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<meta name="description" content="Benign COX deficiency is better described as &#x27;reversible infantile respiratory chain deficiency&#x27;. It is genetically heterogeneous, and patients not carrying the m.14674T&gt;C or T&gt;G mt-tRNA(Glu) mutations may have mutations in the TRMU gene. Diagnosing this disorder at the molecular level is a si …"><meta name="keywords" content="pmid:21931168, PMC4562368, doi:10.1136/jmg.2011.089995, Research Support, Non-U.S. Gov&#x27;t, J Uusimaa, H Jungbluth, J Poulton, Acidosis, Lactic / genetics, Acidosis, Lactic / metabolism, Adolescent, Adult, Amino Acid Sequence, Animals, Brain / pathology, Child, Child, Preschool, Cytochrome-c Oxidase Deficiency / genetics*, Cytochrome-c Oxidase Deficiency / metabolism, Cytochrome-c Oxidase Deficiency / pathology, Electron Transport Complex IV / genetics, Face / pathology, Family, Female, Genetic Heterogeneity, Histocytochemistry, Humans, Infant, Infant, Newborn, Liver / pathology, Magnetic Resonance Imaging, Male, Mitochondrial Proteins / genetics, Molecular Sequence Data, Muscle Hypotonia, Muscle, Skeletal / pathology, Mutation / genetics, Sequence Alignment, tRNA Methyltransferases / genetics, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/21931168/"><meta property="og:description" content="Benign COX deficiency is better described as &#x27;reversible infantile respiratory chain deficiency&#x27;. It is genetically heterogeneous, and patients not carrying the m.14674T&gt;C or T&gt;G mt-tRNA(Glu) mutations may have mutations in the TRMU gene. Diagnosing this disorder at the molecular level is a si …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/21931168/"><meta name="twitter:description" content="Benign COX deficiency is better described as &#x27;reversible infantile respiratory chain deficiency&#x27;. It is genetically heterogeneous, and patients not carrying the m.14674T&gt;C or T&gt;G mt-tRNA(Glu) mutations may have mutations in the TRMU gene. Diagnosing this disorder at the molecular level is a si …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21931168">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://jmg.bmj.com/lookup/pmidlookup?view=long&amp;pmid=21931168"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3051&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21931168&amp;db=pubmed&amp;nlmid=2985087R"
title="See full text options at HighWire"
data-ga-category="full_text"
data-ga-action="HighWire"
data-ga-label="21931168"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-bmjjournals_final.gif" alt="HighWire full text link"><span class="text">
HighWire
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21931168/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21931168&amp;db=pubmed&amp;nlmid=2985087R"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21931168"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21931168/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21931168/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21931168" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21931168%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="qnaCO1bv9dHJpRoxxTtnPQQZ4VmngEuRHaUHrRERJOudjiunac6pjYmDCZ4z9f2b"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
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<h1 class="heading-title">
Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease
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Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease
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><sup class="key">1</sup> Nuffield Department of Obstetrics and Gynaecology, University of Oxford, The Women&#x27;s Centre, John Radcliffe Hospital, Oxford, UK.</li>
<li data-affiliation-id="short-view-affiliation-2"
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><sup class="key">2</sup> Department of Clinical Neuroscience, King&#x27;s College Hospital, London, UK.</li>
<li data-affiliation-id="short-view-affiliation-3"
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><sup class="key">3</sup> Department of Paediatric Neurology - Neuromuscular Service, Evelina Children&#x27;s Hospital, St Thomas&#x27; Hospital, London, UK.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Oxford Medical Genetics Lab, Churchill Hospital, Oxford, UK.</li>
<li data-affiliation-id="short-view-affiliation-5"
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><sup class="key">5</sup> Servizio di Puericultura, Universita&#x27; di Cagliari, Italy.</li>
<li data-affiliation-id="short-view-affiliation-6"
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><sup class="key">6</sup> Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.</li>
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><sup class="key">7</sup> Unit of Molecular Neurogenetics, &quot;C. Besta&quot; Neurological Institute - IRCCS Foundation, Milan, Italy.</li>
<li data-affiliation-id="short-view-affiliation-8"
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><sup class="key">8</sup> Department of Paediatric Neurology, Manchester Children&#x27;s Hospital, Manchester, UK.</li>
<li data-affiliation-id="short-view-affiliation-9"
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><sup class="key">9</sup> National Centre for Inherited Metabolic Disease, Children&#x27;s University Hospital, Dublin Republic of Ireland.</li>
<li data-affiliation-id="short-view-affiliation-10"
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><sup class="key">10</sup> Centre for Statistics in Medicine, University of Oxford, UK.</li>
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><sup class="key">11</sup> Department of Biochemistry, University of Oxford, UK.</li>
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><sup class="key">12</sup> Our Lady&#x27;s Hospital for Sick Children, Dublin, Ireland.</li>
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Objectives:
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Homoplasmic maternally inherited, m.14674T&gt;C or m. 14674T&gt;G mt-tRNA(Glu) mutations have recently been identified in reversible infantile cytochrome c oxidase deficiency (or 'benign COX deficiency'). This study sought other genetic defects that may give rise to similar presentations.
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Eight patients from seven families with clinicopathological features of infantile reversible cytochrome c oxidase deficiency were investigated.
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The study reviewed the diagnostic features and performed molecular genetic analyses of mitochondrial DNA and nuclear encoded candidate genes.
