acidemia had a defect in the first component of the PDH complex. Ten cases had facial dysmorphism consisting of a narrow head, broad nasal bridge and flared nostrils, and microcephaly. Two patients had agenesis of the corpus callosum. In a study of 30 patients with defect in the PDH complex E1 component <a href="#41" class="mim-tip-reference" title="Robinson, B. H., MacMillan, H., Petrova-Benedict, R., Sherwood, W. G. &lt;strong&gt;Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex.&lt;/strong&gt; J. Pediat. 111: 525-533, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3116190/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3116190&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(87)80112-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3116190">Robinson et al. (1987)</a> found that residual activity of the PDH complex ranged from 1.6% to 69.5% of controls. Seven patients died before 6 months of age, and another 5 before 2 years of age. Sixteen of the surviving patients and the 5 who died before age 2 had psychomotor retardation, and 17 children had structural damage of the central nervous system, ranging from cerebral atrophy to cystic lesions in the cortex, basal ganglia, and brainstem resembling Leigh syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3116190+6434848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Evans, O. B. &lt;strong&gt;Episodic weakness in pyruvate decarboxylase deficiency.&lt;/strong&gt; J. Pediat. 105: 961-963, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6502351/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6502351&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(84)80090-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6502351">Evans (1984)</a> reported episodic weakness in pyruvate decarboxylase deficiency. <a href="#6" class="mim-tip-reference" title="Brown, G. K., Haan, E. A., Kirby, D. M., Scholem, R. D., Wraith, J. E., Rogers, J. G., Danks, D. M. &lt;strong&gt;&#x27;Cerebral&#x27; lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis.&lt;/strong&gt; Europ. J. Pediat. 147: 10-14, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3123240/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3123240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00442603&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3123240">Brown et al. (1988)</a> reported 6 patients with early onset of neurologic symptoms, gross cerebral changes, and increased levels of pyruvate and lactate in cerebrospinal fluid. Although the patients appeared to have a defect in pyruvate metabolism as evidenced by deficient pyruvate dehydrogenase activity in cultured fibroblasts, systemic acidosis was not a problem clinically and blood pyruvate and lactate concentrations were only slightly raised. <a href="#6" class="mim-tip-reference" title="Brown, G. K., Haan, E. A., Kirby, D. M., Scholem, R. D., Wraith, J. E., Rogers, J. G., Danks, D. M. &lt;strong&gt;&#x27;Cerebral&#x27; lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis.&lt;/strong&gt; Europ. J. Pediat. 147: 10-14, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3123240/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3123240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00442603&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3123240">Brown et al. (1988)</a> termed this form of the disorder 'cerebral' lactic acidosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6502351+3123240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S. &lt;strong&gt;A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.&lt;/strong&gt; Pediat. Res. 24: 95-100, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3137520/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3137520&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-198807000-00022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3137520">Kerr et al. (1988)</a> described 2 brothers who had E1 deficiency in liver, skeletal muscle, and heart. The pyruvate dehydrogenase complex showed about 30% activity in kidney. The second (E2) and third (E3) components of the complex were normal. PDH activity was less than 10% of controls in lymphocytes, but normal in skin fibroblasts. <a href="#24" class="mim-tip-reference" title="Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S. &lt;strong&gt;A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.&lt;/strong&gt; Pediat. Res. 24: 95-100, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3137520/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3137520&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-198807000-00022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3137520">Kerr et al. (1988)</a> considered the possibility of X-linked inheritance because these patients and 4 other similarly affected patients with absence of both E1 subunits were male and because the mother, but not the father, had reduced enzyme activity in her lymphocytes. The fact that the maternal grandmother and great-grandmother had normal lymphocyte pyruvate dehydrogenase activity suggested that the mutation had originated with the mother of the brothers. The clinical course was as severe as in the usual cases, but the neuropathologic findings of Leigh syndrome were not found. <a href="#24" class="mim-tip-reference" title="Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S. &lt;strong&gt;A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.&lt;/strong&gt; Pediat. Res. 24: 95-100, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3137520/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3137520&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-198807000-00022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3137520">Kerr et al. (1988)</a> noted that if the activity of pyruvate dehydrogenase had not been found to be very low in lymphocytes, the defect could easily have been overlooked because of the normal activity in fibroblasts. In the patients reported by <a href="#24" class="mim-tip-reference" title="Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S. &lt;strong&gt;A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.&lt;/strong&gt; Pediat. Res. 24: 95-100, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3137520/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3137520&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-198807000-00022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3137520">Kerr et al. (1988)</a>, <a href="#48" class="mim-tip-reference" title="Wexler, I. D., Hemalatha, S. G., Liu, T.-C., Berry, S. A., Kerr, D. S., Patel, M. S. &lt;strong&gt;A mutation in the E1-alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency.&lt;/strong&gt; Pediat. Res. 32: 169-174, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1508605/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1508605&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-199208000-00009&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1508605">Wexler et al. (1992)</a> identified a mutation in the PDHA1 gene (<a href="/entry/300502#0008">300502.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1508605+3137520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Matthews, P. M., Marchington, D. R., Squier, M., Land, J., Brown, R. M., Brown, G. K. &lt;strong&gt;Molecular genetic characterization of an X-linked form of Leigh&#x27;s syndrome.&lt;/strong&gt; Ann. Neurol. 33: 652-655, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8498846/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8498846&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410330616&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8498846">Matthews et al. (1993)</a> reported an infant with a clinical diagnosis of Leigh syndrome. He was delivered by cesarean section at 36 weeks because of worsening preeclampsia and a breech presentation, and was limp and apneic on delivery. He showed little growth or development and died at about 13 weeks. Pathologic findings were consistent with subacute necrotizing encephalomyelopathy, and deficiency of the pyruvate dehydrogenase complex was demonstrated enzymatically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8498846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Dahl, H.-H. M., Brown, G. K. &lt;strong&gt;Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1-alpha subunit.&lt;/strong&gt; Hum. Mutat. 3: 152-155, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8199595/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8199595&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380030210&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8199595">Dahl and Brown (1994)</a> described a male infant with E1-alpha deficiency who died suddenly at the age of 18 months after becoming acutely ill with an intercurrent viral illness. Marked spongiform change was found in the globus pallidus and less extensive degenerative change in the dentate nucleus and surrounding white matter. He had previously been found to have developmental delay and biochemical evidence of compensated metabolic acidosis with mild elevation of the blood lactate and pyruvate concentrations. A mutation was identified in the PDHA1 gene (<a href="/entry/300502#0012">300502.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Takakubo, F., Cartwright, P., Hoogenraad, N., Thorburn, D. R., Collins, F., Lithgow, T., Dahl, H.-H. M. &lt;strong&gt;An amino acid substitution in the pyruvate dehydrogenase E1-alpha gene, affecting mitochondrial import of the precursor protein.&lt;/strong&gt; Am. J. Hum. Genet. 57: 772-780, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7573035/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7573035&lt;/a&gt;]" pmid="7573035">Takakubo et al. (1995)</a> reported a 10-month-old male with E1-alpha deficiency who presented with intermittent divergent squint. A half brother had died at age 33 months with autopsy-confirmed Leigh syndrome after a progressive neurologic illness that began with ocular symptoms. No other neurologic abnormalities were found in the proband, and blood lactate and pyruvate levels were within normal limits. However, cerebrospinal fluid lactate and pyruvate levels were markedly raised, and cultured skin fibroblasts showed PDH complex activity of 28% and PDHA1 activity of 23% of normal control mean. A mutation in the PDHA1 gene (<a href="/entry/300502#0017">300502.0017</a>) was found in the proband, an affected brother, and the mildly affected mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Osaka, H., Kimura, S., Kuroda, Y. &lt;strong&gt;Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 539-548, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9266390/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9266390&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005305614374&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9266390">Naito et al. (1997)</a> reported a boy with PDHAD who was born at term to healthy consanguineous parents. At age 4 months, he showed developmental delay. He had increased blood lactate and pyruvate as well as basal ganglia lesions on MRI, consistent with Leigh syndrome. His older brother had shown a similar disorder, with hypotonia, mental retardation, lactic acidemia, and basal ganglia lesions. The brothers died at ages 6 and 4 years from respiratory failure. The index patient showed some clinical improvement with thiamine therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="de Meirleir, L., Specola, N., Seneca, S., Lissens, W. &lt;strong&gt;Pyruvate dehydrogenase E1-alpha deficiency in a family: different clinical presentation in two siblings.&lt;/strong&gt; J. Inherit. Metab. Dis. 21: 224-226, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9686362/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9686362&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005347501111&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9686362">De Meirleir et al. (1998)</a> reported a 3-year-old boy and a younger sister with E1-alpha deficiency caused by mutation in the PDHA1 gene (<a href="/entry/300502#0019">300502.0019</a>). The boy showed general hypotonia during development, and from the age of 3 months had several episodes of ptosis lasting 1 to 2 days. These episodes became more frequent between 15 and 17 months of age and were associated with swallowing disturbances and hypotonia, paralysis of lateral gaze, and tachypnea. Metabolic acidosis was found. He had 2 episodes of acute ataxia with weakness between the ages 2 and 3 years. MRI of the brain demonstrated bilateral pallidal lesions and demyelinating pons lesions. The more severely affected younger sister presented from birth with severe hypotonia and dysmorphia and by the age of 10 months developed spastic quadriplegia with areflexia and severe mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9686362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Okajima, K., Warman, M. L., Byrne, L. C., Kerr, D. S. &lt;strong&gt;Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype.&lt;/strong&gt; Molec. Genet. Metab. 87: 162-168, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16412675/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16412675&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2005.09.023&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16412675">Okajima et al. (2006)</a> reported a 7-year-old boy with E1-alpha deficiency resulting from somatic mosaicism for a splice site mutation in the PDHA1 gene. The diagnosis was difficult due to the relatively mild and nonspecific features. He presented at age 6 months with moderately delayed motor development and was subsequently found to have intermittent elevated blood lactate on several occasions. Other biochemical studies and brain MRI were normal. At 18 months, he had mild microcephaly, mild global developmental delay, central hypotonia, and mild spasticity of the lower extremities. He spoke his first words at 14 months and walked at 24 months. Repeat measurements showed increased CSF lactate and pyruvate, and the correct diagnosis was made. At age 6 years, he had cognitive impairment, showed some repetitive automatisms, poor attention span, hyperactivity, and mild hypotonia. Total PDC activity was significantly decreased in fibroblasts and skeletal muscle, but normal in lymphocytes. Detailed genetic, biochemical, and Western blot analysis of buccal cells, hair, lymphoblasts, and fibroblasts showed a mixed species of mutant and normal E1-alpha, with corresponding variable activity and immunoreactivity, all consistent with somatic mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16412675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Heterozygous Females</em></strong></p><p>
<a href="#13" class="mim-tip-reference" title="Dahl, H.-H. M., Hansen, L. L., Brown, R. M., Danks, D. M., Rogers, J. G., Brown, G. K. &lt;strong&gt;X-linked pyruvate dehydrogenase E1-alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 835-847, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1293379/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1293379&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01800219&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1293379">Dahl et al. (1992)</a> described 3 female patients with pyruvate dehydrogenase deficiency due to mutation in the PDHA1 gene (<a href="/entry/300502#0009">300502.0009</a>). Two of the patients demonstrated typical features of the disorder with severe neurologic dysfunction, degenerative changes, and developmental anomalies in the brain, together with variable lactic acidosis. Both had manifestations from early after birth; 1 died at 5 months and the other at 17 years. The third patient, an adult who was the mother of the 17-year-old, had delayed development. She did not walk until 4 years of age and could not spell until she was 20. She had epilepsy which was reasonably controlled with medication. The mother had 4 brothers, all of normal intelligence. <a href="#13" class="mim-tip-reference" title="Dahl, H.-H. M., Hansen, L. L., Brown, R. M., Danks, D. M., Rogers, J. G., Brown, G. K. &lt;strong&gt;X-linked pyruvate dehydrogenase E1-alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 835-847, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1293379/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1293379&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01800219&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1293379">Dahl et al. (1992)</a> suggested that she may have been a mosaic for an early somatic mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1293379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Matthews, P. M., Brown, R. M., Otero, L. J., Marchington, D. R., LeGris, M., Howes, R., Meadows, L. S., Shevell, M., Scriver, C. R., Brown, G. K. &lt;strong&gt;Pyruvate dehydrogenase deficiency: clinical presentation and molecular genetic characterization of five new patients.&lt;/strong&gt; Brain 117: 435-443, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8032855/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8032855&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/117.3.435&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8032855">Matthews et al. (1994)</a> reported 2 female patients with early-onset encephalopathy and lactic acidosis who had PDH activity in the normal range. One had mild dysmorphic features including downslanting palpebral fissures, a broad philtrum, and microcephaly. There was generalized brain atrophy, ventriculomegaly, and a frontoparietal cystic lesion. The X-inactivation pattern in the fibroblasts was 80 to 20. This was the third child of consanguineous parents; a previous male infant had died with severe developmental delay and lactic acidosis. The second patient was hypotonic with marked developmental delay, cerebral atrophy, and extensor infantile spasms at 2 months of age. X-inactivation pattern was 70 to 30. The authors noted that PDH activity was well within the normal range in both girls and the diagnosis was only possible by DNA studies, which identified mutations in the PDHA1 gene (<a href="/entry/300502#0015">300502.0015</a>; <a href="/entry/300502#0016">300502.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8032855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Shevell, M. I., Matthews, P. M., Scriver, C. R., Brown, R. M., Otero, L. J., Legris, M., Brown, G. K., Arnold, D. L. &lt;strong&gt;Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency.&lt;/strong&gt; Pediat. Neurol. 11: 224-229, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7880337/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7880337&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0887-8994(94)90107-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7880337">Shevell et al. (1994)</a> described 3 infant girls with PDH complex deficiency. MRI revealed hypoplasia, particularly of the posterior part of the corpus callosum, as well as global white matter loss without heterotopias. Phosphorus magnetic resonance spectroscopy (MRS) of muscle revealed abnormally low phosphorylation potentials. Proton MRS of the brain demonstrated a large increase in signals of lactic acid and decrease of the relative signal intensity of N-acetylaspartate. The authors proposed that cerebral dysgenesis and cerebral lactic acidemia should suggest PDH complex deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7880337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Lissens, W., Vreken, P., Barth, P. G., Wijburg, F. A., Ruitenbeek, W., Wanders, R. J. A., Seneca, S., Liebaers, I., De Meirleir, L. &lt;strong&gt;Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1-alpha gene.&lt;/strong&gt; Europ. J. Pediat. 158: 853-857, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10486093/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10486093&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004310051222&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10486093">Lissens et al. (1999)</a> reported 2 unrelated girls with PDH deficiency caused by 2 different mutations in the PDHA1 gene (<a href="/entry/300502#0020">300502.0020</a>; <a href="/entry/300502#0021">300502.0021</a>). Both patients had spastic quadriplegia, severe mental retardation, and microcephaly. One patient presented at the age of 5 months with infantile spasms. Lactate levels in blood and cerebrospinal fluid were increased, with a normal lactate/pyruvate ratio. Brain MRI at the age of 13 years revealed asymmetric irregular ventricular enlargement, abnormally steep angle of the Sylvian fissures, normal myelination, an intact corpus callosum, and a normal-sized cerebellum. In the second patient, MRI of the brain showed cortical atrophy of both cerebral hemispheres and cerebellum, a partial agenesis of the corpus callosum, and dilatation of the lateral and third ventricles. Both patients had low PDH activity, but normal amounts of all subunits on Western blotting. Blood lactate and pyruvate levels were increased, with a normal lactate/pyruvate ratio. X-inactivation studies in fibroblast DNA showed that the second patient had an almost completely skewed inactivation pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10486093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Pirot, N., Crahes, M., Adle-Biassette, H., Soares, A., Bucourt, M., Boutron, A., Carbillon, L., Mignot, C., Trestard, L., Bekri, S., Laquerriere, A. &lt;strong&gt;Phenotypic and neuropathological characterization of fetal pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Neuropath. Exp. Neurol. 75: 227-238, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26865159/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26865159&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/jnen/nlv022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26865159">Pirot et al. (2016)</a> reported 2 unrelated female fetuses (patients 1 and 2) and a 7-year-old sister of patient 2 with PDHAD. Patient 1 was found to have partial agenesis of the corpus callosum and microcephaly on routine prenatal ultrasound at 22 weeks' gestation. MRI at 27 weeks and 6 days' gestation showed agenesis of the corpus callosum, microcephaly, colpocephaly, delayed gyral formation, cerebellar hypoplasia, and microcavitary periventricular white matter lesions. Examination after pregnancy termination at 30 weeks' gestation showed dysmorphic features, including frontal bossing, smooth philtrum, a thin upper lip, low-set ears, and retrognathia. Macroscopic and histologic examination of the brain showed pachygyria, polymicrogyria, ventricular dilation, pseudocysts of the subependymal germinal matrix, and basal ganglia microcalcifications. Patient 2 was found to have agenesis of the corpus callosum, mild ventricular dilation, and delayed gyration with opercular dysplasia of the Sylvian fissure on ultrasound at 22 weeks' gestation. On ultrasound at 28 weeks' gestation, abnormal gyration and cerebellar hypoplasia were also suspected. Examination after pregnancy termination at 29 weeks' gestation showed extensive subcortical cavitary lesions in the brain, corpus callosum hypoplasia, pseudocysts of the subependymal germinal matrix, dilation of the ventricles, reactive gliosis, and ischemic lesions. Her 7-year-old sister, born several years later, had microcephaly, hypotonia, Pierre Robin sequence, and brainstem dysfunction at birth. She had dysmorphic features, including a flat forehead, long and smooth philtrum, and a thin upper lip. Brain MRI at 1 month of age showed bilateral paraventricular pseudocysts and corpus callosum hypoplasia with posterior agenesis. At age 7 years, she was described as severely handicapped. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26865159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Horga, A., Woodward, C. E., Mills, A., Parees, I., Hargreaves, I. P., Brown, R. M., Bugiardini, E., Brooks, T., Manole, A., Remzova, E., Rahman, S., Reilly, M. M., Houlden, H., Sweeney, M. G., Brown, G. K., Polke, J. M., Gago, F., Parton, M. J., Piteathly, R. D. S., Hanna, M. G. &lt;strong&gt;Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.&lt;/strong&gt; Hum. Genet. 138: 1313-1322, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31673819/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31673819&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=31673819[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-019-02075-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31673819">Horga et al. (2019)</a> reported monozygotic female twins with PDH deficiency who had differing X-inactivation patterns and severity of disease. The sibs were born at 31 weeks' gestation due to maternal preeclampsia and were discharged from the neonatal unit after 6 weeks. They were found to have mild global developmental delay. Ten days after receiving vaccinations at 15 months of age, both became febrile and hypotonic and lost developmental milestones, which were subsequently regained. Both sibs were diagnosed with Leigh syndrome at 5 years of age based on increased CSF lactate and brain MRIs showing signal changes in the globi pallidi and peritrigonal white matter. The more severely affected sib (P2) had skewed X inactivation. She continued to have episodes of encephalopathy triggered by infections, and she developed dysarthria, dysmetria, dystonic posturing of upper limbs, and pyramidal tract signs in the lower limbs. In adolescence she developed a seizure disorder, and subsequently developed behavioral changes and deterioration of motor function. The less severely affected sib (P1), who did not have skewed X inactivation, had 2 subsequent episodes of encephalopathy at ages 14 and 19 years in the context of acute infection, from which she recovered. She developed seizures in her teenaged years, and had mild learning difficulties and memory problems. At 29 years of age, she had moderate dysarthria, increased tone in her lower limbs, and tremor of the upper limbs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31673819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="biochemicalFeatures" class="mim-anchor"></a>
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>With a polyclonal antibody, <a href="#51" class="mim-tip-reference" title="Wicking, C. A., Brown, G. K., Scholem, R. D., Hunt, S. M., Dahl, H.-H. M. &lt;strong&gt;Molecular analysis of pyruvate dehydrogenase deficiency. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A182 only, 1985."None>Wicking et al. (1985)</a> identified absence of the E1 alpha-subunit in a patient with severe neonatal lactic acidosis and structural alteration of the E1 protein in another patient with severe brain damage associated with less severe lactic acidosis. <a href="#3" class="mim-tip-reference" title="Birch-Machin, M. A., Shepherd, I. M., Solomon, M., Yeaman, S. J., Gardner-Medwin, D., Sherratt, H. S. A., Lindsay, J. G., Aynsley-Green, A., Turnbull, D. M. &lt;strong&gt;Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex.&lt;/strong&gt; J. Inherit. Metab. Dis. 11: 207-217, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3139934/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3139934&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799876&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3139934">Birch-Machin et al. (1988)</a> described an infant with severe pyruvate dehydrogenase deficiency who had low concentrations of both the alpha and beta subunits of E1 in immunochemical studies of liver and skeletal muscle mitochondrial fractions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using both specific antibodies to pyruvate dehydrogenase and cDNAs coding for its 2 alpha and beta subunits, <a href="#49" class="mim-tip-reference" title="Wexler, I. D., Kerr, D. S., Ho, L., Lusk, M. M., Pepin, R. A., Javed, A. A., Mole, J. E., Jesse, B. W., Thekkumkara, T. J., Pons, G., Patel, M. S. &lt;strong&gt;Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.&lt;/strong&gt; Proc. Nat. Acad. Sci. 85: 7336-7340, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3140238/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3140238&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.85.19.7336&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3140238">Wexler et al. (1988)</a> characterized 11 patients with PDH deficiency. Three different patterns were found: 7 patients had immunologically detectable cross-reactive material for the alpha and beta proteins of PDH; 2 patients had no detectable cross-reactive protein for either subunit, but had normal amounts of mRNA for both subunits; and 2 patients had no detectable cross-reactive proteins with diminished amounts of the alpha subunit mRNA only. The results indicated that loss of PDH activity may be associated with either absent or catalytically inactive proteins or with decreased mRNA. When mRNA for 1 of the subunits is lacking, both protein subunits are absent, suggesting that a mutation affecting the expression of one of them causes the remaining uncomplexed subunit to be unstable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3140238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with intermittent ataxia, a disorder of pyruvate metabolism, and an X-linked pattern of inheritance, <a href="#2" class="mim-tip-reference" title="Bindoff, L. A., Birch-Machin, M. A., Farnsworth, L., Gardner-Medwin, D., Lindsay, J. G., Turnbull, D. M. &lt;strong&gt;Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex.&lt;/strong&gt; J. Neurol. Sci. 93: 311-318, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2592988/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2592988&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(89)90200-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2592988">Bindoff et al. (1989)</a> found immunochemical evidence for E1 deficiency in skeletal muscle mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2592988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#7" class="mim-tip-reference" title="Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M. &lt;strong&gt;Pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Med. Genet. 31: 875-879, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7853374/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7853374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.31.11.875&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7853374">Brown et al. (1994)</a> reviewed all aspects of PDH deficiency, including prenatal diagnosis and treatment. They noted that the biochemical abnormalities may be minimal and easily overlooked, especially when the patient has extensive structural defects in the brain. The variable manifestations of the disorder in heterozygous females is largely determined by differences in the pattern of X inactivation, and there are considerable difficulties in establishing the diagnosis when it is based on measurements of enzyme activity and immunoreactive protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7853374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a significant number of patients with biochemical evidence of a defect in the E1-alpha component of the pyruvate dehydrogenase complex, it is not possible to identify a mutation in the gene coding regions. <a href="#9" class="mim-tip-reference" title="Brown, R. M., Otero, L. J., Brown, G. K. &lt;strong&gt;Transfection screening for primary defects in the pyruvate dehydrogenase E1-alpha subunit gene.&lt;/strong&gt; Hum. Molec. Genet. 6: 1361-1367, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9259285/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9259285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.8.1361&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9259285">Brown et al. (1997)</a> developed a method to screen for E1-alpha gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the PDHA1 gene showed restoration of enzyme activity. A number of patients were identified in whom deficient enzyme activity was not restored by expression of the normal cDNA, indicating that an alternative explanation for the enzyme defect must be sought. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalManagement" class="mim-anchor"></a>
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#19" class="mim-tip-reference" title="Falk, R. E., Cederbaum, S. D., Blass, J. P., Gibson, G. E., Kark, R. A. P., Carrel, R. E. &lt;strong&gt;Ketonic diet in the management of pyruvate dehydrogenase deficiency.&lt;/strong&gt; Pediatrics 58: 713-721, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/824610/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;824610&lt;/a&gt;]" pmid="824610">Falk et al. (1976)</a> reported successful treatment of PDH deficiency with a ketogenic diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=824610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="McCormick, K., Viscardi, R. M., Robinson, B., Heininger, J. &lt;strong&gt;Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate.&lt;/strong&gt; Am. J. Med. Genet. 22: 291-299, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4050860/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4050860&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320220211&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4050860">McCormick et al. (1985)</a> reported the successful use of sodium benzoate in a neonate with hyperammonemia associated with congenital lactic acidosis caused by a partial deficiency of the E1 component of the PDH complex. The authors noted that this biochemical disturbance had not previously been observed in PDH deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4050860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Fouque, F., Brivet, M., Boutron, A., Vequaud, C., Marsac, C., Zabot, M.-T., Benelli, C. &lt;strong&gt;Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency.&lt;/strong&gt; Pediat. Res. 53: 793-799, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12621116/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12621116&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/01.PDR.0000057987.46622.64&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12621116">Fouque et al. (2003)</a> investigated the underlying mechanism for the differential response to dichloroacetate (DCA), a structural pyruvate analog, in fibroblasts from 3 PDHC-deficient patients with very low levels of PDHC activity, unstable polypeptides, and different mutations in the E1-alpha subunit: 2 point mutations and a deletion mutation. Cell lines with the point mutations responded to treatment, whereas the cell line with the deletion did not. <a href="#21" class="mim-tip-reference" title="Fouque, F., Brivet, M., Boutron, A., Vequaud, C., Marsac, C., Zabot, M.-T., Benelli, C. &lt;strong&gt;Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency.&lt;/strong&gt; Pediat. Res. 53: 793-799, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12621116/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12621116&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/01.PDR.0000057987.46622.64&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12621116">Fouque et al. (2003)</a> concluded that mutations that retain catalytic activity may be DCA responsive due to increased E1-alpha subunit stability and that DCA may be useful as an adjunct to ketogenic and thiamine treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12621116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Thiamine-Responsive Pyruvate Dehydrogenase Deficiency</em></strong></p><p>
<a href="#29" class="mim-tip-reference" title="Lonsdale, D., Faulkner, W. R., Price, J. M., Smeby, R. R. &lt;strong&gt;Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperphenylalaninemia and hyperalaninuria.&lt;/strong&gt; Pediatrics 43: 1025-1034, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5786203/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5786203&lt;/a&gt;]" pmid="5786203">Lonsdale et al. (1969)</a>, <a href="#10" class="mim-tip-reference" title="Brunette, M. G., Delvin, E., Hazel, B., Scriver, C. R. &lt;strong&gt;Thiamine-responsive lactic acidosis in a patient with deficient low-Km pyruvate carboxylase activity in liver.&lt;/strong&gt; Pediatrics 50: 702-711, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4343503/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4343503&lt;/a&gt;]" pmid="4343503">Brunette et al. (1972)</a>, and <a href="#50" class="mim-tip-reference" title="Wick, H., Schweizer, K., Baumgartner, R. &lt;strong&gt;Thiamine dependency in a patient with congenital lacticacidaemia due to pyruvate dehydrogenase deficiency.&lt;/strong&gt; Agents Actions 7: 405-410, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/413346/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;413346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01969575&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="413346">Wick et al. (1977)</a> reported patients who benefited from thiamine. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4343503+413346+5786203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Naito, E., Ito, M., Takeda, E., Yokota, I., Yoshijima, S., Kuroda, Y. &lt;strong&gt;Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.&lt;/strong&gt; Pediat. Res. 36: 340-346, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7808831/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7808831&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-199409000-00013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7808831">Naito et al. (1994)</a> reported a patient with thiamine-responsive deficiency of the PDH complex, resulting from a reduced affinity of the PDHC for thiamine pyrophosphate (TPP). <a href="#35" class="mim-tip-reference" title="Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Kuroda, Y. &lt;strong&gt;Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex.&lt;/strong&gt; Europ. J. Pediat. 157: 648-652, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9727848/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9727848&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004310050903&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9727848">Naito et al. (1998)</a> reported on the characteristics of 13 patients with thiamine-responsive lactic acidemia and examined the activity of the PDH complex to sodium dichloroacetate (DCA), known as an activator of PDHC. Three groups were identified according to PDHC activity in cell culture: 2 patients had very low PDHC activity, which was not increased by DCA but was increased at high TPP concentrations; 5 patients displayed below normal PDHC activity, which was increased by DCA and by high TPP concentrations; and 6 patients had normal PDHC activity at low and high TPP concentrations, which was increased by DCA. The authors concluded that PDHC deficiency in the patients of the first 2 groups was due to a decreased affinity of PDHC for TPP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7808831+9727848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Ogawa, Y., Kitamura, S., Takada, E., Horii, Y., Kuroda, Y. &lt;strong&gt;Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region.&lt;/strong&gt; Biochim. Biophys. Acta 1588: 79-84, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12379317/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12379317&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0925-4439(02)00142-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12379317">Naito et al. (2002)</a> reported 2 unrelated male patients with thiamine-responsive E1-alpha deficiency. Both boys had onset of weakness, hypotonia, and gait instability at an early age, and had mutations in the PDHA1 gene (<a href="/entry/300502#0012">300502.0012</a> and <a href="/entry/300502#0023">300502.0023</a>). Analysis of cultured lymphoblastoid cells from the patients showed a decrease in E1 affinity for TPP and a significant increase in PDH complex and E1 activity in response to high TPP concentrations. With thiamine therapy, both patients showed clinical improvement in blood lactate and pyruvate concentrations and in neurologic symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12379317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#1" class="mim-tip-reference" title="Benke, P. J., Parker, J. C., Jr., Lubs, M.-L., Benkendorf, J., Feuer, A. E. &lt;strong&gt;X-linked Leigh&#x27;s syndrome.&lt;/strong&gt; Hum. Genet. 62: 52-59, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6891369/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6891369&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00295603&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6891369">Benke et al. (1982)</a> suggested the existence of an X-linked recessive form of Leigh syndrome on the basis of their observation of affected half brothers (with different fathers), a sex ratio of M1.83:F1.0 in reported cases, and a reported excess of male sibs in reported familial cases. For example, <a href="#33" class="mim-tip-reference" title="Montpetit, V. J., Andermann, F., Carpenter, S. &lt;strong&gt;Subacute necrotizing encephalomyelopathy: a review and a study of two families.&lt;/strong&gt; Brain 94: 1-30, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5552162/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5552162&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/94.1.1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5552162">Montpetit et al. (1971)</a> reported a family in which 2 of 4 brothers were affected; their mother had a brother who died at 2.7 years with spastic quadriplegia and another brother who died at 8 months following a viral illness and convulsions. <a href="#25" class="mim-tip-reference" title="Kissach, A. W., Currie, S., Harriman, D. G., Littlewood, J. M., Payne, R. B., Walker, B. E. &lt;strong&gt;Leigh&#x27;s disease and failure of automatic respiration. (Letter)&lt;/strong&gt; Lancet 304: 662 only, 1974. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4137785/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4137785&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(74)91995-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4137785">Kissach et al. (1974)</a> described 2 affected brothers who had 2 maternal uncles, aged 47 and 49 years, with nystagmus, chorea, and hypercapnia, and, in 1, intermittent coma. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5552162+6891369+4137785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In a male patient with lactic acidosis and decreased pyruvate dehydrogenase E1 activity, <a href="#17" class="mim-tip-reference" title="Endo, H., Hasegawa, K., Narisawa, K., Tada, K., Kagawa, Y., Ohta, S. &lt;strong&gt;Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.&lt;/strong&gt; Am. J. Hum. Genet. 44: 358-364, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2537010/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2537010&lt;/a&gt;]" pmid="2537010">Endo et al. (1989)</a> identified a 4-bp deletion in the PDHA1 cDNA (<a href="/entry/300502#0001">300502.0001</a>). In a female patient with PDH deficiency and decreased levels of the E1-alpha subunit, <a href="#14" class="mim-tip-reference" title="Dahl, H.-H. M., Maragos, C., Brown, R. M., Hansen, L. L., Brown, G. K. &lt;strong&gt;Pyruvate dehydrogenase deficiency caused by deletion of a 7-bp repeat sequence in the E1-alpha gene.&lt;/strong&gt; Am. J. Hum. Genet. 47: 286-293, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2378353/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2378353&lt;/a&gt;]" pmid="2378353">Dahl et al. (1990)</a> identified a 7-bp deletion in the PDHA1 gene (<a href="/entry/300502#0002">300502.0002</a>). The authors noted that the severity of the deficiency in affected females is largely dependent on the X-chromosome inactivation patterns in the brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2537010+2378353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Dahl, H.-H. M., Brown, G. K., Brown, R. M., Hansen, L. L., Kerr, D. S., Wexler, I. D., Patel, M. S., De Meirleir, L., Lissens, W., Chun, K., MacKay, N., Robinson, B. H. &lt;strong&gt;Mutations and polymorphisms in the pyruvate dehydrogenase E1-alpha gene.&lt;/strong&gt; Hum. Mutat. 1: 97-102, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1301207/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1301207&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380010203&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1301207">Dahl et al. (1992)</a> cataloged 20 different mutations, including deletions, insertions, and point mutations. Twelve of the 20 mutations occurred in exons 10 and 11 of this 11-exon gene. Four of the mutations were seen in unrelated patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male infant with PDHAD presenting as acute Leigh syndrome, <a href="#31" class="mim-tip-reference" title="Matthews, P. M., Marchington, D. R., Squier, M., Land, J., Brown, R. M., Brown, G. K. &lt;strong&gt;Molecular genetic characterization of an X-linked form of Leigh&#x27;s syndrome.&lt;/strong&gt; Ann. Neurol. 33: 652-655, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8498846/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8498846&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410330616&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8498846">Matthews et al. (1993)</a> identified a point mutation in the PDHA1 gene (D258A; <a href="/entry/300502#0011">300502.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8498846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of the literature, <a href="#30" class="mim-tip-reference" title="Matthews, P. M., Brown, R. M., Otero, L. J., Marchington, D. R., LeGris, M., Howes, R., Meadows, L. S., Shevell, M., Scriver, C. R., Brown, G. K. &lt;strong&gt;Pyruvate dehydrogenase deficiency: clinical presentation and molecular genetic characterization of five new patients.&lt;/strong&gt; Brain 117: 435-443, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8032855/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8032855&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/117.3.435&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8032855">Matthews et al. (1994)</a> noted that most of the reported mutations in the E1-alpha gene were unique. The sex ratio of PDH E1-alpha deficiency was approximately 1:1, but almost all of the missense mutations had been identified in males and almost all of the deletions or insertions had been found in females. <a href="#30" class="mim-tip-reference" title="Matthews, P. M., Brown, R. M., Otero, L. J., Marchington, D. R., LeGris, M., Howes, R., Meadows, L. S., Shevell, M., Scriver, C. R., Brown, G. K. &lt;strong&gt;Pyruvate dehydrogenase deficiency: clinical presentation and molecular genetic characterization of five new patients.&lt;/strong&gt; Brain 117: 435-443, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8032855/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8032855&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/117.3.435&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8032855">Matthews et al. (1994)</a> speculated that insertions and deletions in hemizygous males may cause intrauterine death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8032855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a boy who presented with Leigh syndrome, <a href="#37" class="mim-tip-reference" title="Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Osaka, H., Kimura, S., Kuroda, Y. &lt;strong&gt;Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 539-548, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9266390/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9266390&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005305614374&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9266390">Naito et al. (1997)</a> identified a mutation in the PDHA1 gene (R263G; <a href="/entry/300502#0022">300502.0022</a>). His unaffected mother was heterozygous for the mutation. Functional studies of cells from the patient and his mother showed decreased affinity of the pyruvate dehydrogenase complex, and the E1 subunit in particular, for thiamine pyrophosphate, a necessary coenzyme. <a href="#37" class="mim-tip-reference" title="Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Osaka, H., Kimura, S., Kuroda, Y. &lt;strong&gt;Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 539-548, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9266390/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9266390&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005305614374&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9266390">Naito et al. (1997)</a> suggested that variable expression of pyruvate dehydrogenase complex deficiencies may depend on surrounding concentrations of thiamine and thiamine pyrophosphate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In monozygotic female twins with PDHAD and differing severity of disease, <a href="#23" class="mim-tip-reference" title="Horga, A., Woodward, C. E., Mills, A., Parees, I., Hargreaves, I. P., Brown, R. M., Bugiardini, E., Brooks, T., Manole, A., Remzova, E., Rahman, S., Reilly, M. M., Houlden, H., Sweeney, M. G., Brown, G. K., Polke, J. M., Gago, F., Parton, M. J., Piteathly, R. D. S., Hanna, M. G. &lt;strong&gt;Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.&lt;/strong&gt; Hum. Genet. 138: 1313-1322, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31673819/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31673819&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=31673819[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-019-02075-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31673819">Horga et al. (2019)</a> identified heterozygosity for a missense mutation (H367L; <a href="/entry/300502#0024">300502.0024</a>) in the PDHA1 gene. In the more severely affected twin (P2), X-inactivation analysis via an androgen receptor assay in peripheral blood showed skewed X inactivation of approximately 75:25, whereas in the less severely affected twin (P1), X inactivation was close to 50:50. PDC activity was reduced in fibroblasts from both sibs, but to a greater extent in P2, and immunocytochemical staining of E1-alpha in patient fibroblasts showed reduced staining in both sibs, with a greater reduction in P2. <a href="#23" class="mim-tip-reference" title="Horga, A., Woodward, C. E., Mills, A., Parees, I., Hargreaves, I. P., Brown, R. M., Bugiardini, E., Brooks, T., Manole, A., Remzova, E., Rahman, S., Reilly, M. M., Houlden, H., Sweeney, M. G., Brown, G. K., Polke, J. M., Gago, F., Parton, M. J., Piteathly, R. D. S., Hanna, M. G. &lt;strong&gt;Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.&lt;/strong&gt; Hum. Genet. 138: 1313-1322, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31673819/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31673819&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=31673819[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-019-02075-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31673819">Horga et al. (2019)</a> concluded that these findings lent support to the hypothesis that the X inactivation pattern affects the phenotypic expression of PDHA1 mutations in heterozygous females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31673819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Blass1971" class="mim-tip-reference" title="Blass, J. P., Kark, R. A. P., Engel, W. K. &lt;strong&gt;Clinical studies of a patient with pyruvate dehydrogenase deficiency.&lt;/strong&gt; Arch. Neurol. 25: 449-460, 1971.">Blass et al. (1971)</a>; <a href="#Brown1989" class="mim-tip-reference" title="Brown, R. M., Dahl, H.-H. M., Brown, G. K. &lt;strong&gt;X-chromosome localization of the functional gene for the E1-alpha subunit of the human pyruvate dehydrogenase complex.&lt;/strong&gt; Genomics 4: 174-181, 1989.">Brown et al. (1989)</a>; <a href="#Duran1985" class="mim-tip-reference" title="Duran, M., Wadman, S. K. &lt;strong&gt;Thiamine-responsive inborn errors of metabolism.&lt;/strong&gt; J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.">Duran and Wadman (1985)</a>; <a href="#Haworth1976" class="mim-tip-reference" title="Haworth, J. C., Perry, T. L., Blass, J. P., Hansen, S., Urguhart, N. &lt;strong&gt;Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.&lt;/strong&gt; Pediatrics 58: 564-572, 1976.">Haworth et al. (1976)</a>; <a href="#Koike1988" class="mim-tip-reference" title="Koike, K., Ohta, S., Urata, Y., Kagawa, Y., Koike, M. &lt;strong&gt;Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase.&lt;/strong&gt; Proc. Nat. Acad. Sci. 85: 41-45, 1988.">Koike et al. (1988)</a>; <a href="#Prick1981" class="mim-tip-reference" title="Prick, M., Gabreels, F., Renier, W., Trijbels, F., Jaspar, H., Lamers, K., Kok, J. &lt;strong&gt;Pyruvate dehydrogenase deficiency restricted to brain.&lt;/strong&gt; Neurology 31: 398-404, 1981.">Prick et al. (1981)</a>; <a href="#Robinson1980" class="mim-tip-reference" title="Robinson, B. H., Taylor, J., Sherwood, W. G. &lt;strong&gt;The genetic heterogeneity of lactic acidosis: occurrence of recognisable inborn errors of metabolism in a pediatric population with lactic acidosis.&lt;/strong&gt; Pediat. Res. 14: 956-962, 1980.">Robinson et al. (1980)</a>; <a href="#Sheu1981" class="mim-tip-reference" title="Sheu, K. R., Hu, C.-W. C., Utter, M. F. &lt;strong&gt;Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts.&lt;/strong&gt; J. Clin. Invest. 67: 1463-1471, 1981.">Sheu et al. (1981)</a>; <a href="#Willems1974" class="mim-tip-reference" title="Willems, J. L., Monnens, L. A. H., Trijbels, J. M. F., Sengers, R. C. A., Veerkamp, J. H. &lt;strong&gt;Pyruvate decarboxylase deficiency in liver. (Letter)&lt;/strong&gt; New Eng. J. Med. 290: 406-407, 1974.">Willems et al. (1974)</a>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Benke1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Benke, P. J., Parker, J. C., Jr., Lubs, M.-L., Benkendorf, J., Feuer, A. E.
<strong>X-linked Leigh's syndrome.</strong>
Hum. Genet. 62: 52-59, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6891369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6891369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6891369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00295603" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Bindoff1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bindoff, L. A., Birch-Machin, M. A., Farnsworth, L., Gardner-Medwin, D., Lindsay, J. G., Turnbull, D. M.
<strong>Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex.</strong>
J. Neurol. Sci. 93: 311-318, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2592988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2592988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2592988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(89)90200-1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Birch-Machin1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Birch-Machin, M. A., Shepherd, I. M., Solomon, M., Yeaman, S. J., Gardner-Medwin, D., Sherratt, H. S. A., Lindsay, J. G., Aynsley-Green, A., Turnbull, D. M.
<strong>Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex.</strong>
J. Inherit. Metab. Dis. 11: 207-217, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799876" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Blass1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Blass, J. P., Avigan, J., Uhlendorf, B. W.
<strong>A defect in pyruvate decarboxylase in a child with an intermittent movement disorder.</strong>
J. Clin. Invest. 49: 423-432, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4313434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4313434</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4313434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI106251" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Blass1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Blass, J. P., Kark, R. A. P., Engel, W. K.
<strong>Clinical studies of a patient with pyruvate dehydrogenase deficiency.</strong>
Arch. Neurol. 25: 449-460, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5110887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5110887</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5110887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1971.00490050083007" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Brown1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, G. K., Haan, E. A., Kirby, D. M., Scholem, R. D., Wraith, J. E., Rogers, J. G., Danks, D. M.
<strong>'Cerebral' lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis.</strong>
Europ. J. Pediat. 147: 10-14, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3123240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3123240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3123240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00442603" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Brown1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M.
<strong>Pyruvate dehydrogenase deficiency.</strong>
J. Med. Genet. 31: 875-879, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7853374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7853374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7853374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.31.11.875" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Brown1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, R. M., Dahl, H.-H. M., Brown, G. K.
<strong>X-chromosome localization of the functional gene for the E1-alpha subunit of the human pyruvate dehydrogenase complex.</strong>
Genomics 4: 174-181, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2737678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2737678</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2737678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0888-7543(89)90297-8" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Brown1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, R. M., Otero, L. J., Brown, G. K.
<strong>Transfection screening for primary defects in the pyruvate dehydrogenase E1-alpha subunit gene.</strong>
Hum. Molec. Genet. 6: 1361-1367, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/6.8.1361" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Brunette1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brunette, M. G., Delvin, E., Hazel, B., Scriver, C. R.
<strong>Thiamine-responsive lactic acidosis in a patient with deficient low-Km pyruvate carboxylase activity in liver.</strong>
Pediatrics 50: 702-711, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4343503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4343503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4343503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Dahl1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dahl, H.-H. M., Brown, G. K., Brown, R. M., Hansen, L. L., Kerr, D. S., Wexler, I. D., Patel, M. S., De Meirleir, L., Lissens, W., Chun, K., MacKay, N., Robinson, B. H.
<strong>Mutations and polymorphisms in the pyruvate dehydrogenase E1-alpha gene.</strong>
Hum. Mutat. 1: 97-102, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.1380010203" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Dahl1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dahl, H.-H. M., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1-alpha subunit.</strong>
Hum. Mutat. 3: 152-155, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8199595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8199595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.1380030210" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Dahl1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dahl, H.-H. M., Hansen, L. L., Brown, R. M., Danks, D. M., Rogers, J. G., Brown, G. K.
<strong>X-linked pyruvate dehydrogenase E1-alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.</strong>
J. Inherit. Metab. Dis. 15: 835-847, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1293379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1293379</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1293379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01800219" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Dahl1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dahl, H.-H. M., Maragos, C., Brown, R. M., Hansen, L. L., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency caused by deletion of a 7-bp repeat sequence in the E1-alpha gene.</strong>
Am. J. Hum. Genet. 47: 286-293, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2378353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2378353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2378353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="de Meirleir1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
de Meirleir, L., Specola, N., Seneca, S., Lissens, W.
<strong>Pyruvate dehydrogenase E1-alpha deficiency in a family: different clinical presentation in two siblings.</strong>
J. Inherit. Metab. Dis. 21: 224-226, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686362</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9686362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1005347501111" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Duran1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3930844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3930844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3930844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01800663" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Endo1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Endo, H., Hasegawa, K., Narisawa, K., Tada, K., Kagawa, Y., Ohta, S.
<strong>Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.</strong>
Am. J. Hum. Genet. 44: 358-364, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2537010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2537010</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2537010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Evans1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Evans, O. B.
<strong>Episodic weakness in pyruvate decarboxylase deficiency.</strong>
J. Pediat. 105: 961-963, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6502351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6502351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6502351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(84)80090-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Falk1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Falk, R. E., Cederbaum, S. D., Blass, J. P., Gibson, G. E., Kark, R. A. P., Carrel, R. E.
<strong>Ketonic diet in the management of pyruvate dehydrogenase deficiency.</strong>
Pediatrics 58: 713-721, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/824610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">824610</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=824610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Farrell1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Farrell, D. F., Clark, A. F., Scott, C. R., Wennberg, R. P.
<strong>Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.</strong>
Science 187: 1082-1084, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/803713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">803713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=803713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.803713" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Fouque2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fouque, F., Brivet, M., Boutron, A., Vequaud, C., Marsac, C., Zabot, M.-T., Benelli, C.
<strong>Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency.</strong>
Pediat. Res. 53: 793-799, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12621116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12621116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12621116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/01.PDR.0000057987.46622.64" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Haworth1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Haworth, J. C., Perry, T. L., Blass, J. P., Hansen, S., Urguhart, N.
<strong>Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.</strong>
Pediatrics 58: 564-572, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/184426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">184426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=184426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Horga2019" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Horga, A., Woodward, C. E., Mills, A., Parees, I., Hargreaves, I. P., Brown, R. M., Bugiardini, E., Brooks, T., Manole, A., Remzova, E., Rahman, S., Reilly, M. M., Houlden, H., Sweeney, M. G., Brown, G. K., Polke, J. M., Gago, F., Parton, M. J., Piteathly, R. D. S., Hanna, M. G.
<strong>Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.</strong>
Hum. Genet. 138: 1313-1322, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31673819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31673819</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31673819[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31673819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s00439-019-02075-9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Kerr1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S.
<strong>A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.</strong>
Pediat. Res. 24: 95-100, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3137520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3137520</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3137520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-198807000-00022" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Kissach1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kissach, A. W., Currie, S., Harriman, D. G., Littlewood, J. M., Payne, R. B., Walker, B. E.
<strong>Leigh's disease and failure of automatic respiration. (Letter)</strong>
Lancet 304: 662 only, 1974. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4137785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4137785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4137785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(74)91995-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Koike1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Koike, K., Ohta, S., Urata, Y., Kagawa, Y., Koike, M.
<strong>Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase.</strong>
Proc. Nat. Acad. Sci. 85: 41-45, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3422424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3422424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3422424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.85.1.41" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Lissens1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lissens, W., Vreken, P., Barth, P. G., Wijburg, F. A., Ruitenbeek, W., Wanders, R. J. A., Seneca, S., Liebaers, I., De Meirleir, L.
<strong>Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1-alpha gene.</strong>
Europ. J. Pediat. 158: 853-857, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10486093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10486093</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10486093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s004310051222" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Livingstone1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Livingstone, I. R., Gardner-Medwin, D., Pennington, R. J. T.
<strong>Familial intermittent ataxia with possible X-linked recessive inheritance: two patients with abnormal pyruvate metabolism and a response to acetazolamide.</strong>
J. Neurol. Sci. 64: 89-97, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6539810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6539810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6539810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(84)90059-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Lonsdale1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lonsdale, D., Faulkner, W. R., Price, J. M., Smeby, R. R.
<strong>Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperphenylalaninemia and hyperalaninuria.</strong>
Pediatrics 43: 1025-1034, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5786203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5786203</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5786203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Matthews1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matthews, P. M., Brown, R. M., Otero, L. J., Marchington, D. R., LeGris, M., Howes, R., Meadows, L. S., Shevell, M., Scriver, C. R., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency: clinical presentation and molecular genetic characterization of five new patients.</strong>
Brain 117: 435-443, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8032855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8032855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8032855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/117.3.435" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Matthews1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matthews, P. M., Marchington, D. R., Squier, M., Land, J., Brown, R. M., Brown, G. K.
<strong>Molecular genetic characterization of an X-linked form of Leigh's syndrome.</strong>
Ann. Neurol. 33: 652-655, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8498846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8498846</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8498846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.410330616" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="McCormick1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McCormick, K., Viscardi, R. M., Robinson, B., Heininger, J.
<strong>Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate.</strong>
Am. J. Med. Genet. 22: 291-299, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4050860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4050860</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4050860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320220211" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Montpetit1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Montpetit, V. J., Andermann, F., Carpenter, S.
<strong>Subacute necrotizing encephalomyelopathy: a review and a study of two families.</strong>
Brain 94: 1-30, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5552162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5552162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5552162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/94.1.1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Naito1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naito, E., Ito, M., Takeda, E., Yokota, I., Yoshijima, S., Kuroda, Y.
<strong>Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.</strong>
Pediat. Res. 36: 340-346, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7808831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7808831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7808831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-199409000-00013" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Naito1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Kuroda, Y.
<strong>Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex.</strong>
Europ. J. Pediat. 157: 648-652, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9727848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9727848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9727848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s004310050903" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Naito2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Ogawa, Y., Kitamura, S., Takada, E., Horii, Y., Kuroda, Y.
<strong>Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region.</strong>
Biochim. Biophys. Acta 1588: 79-84, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12379317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12379317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12379317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0925-4439(02)00142-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Naito1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Osaka, H., Kimura, S., Kuroda, Y.
<strong>Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.</strong>
J. Inherit. Metab. Dis. 20: 539-548, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1005305614374" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Okajima2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Okajima, K., Warman, M. L., Byrne, L. C., Kerr, D. S.
<strong>Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype.</strong>
Molec. Genet. Metab. 87: 162-168, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16412675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16412675</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16412675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2005.09.023" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Pirot2016" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pirot, N., Crahes, M., Adle-Biassette, H., Soares, A., Bucourt, M., Boutron, A., Carbillon, L., Mignot, C., Trestard, L., Bekri, S., Laquerriere, A.
<strong>Phenotypic and neuropathological characterization of fetal pyruvate dehydrogenase deficiency.</strong>
J. Neuropath. Exp. Neurol. 75: 227-238, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26865159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26865159</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26865159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/jnen/nlv022" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Prick1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Prick, M., Gabreels, F., Renier, W., Trijbels, F., Jaspar, H., Lamers, K., Kok, J.
<strong>Pyruvate dehydrogenase deficiency restricted to brain.</strong>
Neurology 31: 398-404, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6783978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6783978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6783978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.31.4.398" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Robinson1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robinson, B. H., MacMillan, H., Petrova-Benedict, R., Sherwood, W. G.
<strong>Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex.</strong>
J. Pediat. 111: 525-533, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3116190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3116190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3116190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(87)80112-9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Robinson1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robinson, B. H., Sherwood, W. G.
<strong>Lactic acidaemia.</strong>
J. Inherit. Metab. Dis. 7: 69-73, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6434848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6434848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6434848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF03047378" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Robinson1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robinson, B. H., Taylor, J., Sherwood, W. G.
<strong>The genetic heterogeneity of lactic acidosis: occurrence of recognisable inborn errors of metabolism in a pediatric population with lactic acidosis.</strong>
Pediat. Res. 14: 956-962, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6775276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6775276</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6775276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-198008000-00013" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Sheu1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sheu, K. R., Hu, C.-W. C., Utter, M. F.
<strong>Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts.</strong>
J. Clin. Invest. 67: 1463-1471, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6262377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6262377</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6262377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/jci110176" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Shevell1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shevell, M. I., Matthews, P. M., Scriver, C. R., Brown, R. M., Otero, L. J., Legris, M., Brown, G. K., Arnold, D. L.
<strong>Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency.</strong>
Pediat. Neurol. 11: 224-229, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7880337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7880337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7880337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0887-8994(94)90107-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="Stromme1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Stromme, J. H., Borud, O., Moe, P. J.
<strong>Fatal lactic acidosis in a newborn attributable to a congenital defect of pyruvate dehydrogenase.</strong>
Pediat. Res. 10: 62-66, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/813176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">813176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=813176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-197601000-00012" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Takakubo1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Takakubo, F., Cartwright, P., Hoogenraad, N., Thorburn, D. R., Collins, F., Lithgow, T., Dahl, H.-H. M.
<strong>An amino acid substitution in the pyruvate dehydrogenase E1-alpha gene, affecting mitochondrial import of the precursor protein.</strong>
Am. J. Hum. Genet. 57: 772-780, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Wexler1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wexler, I. D., Hemalatha, S. G., Liu, T.-C., Berry, S. A., Kerr, D. S., Patel, M. S.
<strong>A mutation in the E1-alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency.</strong>
Pediat. Res. 32: 169-174, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1508605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1508605</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1508605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-199208000-00009" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Wexler1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wexler, I. D., Kerr, D. S., Ho, L., Lusk, M. M., Pepin, R. A., Javed, A. A., Mole, J. E., Jesse, B. W., Thekkumkara, T. J., Pons, G., Patel, M. S.
<strong>Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.</strong>
Proc. Nat. Acad. Sci. 85: 7336-7340, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3140238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3140238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3140238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.85.19.7336" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Wick1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wick, H., Schweizer, K., Baumgartner, R.
<strong>Thiamine dependency in a patient with congenital lacticacidaemia due to pyruvate dehydrogenase deficiency.</strong>
Agents Actions 7: 405-410, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/413346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">413346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=413346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01969575" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Wicking1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wicking, C. A., Brown, G. K., Scholem, R. D., Hunt, S. M., Dahl, H.-H. M.
<strong>Molecular analysis of pyruvate dehydrogenase deficiency. (Abstract)</strong>
Am. J. Hum. Genet. 37: A182 only, 1985.
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Willems1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Willems, J. L., Monnens, L. A. H., Trijbels, J. M. F., Sengers, R. C. A., Veerkamp, J. H.
<strong>Pyruvate decarboxylase deficiency in liver. (Letter)</strong>
New Eng. J. Med. 290: 406-407, 1974.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4810126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4810126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4810126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 01/12/2021
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 09/21/2020<br>Cassandra L. Kniffin - updated : 10/28/2014<br>Cassandra L. Kniffin - updated : 1/4/2010<br>Victor A. McKusick - updated : 7/14/2004<br>Cassandra L. Kniffin - reorganized : 7/14/2004<br>Cassandra L. Kniffin - updated : 7/9/2004
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin : 7/6/2004
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 08/08/2023
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 01/13/2021<br>carol : 01/12/2021<br>carol : 09/21/2020<br>carol : 08/03/2020<br>alopez : 05/15/2019<br>carol : 02/09/2018<br>carol : 08/17/2017<br>carol : 11/03/2014<br>mcolton : 10/29/2014<br>ckniffin : 10/28/2014<br>carol : 2/3/2012<br>ckniffin : 2/1/2012<br>ckniffin : 1/31/2012<br>carol : 7/22/2011<br>terry : 4/21/2011<br>wwang : 2/16/2010<br>ckniffin : 1/4/2010<br>wwang : 12/6/2005<br>ckniffin : 12/2/2005<br>alopez : 6/13/2005<br>terry : 3/3/2005<br>terry : 2/10/2005<br>tkritzer : 7/23/2004<br>tkritzer : 7/19/2004<br>ckniffin : 7/15/2004<br>terry : 7/14/2004<br>carol : 7/14/2004<br>ckniffin : 7/9/2004
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 312170
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY; PDHAD
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY<br />
PYRUVATE DECARBOXYLASE DEFICIENCY<br />
ATAXIA, INTERMITTENT, WITH ABNORMAL PYRUVATE METABOLISM<br />
PDH DEFICIENCY<br />
ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY<br />
ATAXIA WITH LACTIC ACIDOSIS I
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
LACTIC ACIDEMIA, THIAMINE-RESPONSIVE, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 124593001, 46683007; &nbsp;
<strong>ICD10CM:</strong> E74.4; &nbsp;
<strong>ORPHA:</strong> 765, 79243; &nbsp;
<strong>DO:</strong> 3649; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
Xp22.12
</span>
</td>
<td>
<span class="mim-font">
Pyruvate dehydrogenase E1-alpha deficiency
</span>
</td>
<td>
<span class="mim-font">
312170
</span>
</td>
<td>
<span class="mim-font">
X-linked dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
PDHA1
</span>
</td>
<td>
<span class="mim-font">
300502
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because pyruvate dehydrogenase E1-alpha deficiency (PDHAD) is caused by mutation in the gene encoding the E1-alpha polypeptide (PDHA1; 300502) of the pyruvate dehydrogenase (PDH) complex, which maps to chromosome Xp22.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). </p><p><strong><em>Genetic Heterogeneity of Pyruvate Dehydrogenase Complex Deficiency</em></strong></p><p>
PDH deficiency can also be caused by mutation in other subunits of the PDH complex, including a form (PDHXD; 245349) caused by mutation in the component X gene (PDHX; 608769) on chromosome 11p13; a form (PDHBD; 614111) caused by mutation in the PDHB gene (179060) on chromosome 3p14; a form (PDHDD; 245348) caused by mutation in the DLAT gene (608770) on chromosome 11q23; a form (PDHPD; 608782) caused by mutation in the PDP1 gene (605993) on chromosome 8q22; and a form (PDHLD; 614462) caused by mutation in the LIAS gene (607031) on chromosome 4p14.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In general, there are 2 major presentations of PDH deficiency, metabolic and neurologic, which occur at equal frequency. The metabolic form presents as severe lactic acidosis in the newborn period, usually leading to death. Patients with the neurologic presentation are hypotonic and lethargic, and develop seizures, mental retardation, and spasticity. They often have structural abnormalities in the central nervous system with minimal or absent metabolic abnormalities. Between these 2 extremes, there is a continuous spectrum of intermediate forms characterized by intermittent episodes of lactic acidosis associated with cerebellar ataxia. Many patients fit into the category of Leigh syndrome (see 256000) (Brown et al., 1994). </p><p>Blass et al. (1970) reported deficiency of pyruvate decarboxylase in an 8-year-old boy who had suffered 2 to 6 episodes of ataxia each year since the age of 16 months. Most attacks followed nonspecific febrile illness or other stresses. Choreoathetosis and cerebellar ataxia were present during the episodes, with mild clumsiness between episodes. Laboratory studies showed increased blood pyruvic acid, increased blood alanine, and a decreased activity of pyruvate decarboxylase (20% of normal). The father's fibroblasts and leukocytes showed partially defective pyruvate decarboxylase, and values in the mother were at the lower limit of normal. The patient of Blass et al. (1970) was reminiscent of a boy reported by Lonsdale et al. (1969) with intermittent ataxia and choreoathetosis precipitated by acute infections. Both patients showed conspicuous abnormalities of eye movement as in Wernicke-Korsakoff syndrome (277730). Thiamine in large doses appeared to benefit Lonsdale's patient. </p><p>Farrell et al. (1975) reported a 6-month-old infant with fatal congenital lactic acidosis and deficiency of pyruvate decarboxylase. Stromme et al. (1976) reported an infant with increased blood lactate, alanine, and serine. Fibroblasts cultured from skin showed a severe decrease in activity of the PDH complex (8% of normal) and the first enzyme of the complex (4% of normal). </p><p>Livingstone et al. (1984) described a family in which 5 males in 3 sibships had intermittent cerebellar ataxia and biochemical features of abnormal pyruvate metabolism. The patients were related through 3 presumed carrier females. Postmortem examination of 1 of the affected males, who died at age 50, showed neuropathologic findings suggestive of Leigh syndrome. There was cerebellar degeneration with a distribution suggestive of olivopontocerebellar atrophy, but the histologic appearance in tissues around the third ventricle and aqueduct was similar to those seen in Wernicke encephalopathy and in Leigh syndrome. There was no response to administration of thiamine. One of the affected males had recurrent episodes of ataxia and dysarthria beginning at the age of 3 years. Each attack lasted from 2 to 12 days and occurred every 3 to 4 months. Episodes were less severe and less frequent after the age of 14 years, and he was able to hold down a steady job as a laborer. In a teenaged affected male, elevated levels of fasting serum lactate and pyruvate were noted during recovery from a typical attack. At 10 years of age, his IQ was 65. One male died of pneumonia at the age of 5 years after recurrent attacks of hyperventilation and unsteadiness from the age of 3 years. Livingstone et al. (1984) observed at least a temporary favorable response to acetazolamide, and suggested that the basic defect might reside in the gene for the E1-alpha component of the pyruvate dehydrogenase complex. </p><p>Robinson and Sherwood (1984) found that 18 of 23 patients with congenital lactic acidemia had a defect in the first component of the PDH complex. Ten cases had facial dysmorphism consisting of a narrow head, broad nasal bridge and flared nostrils, and microcephaly. Two patients had agenesis of the corpus callosum. In a study of 30 patients with defect in the PDH complex E1 component Robinson et al. (1987) found that residual activity of the PDH complex ranged from 1.6% to 69.5% of controls. Seven patients died before 6 months of age, and another 5 before 2 years of age. Sixteen of the surviving patients and the 5 who died before age 2 had psychomotor retardation, and 17 children had structural damage of the central nervous system, ranging from cerebral atrophy to cystic lesions in the cortex, basal ganglia, and brainstem resembling Leigh syndrome. </p><p>Evans (1984) reported episodic weakness in pyruvate decarboxylase deficiency. Brown et al. (1988) reported 6 patients with early onset of neurologic symptoms, gross cerebral changes, and increased levels of pyruvate and lactate in cerebrospinal fluid. Although the patients appeared to have a defect in pyruvate metabolism as evidenced by deficient pyruvate dehydrogenase activity in cultured fibroblasts, systemic acidosis was not a problem clinically and blood pyruvate and lactate concentrations were only slightly raised. Brown et al. (1988) termed this form of the disorder 'cerebral' lactic acidosis. </p><p>Kerr et al. (1988) described 2 brothers who had E1 deficiency in liver, skeletal muscle, and heart. The pyruvate dehydrogenase complex showed about 30% activity in kidney. The second (E2) and third (E3) components of the complex were normal. PDH activity was less than 10% of controls in lymphocytes, but normal in skin fibroblasts. Kerr et al. (1988) considered the possibility of X-linked inheritance because these patients and 4 other similarly affected patients with absence of both E1 subunits were male and because the mother, but not the father, had reduced enzyme activity in her lymphocytes. The fact that the maternal grandmother and great-grandmother had normal lymphocyte pyruvate dehydrogenase activity suggested that the mutation had originated with the mother of the brothers. The clinical course was as severe as in the usual cases, but the neuropathologic findings of Leigh syndrome were not found. Kerr et al. (1988) noted that if the activity of pyruvate dehydrogenase had not been found to be very low in lymphocytes, the defect could easily have been overlooked because of the normal activity in fibroblasts. In the patients reported by Kerr et al. (1988), Wexler et al. (1992) identified a mutation in the PDHA1 gene (300502.0008). </p><p>Matthews et al. (1993) reported an infant with a clinical diagnosis of Leigh syndrome. He was delivered by cesarean section at 36 weeks because of worsening preeclampsia and a breech presentation, and was limp and apneic on delivery. He showed little growth or development and died at about 13 weeks. Pathologic findings were consistent with subacute necrotizing encephalomyelopathy, and deficiency of the pyruvate dehydrogenase complex was demonstrated enzymatically. </p><p>Dahl and Brown (1994) described a male infant with E1-alpha deficiency who died suddenly at the age of 18 months after becoming acutely ill with an intercurrent viral illness. Marked spongiform change was found in the globus pallidus and less extensive degenerative change in the dentate nucleus and surrounding white matter. He had previously been found to have developmental delay and biochemical evidence of compensated metabolic acidosis with mild elevation of the blood lactate and pyruvate concentrations. A mutation was identified in the PDHA1 gene (300502.0012). </p><p>Takakubo et al. (1995) reported a 10-month-old male with E1-alpha deficiency who presented with intermittent divergent squint. A half brother had died at age 33 months with autopsy-confirmed Leigh syndrome after a progressive neurologic illness that began with ocular symptoms. No other neurologic abnormalities were found in the proband, and blood lactate and pyruvate levels were within normal limits. However, cerebrospinal fluid lactate and pyruvate levels were markedly raised, and cultured skin fibroblasts showed PDH complex activity of 28% and PDHA1 activity of 23% of normal control mean. A mutation in the PDHA1 gene (300502.0017) was found in the proband, an affected brother, and the mildly affected mother. </p><p>Naito et al. (1997) reported a boy with PDHAD who was born at term to healthy consanguineous parents. At age 4 months, he showed developmental delay. He had increased blood lactate and pyruvate as well as basal ganglia lesions on MRI, consistent with Leigh syndrome. His older brother had shown a similar disorder, with hypotonia, mental retardation, lactic acidemia, and basal ganglia lesions. The brothers died at ages 6 and 4 years from respiratory failure. The index patient showed some clinical improvement with thiamine therapy. </p><p>De Meirleir et al. (1998) reported a 3-year-old boy and a younger sister with E1-alpha deficiency caused by mutation in the PDHA1 gene (300502.0019). The boy showed general hypotonia during development, and from the age of 3 months had several episodes of ptosis lasting 1 to 2 days. These episodes became more frequent between 15 and 17 months of age and were associated with swallowing disturbances and hypotonia, paralysis of lateral gaze, and tachypnea. Metabolic acidosis was found. He had 2 episodes of acute ataxia with weakness between the ages 2 and 3 years. MRI of the brain demonstrated bilateral pallidal lesions and demyelinating pons lesions. The more severely affected younger sister presented from birth with severe hypotonia and dysmorphia and by the age of 10 months developed spastic quadriplegia with areflexia and severe mental retardation. </p><p>Okajima et al. (2006) reported a 7-year-old boy with E1-alpha deficiency resulting from somatic mosaicism for a splice site mutation in the PDHA1 gene. The diagnosis was difficult due to the relatively mild and nonspecific features. He presented at age 6 months with moderately delayed motor development and was subsequently found to have intermittent elevated blood lactate on several occasions. Other biochemical studies and brain MRI were normal. At 18 months, he had mild microcephaly, mild global developmental delay, central hypotonia, and mild spasticity of the lower extremities. He spoke his first words at 14 months and walked at 24 months. Repeat measurements showed increased CSF lactate and pyruvate, and the correct diagnosis was made. At age 6 years, he had cognitive impairment, showed some repetitive automatisms, poor attention span, hyperactivity, and mild hypotonia. Total PDC activity was significantly decreased in fibroblasts and skeletal muscle, but normal in lymphocytes. Detailed genetic, biochemical, and Western blot analysis of buccal cells, hair, lymphoblasts, and fibroblasts showed a mixed species of mutant and normal E1-alpha, with corresponding variable activity and immunoreactivity, all consistent with somatic mosaicism. </p><p><strong><em>Heterozygous Females</em></strong></p><p>
Dahl et al. (1992) described 3 female patients with pyruvate dehydrogenase deficiency due to mutation in the PDHA1 gene (300502.0009). Two of the patients demonstrated typical features of the disorder with severe neurologic dysfunction, degenerative changes, and developmental anomalies in the brain, together with variable lactic acidosis. Both had manifestations from early after birth; 1 died at 5 months and the other at 17 years. The third patient, an adult who was the mother of the 17-year-old, had delayed development. She did not walk until 4 years of age and could not spell until she was 20. She had epilepsy which was reasonably controlled with medication. The mother had 4 brothers, all of normal intelligence. Dahl et al. (1992) suggested that she may have been a mosaic for an early somatic mutation. </p><p>Matthews et al. (1994) reported 2 female patients with early-onset encephalopathy and lactic acidosis who had PDH activity in the normal range. One had mild dysmorphic features including downslanting palpebral fissures, a broad philtrum, and microcephaly. There was generalized brain atrophy, ventriculomegaly, and a frontoparietal cystic lesion. The X-inactivation pattern in the fibroblasts was 80 to 20. This was the third child of consanguineous parents; a previous male infant had died with severe developmental delay and lactic acidosis. The second patient was hypotonic with marked developmental delay, cerebral atrophy, and extensor infantile spasms at 2 months of age. X-inactivation pattern was 70 to 30. The authors noted that PDH activity was well within the normal range in both girls and the diagnosis was only possible by DNA studies, which identified mutations in the PDHA1 gene (300502.0015; 300502.0016). </p><p>Shevell et al. (1994) described 3 infant girls with PDH complex deficiency. MRI revealed hypoplasia, particularly of the posterior part of the corpus callosum, as well as global white matter loss without heterotopias. Phosphorus magnetic resonance spectroscopy (MRS) of muscle revealed abnormally low phosphorylation potentials. Proton MRS of the brain demonstrated a large increase in signals of lactic acid and decrease of the relative signal intensity of N-acetylaspartate. The authors proposed that cerebral dysgenesis and cerebral lactic acidemia should suggest PDH complex deficiency. </p><p>Lissens et al. (1999) reported 2 unrelated girls with PDH deficiency caused by 2 different mutations in the PDHA1 gene (300502.0020; 300502.0021). Both patients had spastic quadriplegia, severe mental retardation, and microcephaly. One patient presented at the age of 5 months with infantile spasms. Lactate levels in blood and cerebrospinal fluid were increased, with a normal lactate/pyruvate ratio. Brain MRI at the age of 13 years revealed asymmetric irregular ventricular enlargement, abnormally steep angle of the Sylvian fissures, normal myelination, an intact corpus callosum, and a normal-sized cerebellum. In the second patient, MRI of the brain showed cortical atrophy of both cerebral hemispheres and cerebellum, a partial agenesis of the corpus callosum, and dilatation of the lateral and third ventricles. Both patients had low PDH activity, but normal amounts of all subunits on Western blotting. Blood lactate and pyruvate levels were increased, with a normal lactate/pyruvate ratio. X-inactivation studies in fibroblast DNA showed that the second patient had an almost completely skewed inactivation pattern. </p><p>Pirot et al. (2016) reported 2 unrelated female fetuses (patients 1 and 2) and a 7-year-old sister of patient 2 with PDHAD. Patient 1 was found to have partial agenesis of the corpus callosum and microcephaly on routine prenatal ultrasound at 22 weeks' gestation. MRI at 27 weeks and 6 days' gestation showed agenesis of the corpus callosum, microcephaly, colpocephaly, delayed gyral formation, cerebellar hypoplasia, and microcavitary periventricular white matter lesions. Examination after pregnancy termination at 30 weeks' gestation showed dysmorphic features, including frontal bossing, smooth philtrum, a thin upper lip, low-set ears, and retrognathia. Macroscopic and histologic examination of the brain showed pachygyria, polymicrogyria, ventricular dilation, pseudocysts of the subependymal germinal matrix, and basal ganglia microcalcifications. Patient 2 was found to have agenesis of the corpus callosum, mild ventricular dilation, and delayed gyration with opercular dysplasia of the Sylvian fissure on ultrasound at 22 weeks' gestation. On ultrasound at 28 weeks' gestation, abnormal gyration and cerebellar hypoplasia were also suspected. Examination after pregnancy termination at 29 weeks' gestation showed extensive subcortical cavitary lesions in the brain, corpus callosum hypoplasia, pseudocysts of the subependymal germinal matrix, dilation of the ventricles, reactive gliosis, and ischemic lesions. Her 7-year-old sister, born several years later, had microcephaly, hypotonia, Pierre Robin sequence, and brainstem dysfunction at birth. She had dysmorphic features, including a flat forehead, long and smooth philtrum, and a thin upper lip. Brain MRI at 1 month of age showed bilateral paraventricular pseudocysts and corpus callosum hypoplasia with posterior agenesis. At age 7 years, she was described as severely handicapped. </p><p>Horga et al. (2019) reported monozygotic female twins with PDH deficiency who had differing X-inactivation patterns and severity of disease. The sibs were born at 31 weeks' gestation due to maternal preeclampsia and were discharged from the neonatal unit after 6 weeks. They were found to have mild global developmental delay. Ten days after receiving vaccinations at 15 months of age, both became febrile and hypotonic and lost developmental milestones, which were subsequently regained. Both sibs were diagnosed with Leigh syndrome at 5 years of age based on increased CSF lactate and brain MRIs showing signal changes in the globi pallidi and peritrigonal white matter. The more severely affected sib (P2) had skewed X inactivation. She continued to have episodes of encephalopathy triggered by infections, and she developed dysarthria, dysmetria, dystonic posturing of upper limbs, and pyramidal tract signs in the lower limbs. In adolescence she developed a seizure disorder, and subsequently developed behavioral changes and deterioration of motor function. The less severely affected sib (P1), who did not have skewed X inactivation, had 2 subsequent episodes of encephalopathy at ages 14 and 19 years in the context of acute infection, from which she recovered. She developed seizures in her teenaged years, and had mild learning difficulties and memory problems. At 29 years of age, she had moderate dysarthria, increased tone in her lower limbs, and tremor of the upper limbs. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>With a polyclonal antibody, Wicking et al. (1985) identified absence of the E1 alpha-subunit in a patient with severe neonatal lactic acidosis and structural alteration of the E1 protein in another patient with severe brain damage associated with less severe lactic acidosis. Birch-Machin et al. (1988) described an infant with severe pyruvate dehydrogenase deficiency who had low concentrations of both the alpha and beta subunits of E1 in immunochemical studies of liver and skeletal muscle mitochondrial fractions. </p><p>Using both specific antibodies to pyruvate dehydrogenase and cDNAs coding for its 2 alpha and beta subunits, Wexler et al. (1988) characterized 11 patients with PDH deficiency. Three different patterns were found: 7 patients had immunologically detectable cross-reactive material for the alpha and beta proteins of PDH; 2 patients had no detectable cross-reactive protein for either subunit, but had normal amounts of mRNA for both subunits; and 2 patients had no detectable cross-reactive proteins with diminished amounts of the alpha subunit mRNA only. The results indicated that loss of PDH activity may be associated with either absent or catalytically inactive proteins or with decreased mRNA. When mRNA for 1 of the subunits is lacking, both protein subunits are absent, suggesting that a mutation affecting the expression of one of them causes the remaining uncomplexed subunit to be unstable. </p><p>In a patient with intermittent ataxia, a disorder of pyruvate metabolism, and an X-linked pattern of inheritance, Bindoff et al. (1989) found immunochemical evidence for E1 deficiency in skeletal muscle mitochondria. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Brown et al. (1994) reviewed all aspects of PDH deficiency, including prenatal diagnosis and treatment. They noted that the biochemical abnormalities may be minimal and easily overlooked, especially when the patient has extensive structural defects in the brain. The variable manifestations of the disorder in heterozygous females is largely determined by differences in the pattern of X inactivation, and there are considerable difficulties in establishing the diagnosis when it is based on measurements of enzyme activity and immunoreactive protein. </p><p>In a significant number of patients with biochemical evidence of a defect in the E1-alpha component of the pyruvate dehydrogenase complex, it is not possible to identify a mutation in the gene coding regions. Brown et al. (1997) developed a method to screen for E1-alpha gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the PDHA1 gene showed restoration of enzyme activity. A number of patients were identified in whom deficient enzyme activity was not restored by expression of the normal cDNA, indicating that an alternative explanation for the enzyme defect must be sought. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Falk et al. (1976) reported successful treatment of PDH deficiency with a ketogenic diet. </p><p>McCormick et al. (1985) reported the successful use of sodium benzoate in a neonate with hyperammonemia associated with congenital lactic acidosis caused by a partial deficiency of the E1 component of the PDH complex. The authors noted that this biochemical disturbance had not previously been observed in PDH deficiency. </p><p>Fouque et al. (2003) investigated the underlying mechanism for the differential response to dichloroacetate (DCA), a structural pyruvate analog, in fibroblasts from 3 PDHC-deficient patients with very low levels of PDHC activity, unstable polypeptides, and different mutations in the E1-alpha subunit: 2 point mutations and a deletion mutation. Cell lines with the point mutations responded to treatment, whereas the cell line with the deletion did not. Fouque et al. (2003) concluded that mutations that retain catalytic activity may be DCA responsive due to increased E1-alpha subunit stability and that DCA may be useful as an adjunct to ketogenic and thiamine treatment. </p><p><strong><em>Thiamine-Responsive Pyruvate Dehydrogenase Deficiency</em></strong></p><p>
Lonsdale et al. (1969), Brunette et al. (1972), and Wick et al. (1977) reported patients who benefited from thiamine. </p><p>Naito et al. (1994) reported a patient with thiamine-responsive deficiency of the PDH complex, resulting from a reduced affinity of the PDHC for thiamine pyrophosphate (TPP). Naito et al. (1998) reported on the characteristics of 13 patients with thiamine-responsive lactic acidemia and examined the activity of the PDH complex to sodium dichloroacetate (DCA), known as an activator of PDHC. Three groups were identified according to PDHC activity in cell culture: 2 patients had very low PDHC activity, which was not increased by DCA but was increased at high TPP concentrations; 5 patients displayed below normal PDHC activity, which was increased by DCA and by high TPP concentrations; and 6 patients had normal PDHC activity at low and high TPP concentrations, which was increased by DCA. The authors concluded that PDHC deficiency in the patients of the first 2 groups was due to a decreased affinity of PDHC for TPP. </p><p>Naito et al. (2002) reported 2 unrelated male patients with thiamine-responsive E1-alpha deficiency. Both boys had onset of weakness, hypotonia, and gait instability at an early age, and had mutations in the PDHA1 gene (300502.0012 and 300502.0023). Analysis of cultured lymphoblastoid cells from the patients showed a decrease in E1 affinity for TPP and a significant increase in PDH complex and E1 activity in response to high TPP concentrations. With thiamine therapy, both patients showed clinical improvement in blood lactate and pyruvate concentrations and in neurologic symptoms. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Benke et al. (1982) suggested the existence of an X-linked recessive form of Leigh syndrome on the basis of their observation of affected half brothers (with different fathers), a sex ratio of M1.83:F1.0 in reported cases, and a reported excess of male sibs in reported familial cases. For example, Montpetit et al. (1971) reported a family in which 2 of 4 brothers were affected; their mother had a brother who died at 2.7 years with spastic quadriplegia and another brother who died at 8 months following a viral illness and convulsions. Kissach et al. (1974) described 2 affected brothers who had 2 maternal uncles, aged 47 and 49 years, with nystagmus, chorea, and hypercapnia, and, in 1, intermittent coma. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a male patient with lactic acidosis and decreased pyruvate dehydrogenase E1 activity, Endo et al. (1989) identified a 4-bp deletion in the PDHA1 cDNA (300502.0001). In a female patient with PDH deficiency and decreased levels of the E1-alpha subunit, Dahl et al. (1990) identified a 7-bp deletion in the PDHA1 gene (300502.0002). The authors noted that the severity of the deficiency in affected females is largely dependent on the X-chromosome inactivation patterns in the brain. </p><p>Dahl et al. (1992) cataloged 20 different mutations, including deletions, insertions, and point mutations. Twelve of the 20 mutations occurred in exons 10 and 11 of this 11-exon gene. Four of the mutations were seen in unrelated patients. </p><p>In a male infant with PDHAD presenting as acute Leigh syndrome, Matthews et al. (1993) identified a point mutation in the PDHA1 gene (D258A; 300502.0011). </p><p>In a review of the literature, Matthews et al. (1994) noted that most of the reported mutations in the E1-alpha gene were unique. The sex ratio of PDH E1-alpha deficiency was approximately 1:1, but almost all of the missense mutations had been identified in males and almost all of the deletions or insertions had been found in females. Matthews et al. (1994) speculated that insertions and deletions in hemizygous males may cause intrauterine death. </p><p>In a boy who presented with Leigh syndrome, Naito et al. (1997) identified a mutation in the PDHA1 gene (R263G; 300502.0022). His unaffected mother was heterozygous for the mutation. Functional studies of cells from the patient and his mother showed decreased affinity of the pyruvate dehydrogenase complex, and the E1 subunit in particular, for thiamine pyrophosphate, a necessary coenzyme. Naito et al. (1997) suggested that variable expression of pyruvate dehydrogenase complex deficiencies may depend on surrounding concentrations of thiamine and thiamine pyrophosphate. </p><p>In monozygotic female twins with PDHAD and differing severity of disease, Horga et al. (2019) identified heterozygosity for a missense mutation (H367L; 300502.0024) in the PDHA1 gene. In the more severely affected twin (P2), X-inactivation analysis via an androgen receptor assay in peripheral blood showed skewed X inactivation of approximately 75:25, whereas in the less severely affected twin (P1), X inactivation was close to 50:50. PDC activity was reduced in fibroblasts from both sibs, but to a greater extent in P2, and immunocytochemical staining of E1-alpha in patient fibroblasts showed reduced staining in both sibs, with a greater reduction in P2. Horga et al. (2019) concluded that these findings lent support to the hypothesis that the X inactivation pattern affects the phenotypic expression of PDHA1 mutations in heterozygous females. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Blass et al. (1971); Brown et al. (1989); Duran and Wadman (1985);
Haworth et al. (1976); Koike et al. (1988); Prick et al. (1981);
Robinson et al. (1980); Sheu et al. (1981); Willems et al. (1974)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Benke, P. J., Parker, J. C., Jr., Lubs, M.-L., Benkendorf, J., Feuer, A. E.
<strong>X-linked Leigh&#x27;s syndrome.</strong>
Hum. Genet. 62: 52-59, 1982.
[PubMed: 6891369]
[Full Text: https://doi.org/10.1007/BF00295603]
</p>
</li>
<li>
<p class="mim-text-font">
Bindoff, L. A., Birch-Machin, M. A., Farnsworth, L., Gardner-Medwin, D., Lindsay, J. G., Turnbull, D. M.
<strong>Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex.</strong>
J. Neurol. Sci. 93: 311-318, 1989.
[PubMed: 2592988]
[Full Text: https://doi.org/10.1016/0022-510x(89)90200-1]
</p>
</li>
<li>
<p class="mim-text-font">
Birch-Machin, M. A., Shepherd, I. M., Solomon, M., Yeaman, S. J., Gardner-Medwin, D., Sherratt, H. S. A., Lindsay, J. G., Aynsley-Green, A., Turnbull, D. M.
<strong>Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex.</strong>
J. Inherit. Metab. Dis. 11: 207-217, 1988.
[PubMed: 3139934]
[Full Text: https://doi.org/10.1007/BF01799876]
</p>
</li>
<li>
<p class="mim-text-font">
Blass, J. P., Avigan, J., Uhlendorf, B. W.
<strong>A defect in pyruvate decarboxylase in a child with an intermittent movement disorder.</strong>
J. Clin. Invest. 49: 423-432, 1970.
[PubMed: 4313434]
[Full Text: https://doi.org/10.1172/JCI106251]
</p>
</li>
<li>
<p class="mim-text-font">
Blass, J. P., Kark, R. A. P., Engel, W. K.
<strong>Clinical studies of a patient with pyruvate dehydrogenase deficiency.</strong>
Arch. Neurol. 25: 449-460, 1971.
[PubMed: 5110887]
[Full Text: https://doi.org/10.1001/archneur.1971.00490050083007]
</p>
</li>
<li>
<p class="mim-text-font">
Brown, G. K., Haan, E. A., Kirby, D. M., Scholem, R. D., Wraith, J. E., Rogers, J. G., Danks, D. M.
<strong>&#x27;Cerebral&#x27; lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis.</strong>
Europ. J. Pediat. 147: 10-14, 1988.
[PubMed: 3123240]
[Full Text: https://doi.org/10.1007/BF00442603]
</p>
</li>
<li>
<p class="mim-text-font">
Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M.
<strong>Pyruvate dehydrogenase deficiency.</strong>
J. Med. Genet. 31: 875-879, 1994.
[PubMed: 7853374]
[Full Text: https://doi.org/10.1136/jmg.31.11.875]
</p>
</li>
<li>
<p class="mim-text-font">
Brown, R. M., Dahl, H.-H. M., Brown, G. K.
<strong>X-chromosome localization of the functional gene for the E1-alpha subunit of the human pyruvate dehydrogenase complex.</strong>
Genomics 4: 174-181, 1989.
[PubMed: 2737678]
[Full Text: https://doi.org/10.1016/0888-7543(89)90297-8]
</p>
</li>
<li>
<p class="mim-text-font">
Brown, R. M., Otero, L. J., Brown, G. K.
<strong>Transfection screening for primary defects in the pyruvate dehydrogenase E1-alpha subunit gene.</strong>
Hum. Molec. Genet. 6: 1361-1367, 1997.
[PubMed: 9259285]
[Full Text: https://doi.org/10.1093/hmg/6.8.1361]
</p>
</li>
<li>
<p class="mim-text-font">
Brunette, M. G., Delvin, E., Hazel, B., Scriver, C. R.
<strong>Thiamine-responsive lactic acidosis in a patient with deficient low-Km pyruvate carboxylase activity in liver.</strong>
Pediatrics 50: 702-711, 1972.
[PubMed: 4343503]
</p>
</li>
<li>
<p class="mim-text-font">
Dahl, H.-H. M., Brown, G. K., Brown, R. M., Hansen, L. L., Kerr, D. S., Wexler, I. D., Patel, M. S., De Meirleir, L., Lissens, W., Chun, K., MacKay, N., Robinson, B. H.
<strong>Mutations and polymorphisms in the pyruvate dehydrogenase E1-alpha gene.</strong>
Hum. Mutat. 1: 97-102, 1992.
[PubMed: 1301207]
[Full Text: https://doi.org/10.1002/humu.1380010203]
</p>
</li>
<li>
<p class="mim-text-font">
Dahl, H.-H. M., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1-alpha subunit.</strong>
Hum. Mutat. 3: 152-155, 1994.
[PubMed: 8199595]
[Full Text: https://doi.org/10.1002/humu.1380030210]
</p>
</li>
<li>
<p class="mim-text-font">
Dahl, H.-H. M., Hansen, L. L., Brown, R. M., Danks, D. M., Rogers, J. G., Brown, G. K.
<strong>X-linked pyruvate dehydrogenase E1-alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.</strong>
J. Inherit. Metab. Dis. 15: 835-847, 1992.
[PubMed: 1293379]
[Full Text: https://doi.org/10.1007/BF01800219]
</p>
</li>
<li>
<p class="mim-text-font">
Dahl, H.-H. M., Maragos, C., Brown, R. M., Hansen, L. L., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency caused by deletion of a 7-bp repeat sequence in the E1-alpha gene.</strong>
Am. J. Hum. Genet. 47: 286-293, 1990.
[PubMed: 2378353]
</p>
</li>
<li>
<p class="mim-text-font">
de Meirleir, L., Specola, N., Seneca, S., Lissens, W.
<strong>Pyruvate dehydrogenase E1-alpha deficiency in a family: different clinical presentation in two siblings.</strong>
J. Inherit. Metab. Dis. 21: 224-226, 1998.
[PubMed: 9686362]
[Full Text: https://doi.org/10.1023/a:1005347501111]
</p>
</li>
<li>
<p class="mim-text-font">
Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.
[PubMed: 3930844]
[Full Text: https://doi.org/10.1007/BF01800663]
</p>
</li>
<li>
<p class="mim-text-font">
Endo, H., Hasegawa, K., Narisawa, K., Tada, K., Kagawa, Y., Ohta, S.
<strong>Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.</strong>
Am. J. Hum. Genet. 44: 358-364, 1989.
[PubMed: 2537010]
</p>
</li>
<li>
<p class="mim-text-font">
Evans, O. B.
<strong>Episodic weakness in pyruvate decarboxylase deficiency.</strong>
J. Pediat. 105: 961-963, 1984.
[PubMed: 6502351]
[Full Text: https://doi.org/10.1016/s0022-3476(84)80090-6]
</p>
</li>
<li>
<p class="mim-text-font">
Falk, R. E., Cederbaum, S. D., Blass, J. P., Gibson, G. E., Kark, R. A. P., Carrel, R. E.
<strong>Ketonic diet in the management of pyruvate dehydrogenase deficiency.</strong>
Pediatrics 58: 713-721, 1976.
[PubMed: 824610]
</p>
</li>
<li>
<p class="mim-text-font">
Farrell, D. F., Clark, A. F., Scott, C. R., Wennberg, R. P.
<strong>Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.</strong>
Science 187: 1082-1084, 1975.
[PubMed: 803713]
[Full Text: https://doi.org/10.1126/science.803713]
</p>
</li>
<li>
<p class="mim-text-font">
Fouque, F., Brivet, M., Boutron, A., Vequaud, C., Marsac, C., Zabot, M.-T., Benelli, C.
<strong>Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency.</strong>
Pediat. Res. 53: 793-799, 2003.
[PubMed: 12621116]
[Full Text: https://doi.org/10.1203/01.PDR.0000057987.46622.64]
</p>
</li>
<li>
<p class="mim-text-font">
Haworth, J. C., Perry, T. L., Blass, J. P., Hansen, S., Urguhart, N.
<strong>Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.</strong>
Pediatrics 58: 564-572, 1976.
[PubMed: 184426]
</p>
</li>
<li>
<p class="mim-text-font">
Horga, A., Woodward, C. E., Mills, A., Parees, I., Hargreaves, I. P., Brown, R. M., Bugiardini, E., Brooks, T., Manole, A., Remzova, E., Rahman, S., Reilly, M. M., Houlden, H., Sweeney, M. G., Brown, G. K., Polke, J. M., Gago, F., Parton, M. J., Piteathly, R. D. S., Hanna, M. G.
<strong>Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.</strong>
Hum. Genet. 138: 1313-1322, 2019.
[PubMed: 31673819]
[Full Text: https://doi.org/10.1007/s00439-019-02075-9]
</p>
</li>
<li>
<p class="mim-text-font">
Kerr, D. S., Berry, S. A., Lusk, M. M., Ho, L., Patel, M. S.
<strong>A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.</strong>
Pediat. Res. 24: 95-100, 1988.
[PubMed: 3137520]
[Full Text: https://doi.org/10.1203/00006450-198807000-00022]
</p>
</li>
<li>
<p class="mim-text-font">
Kissach, A. W., Currie, S., Harriman, D. G., Littlewood, J. M., Payne, R. B., Walker, B. E.
<strong>Leigh&#x27;s disease and failure of automatic respiration. (Letter)</strong>
Lancet 304: 662 only, 1974. Note: Originally Volume II.
[PubMed: 4137785]
[Full Text: https://doi.org/10.1016/s0140-6736(74)91995-3]
</p>
</li>
<li>
<p class="mim-text-font">
Koike, K., Ohta, S., Urata, Y., Kagawa, Y., Koike, M.
<strong>Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase.</strong>
Proc. Nat. Acad. Sci. 85: 41-45, 1988.
[PubMed: 3422424]
[Full Text: https://doi.org/10.1073/pnas.85.1.41]
</p>
</li>
<li>
<p class="mim-text-font">
Lissens, W., Vreken, P., Barth, P. G., Wijburg, F. A., Ruitenbeek, W., Wanders, R. J. A., Seneca, S., Liebaers, I., De Meirleir, L.
<strong>Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1-alpha gene.</strong>
Europ. J. Pediat. 158: 853-857, 1999.
[PubMed: 10486093]
[Full Text: https://doi.org/10.1007/s004310051222]
</p>
</li>
<li>
<p class="mim-text-font">
Livingstone, I. R., Gardner-Medwin, D., Pennington, R. J. T.
<strong>Familial intermittent ataxia with possible X-linked recessive inheritance: two patients with abnormal pyruvate metabolism and a response to acetazolamide.</strong>
J. Neurol. Sci. 64: 89-97, 1984.
[PubMed: 6539810]
[Full Text: https://doi.org/10.1016/0022-510x(84)90059-5]
</p>
</li>
<li>
<p class="mim-text-font">
Lonsdale, D., Faulkner, W. R., Price, J. M., Smeby, R. R.
<strong>Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperphenylalaninemia and hyperalaninuria.</strong>
Pediatrics 43: 1025-1034, 1969.
[PubMed: 5786203]
</p>
</li>
<li>
<p class="mim-text-font">
Matthews, P. M., Brown, R. M., Otero, L. J., Marchington, D. R., LeGris, M., Howes, R., Meadows, L. S., Shevell, M., Scriver, C. R., Brown, G. K.
<strong>Pyruvate dehydrogenase deficiency: clinical presentation and molecular genetic characterization of five new patients.</strong>
Brain 117: 435-443, 1994.
[PubMed: 8032855]
[Full Text: https://doi.org/10.1093/brain/117.3.435]
</p>
</li>
<li>
<p class="mim-text-font">
Matthews, P. M., Marchington, D. R., Squier, M., Land, J., Brown, R. M., Brown, G. K.
<strong>Molecular genetic characterization of an X-linked form of Leigh&#x27;s syndrome.</strong>
Ann. Neurol. 33: 652-655, 1993.
[PubMed: 8498846]
[Full Text: https://doi.org/10.1002/ana.410330616]
</p>
</li>
<li>
<p class="mim-text-font">
McCormick, K., Viscardi, R. M., Robinson, B., Heininger, J.
<strong>Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate.</strong>
Am. J. Med. Genet. 22: 291-299, 1985.
[PubMed: 4050860]
[Full Text: https://doi.org/10.1002/ajmg.1320220211]
</p>
</li>
<li>
<p class="mim-text-font">
Montpetit, V. J., Andermann, F., Carpenter, S.
<strong>Subacute necrotizing encephalomyelopathy: a review and a study of two families.</strong>
Brain 94: 1-30, 1971.
[PubMed: 5552162]
[Full Text: https://doi.org/10.1093/brain/94.1.1]
</p>
</li>
<li>
<p class="mim-text-font">
Naito, E., Ito, M., Takeda, E., Yokota, I., Yoshijima, S., Kuroda, Y.
<strong>Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.</strong>
Pediat. Res. 36: 340-346, 1994.
[PubMed: 7808831]
[Full Text: https://doi.org/10.1203/00006450-199409000-00013]
</p>
</li>
<li>
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Kuroda, Y.
<strong>Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex.</strong>
Europ. J. Pediat. 157: 648-652, 1998.
[PubMed: 9727848]
[Full Text: https://doi.org/10.1007/s004310050903]
</p>
</li>
<li>
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Ogawa, Y., Kitamura, S., Takada, E., Horii, Y., Kuroda, Y.
<strong>Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region.</strong>
Biochim. Biophys. Acta 1588: 79-84, 2002.
[PubMed: 12379317]
[Full Text: https://doi.org/10.1016/s0925-4439(02)00142-4]
</p>
</li>
<li>
<p class="mim-text-font">
Naito, E., Ito, M., Yokota, I., Saijo, T., Matsuda, J., Osaka, H., Kimura, S., Kuroda, Y.
<strong>Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.</strong>
J. Inherit. Metab. Dis. 20: 539-548, 1997.
[PubMed: 9266390]
[Full Text: https://doi.org/10.1023/a:1005305614374]
</p>
</li>
<li>
<p class="mim-text-font">
Okajima, K., Warman, M. L., Byrne, L. C., Kerr, D. S.
<strong>Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype.</strong>
Molec. Genet. Metab. 87: 162-168, 2006.
[PubMed: 16412675]
[Full Text: https://doi.org/10.1016/j.ymgme.2005.09.023]
</p>
</li>
<li>
<p class="mim-text-font">
Pirot, N., Crahes, M., Adle-Biassette, H., Soares, A., Bucourt, M., Boutron, A., Carbillon, L., Mignot, C., Trestard, L., Bekri, S., Laquerriere, A.
<strong>Phenotypic and neuropathological characterization of fetal pyruvate dehydrogenase deficiency.</strong>
J. Neuropath. Exp. Neurol. 75: 227-238, 2016.
[PubMed: 26865159]
[Full Text: https://doi.org/10.1093/jnen/nlv022]
</p>
</li>
<li>
<p class="mim-text-font">
Prick, M., Gabreels, F., Renier, W., Trijbels, F., Jaspar, H., Lamers, K., Kok, J.
<strong>Pyruvate dehydrogenase deficiency restricted to brain.</strong>
Neurology 31: 398-404, 1981.
[PubMed: 6783978]
[Full Text: https://doi.org/10.1212/wnl.31.4.398]
</p>
</li>
<li>
<p class="mim-text-font">
Robinson, B. H., MacMillan, H., Petrova-Benedict, R., Sherwood, W. G.
<strong>Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex.</strong>
J. Pediat. 111: 525-533, 1987.
[PubMed: 3116190]
[Full Text: https://doi.org/10.1016/s0022-3476(87)80112-9]
</p>
</li>
<li>
<p class="mim-text-font">
Robinson, B. H., Sherwood, W. G.
<strong>Lactic acidaemia.</strong>
J. Inherit. Metab. Dis. 7: 69-73, 1984.
[PubMed: 6434848]
[Full Text: https://doi.org/10.1007/BF03047378]
</p>
</li>
<li>
<p class="mim-text-font">
Robinson, B. H., Taylor, J., Sherwood, W. G.
<strong>The genetic heterogeneity of lactic acidosis: occurrence of recognisable inborn errors of metabolism in a pediatric population with lactic acidosis.</strong>
Pediat. Res. 14: 956-962, 1980.
[PubMed: 6775276]
[Full Text: https://doi.org/10.1203/00006450-198008000-00013]
</p>
</li>
<li>
<p class="mim-text-font">
Sheu, K. R., Hu, C.-W. C., Utter, M. F.
<strong>Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts.</strong>
J. Clin. Invest. 67: 1463-1471, 1981.
[PubMed: 6262377]
[Full Text: https://doi.org/10.1172/jci110176]
</p>
</li>
<li>
<p class="mim-text-font">
Shevell, M. I., Matthews, P. M., Scriver, C. R., Brown, R. M., Otero, L. J., Legris, M., Brown, G. K., Arnold, D. L.
<strong>Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency.</strong>
Pediat. Neurol. 11: 224-229, 1994.
[PubMed: 7880337]
[Full Text: https://doi.org/10.1016/0887-8994(94)90107-4]
</p>
</li>
<li>
<p class="mim-text-font">
Stromme, J. H., Borud, O., Moe, P. J.
<strong>Fatal lactic acidosis in a newborn attributable to a congenital defect of pyruvate dehydrogenase.</strong>
Pediat. Res. 10: 62-66, 1976.
[PubMed: 813176]
[Full Text: https://doi.org/10.1203/00006450-197601000-00012]
</p>
</li>
<li>
<p class="mim-text-font">
Takakubo, F., Cartwright, P., Hoogenraad, N., Thorburn, D. R., Collins, F., Lithgow, T., Dahl, H.-H. M.
<strong>An amino acid substitution in the pyruvate dehydrogenase E1-alpha gene, affecting mitochondrial import of the precursor protein.</strong>
Am. J. Hum. Genet. 57: 772-780, 1995.
[PubMed: 7573035]
</p>
</li>
<li>
<p class="mim-text-font">
Wexler, I. D., Hemalatha, S. G., Liu, T.-C., Berry, S. A., Kerr, D. S., Patel, M. S.
<strong>A mutation in the E1-alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency.</strong>
Pediat. Res. 32: 169-174, 1992.
[PubMed: 1508605]
[Full Text: https://doi.org/10.1203/00006450-199208000-00009]
</p>
</li>
<li>
<p class="mim-text-font">
Wexler, I. D., Kerr, D. S., Ho, L., Lusk, M. M., Pepin, R. A., Javed, A. A., Mole, J. E., Jesse, B. W., Thekkumkara, T. J., Pons, G., Patel, M. S.
<strong>Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.</strong>
Proc. Nat. Acad. Sci. 85: 7336-7340, 1988.
[PubMed: 3140238]
[Full Text: https://doi.org/10.1073/pnas.85.19.7336]
</p>
</li>
<li>
<p class="mim-text-font">
Wick, H., Schweizer, K., Baumgartner, R.
<strong>Thiamine dependency in a patient with congenital lacticacidaemia due to pyruvate dehydrogenase deficiency.</strong>
Agents Actions 7: 405-410, 1977.
[PubMed: 413346]
[Full Text: https://doi.org/10.1007/BF01969575]
</p>
</li>
<li>
<p class="mim-text-font">
Wicking, C. A., Brown, G. K., Scholem, R. D., Hunt, S. M., Dahl, H.-H. M.
<strong>Molecular analysis of pyruvate dehydrogenase deficiency. (Abstract)</strong>
Am. J. Hum. Genet. 37: A182 only, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Willems, J. L., Monnens, L. A. H., Trijbels, J. M. F., Sengers, R. C. A., Veerkamp, J. H.
<strong>Pyruvate decarboxylase deficiency in liver. (Letter)</strong>
New Eng. J. Med. 290: 406-407, 1974.
[PubMed: 4810126]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 01/12/2021<br>Hilary J. Vernon - updated : 09/21/2020<br>Cassandra L. Kniffin - updated : 10/28/2014<br>Cassandra L. Kniffin - updated : 1/4/2010<br>Victor A. McKusick - updated : 7/14/2004<br>Cassandra L. Kniffin - reorganized : 7/14/2004<br>Cassandra L. Kniffin - updated : 7/9/2004
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin : 7/6/2004
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 08/08/2023<br>carol : 01/13/2021<br>carol : 01/12/2021<br>carol : 09/21/2020<br>carol : 08/03/2020<br>alopez : 05/15/2019<br>carol : 02/09/2018<br>carol : 08/17/2017<br>carol : 11/03/2014<br>mcolton : 10/29/2014<br>ckniffin : 10/28/2014<br>carol : 2/3/2012<br>ckniffin : 2/1/2012<br>ckniffin : 1/31/2012<br>carol : 7/22/2011<br>terry : 4/21/2011<br>wwang : 2/16/2010<br>ckniffin : 1/4/2010<br>wwang : 12/6/2005<br>ckniffin : 12/2/2005<br>alopez : 6/13/2005<br>terry : 3/3/2005<br>terry : 2/10/2005<br>tkritzer : 7/23/2004<br>tkritzer : 7/19/2004<br>ckniffin : 7/15/2004<br>terry : 7/14/2004<br>carol : 7/14/2004<br>ckniffin : 7/9/2004
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
</div>
</div>
</div>
<div class="visible-print-block mim-footer" style="position: relative;">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
<br />
Printed: March 13, 2025
</div>
</div>
</div>
</div>
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
<div class="modal-dialog" role="document">
<div class="modal-content">
<div class="modal-header">
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">&times;</span></button>
<h4 class="modal-title" id="mimDonationPopupModalTitle">
OMIM Donation:
</h4>
</div>
<div class="modal-body">
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Dear OMIM User,
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
To ensure long-term funding for the OMIM project, we have diversified
our revenue stream. We are determined to keep this website freely
accessible. Unfortunately, it is not free to produce. Expert curators
review the literature and organize it to facilitate your work. Over 90%
of the OMIM's operating expenses go to salary support for MD and PhD
science writers and biocurators. Please join your colleagues by making a
donation now and again in the future. Donations are an important
component of our efforts to ensure long-term funding to provide you the
information that you need at your fingertips.
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Thank you in advance for your generous support, <br />
Ada Hamosh, MD, MPH <br />
Scientific Director, OMIM <br />
</p>
</div>
</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
Reference in a new issue View git blame Copy permalink