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Patients presented with subacute onset of profound hypotonia, feeding difficulties and lactic acidosis within the first months of life. Although recovery was remarkable, a mild myopathy persisted into adulthood. Histopathological findings in muscle included increased lipid and/or glycogen content, ragged-red and COX negative fibres. Biochemical studies suggested more generalised abnormalities than pure COX deficiency. Clinical improvement was reflected by normalisation of lactic acidosis and histopathological abnormalities. The m.14674T&gt;C mt-tRNA(Glu) mutation was identified in four families, but none had the m. 14674T&gt;G mutation. Furthermore, in two families pathogenic mutations were also found in the nuclear TRMU gene which has not previously been associated with this phenotype. In one family, the genetic aetiology still remains unknown.
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Benign COX deficiency is better described as 'reversible infantile respiratory chain deficiency'. It is genetically heterogeneous, and patients not carrying the m.14674T&gt;C or T&gt;G mt-tRNA(Glu) mutations may have mutations in the TRMU gene. Diagnosing this disorder at the molecular level is a significant advance for paediatric neurologists and intensive care paediatricians, enabling them to select children with an excellent prognosis for continuing respiratory support from those with severe mitochondrial presentation in infancy.
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<div class="figure-caption-contents"><p> Typical facial features associated with… </p></div>
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<div class="figure-caption-contents"><p> Typical facial features associated with Reversible Infantile Respiratory Chain Deficiency due to the… </p></div>
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Figure 1
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<div class="figure-caption-contents">Typical facial features associated with Reversible Infantile Respiratory Chain Deficiency due to the m.14674T>C mt-tRNA<sup>Glu</sup> mutation, Patient 3 (B, C) and Patient 4 (A). There is a myopathic facial appearance (A-C) with an elongated face and chin, bilateral ptosis, narrowed upslanting palpebral fissures and an elongated, prominent nose. Inability to bury the eyelashes completely (C) is reflective of mild facial weakness.</div>
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<div class="figure-caption-contents"><p> Brain MRI at day 26… </p></div>
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<div class="figure-caption-contents"><p> Brain MRI at day 26 of life of Patient 8 with a compound… </p></div>
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Figure 2
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<div class="figure-caption-contents">Brain MRI at day 26 of life of Patient 8 with a compound heterozygous mutation p. V279M, (c.G835A)/IVS11-3, C>G in <i>TRMU</i> gene. An abnormal high signal focus in right thalamus in T1 image (A). Brain MR spectroscopy centred on the left basal ganglia and thalamus with TE 35 showing an abnormal double peak at 1.3ppm (arrow) (B). When MRS was repeated with TE 144 this double peak at 1.3ppm inverted which is characteristic of lactate (C).</div>
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<p> Figure 2 </p>
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<div class="figure-caption-contents"><p> Brain MRI at day 26… </p></div>
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<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Brain MRI at day 26 of life of Patient 8 with a compound… </p></div>
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Figure 2
</strong>
<div class="figure-caption-contents">Brain MRI at day 26 of life of Patient 8 with a compound heterozygous mutation p. V279M, (c.G835A)/IVS11-3, C>G in <i>TRMU</i> gene. An abnormal high signal focus in right thalamus in T1 image (A). Brain MR spectroscopy centred on the left basal ganglia and thalamus with TE 35 showing an abnormal double peak at 1.3ppm (arrow) (B). When MRS was repeated with TE 144 this double peak at 1.3ppm inverted which is characteristic of lactate (C).</div>
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<p> Figure 2 </p>
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<div class="figure-caption-contents"><p> Brain MRI at day 26… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Brain MRI at day 26 of life of Patient 8 with a compound… </p></div>
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Figure 2
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<div class="figure-caption-contents">Brain MRI at day 26 of life of Patient 8 with a compound heterozygous mutation p. V279M, (c.G835A)/IVS11-3, C>G in <i>TRMU</i> gene. An abnormal high signal focus in right thalamus in T1 image (A). Brain MR spectroscopy centred on the left basal ganglia and thalamus with TE 35 showing an abnormal double peak at 1.3ppm (arrow) (B). When MRS was repeated with TE 144 this double peak at 1.3ppm inverted which is characteristic of lactate (C).</div>
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<p> Figure 3 </p>
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<div class="figure-caption-contents"><p> Histopathological features associated with Reversible… </p></div>
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<p> Figure 3 </p>
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<div class="figure-caption-contents"><p> Histopathological features associated with Reversible Infantile Respiratory Chain Deficiency due to the m.14674T… </p></div>
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Figure 3
</strong>
<div class="figure-caption-contents">Histopathological features associated with Reversible Infantile Respiratory Chain Deficiency due to the m.14674T>C mt-tRNA<sup>Glu</sup> mutation. Transverse sections of muscle biopsies from the quadriceps of Patient 5, at 4 months of age (A-B; D-E), and from Patient 1 on follow-up biopsy at 28 years of age (C, F). Serial sections from Patient 5 stained for combined SDH-COX activity (A) show numerous COX negative fibres (blue appearance), several with reduced COX (blue/greyappearance) and only a few COX positive fibres (brown appearance); COX negative fibres have a ragged-red appearance on the Gomori trichrome stain (D) and some correspond to type 1 fibres, dark with slow myosin (B) and light on fast myosin stains (E). There is co-expression of both myosin isoforms in some fibres and several of the very atrophic fibres are type 1/slow fibres. On the repeat muscle biopsy from Patient 1 obtained at 28 years there is increased variability in fibre size, a mild increase in connective tissue on H&amp;E (C), and marked type 2 predominance on ATPase pre-incubated at a pH of 4.6 with atrophy of type 1 fibres (F).</div>
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<p> Figure 4 </p>
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<div class="figure-caption-contents"><p> Histological findings in liver in… </p></div>
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<p> Figure 4 </p>
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<div class="figure-caption-contents"><p> Histological findings in liver in Patient 8 with reversible infantile respiratory chain deficiency… </p></div>
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Figure 4
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<div class="figure-caption-contents">Histological findings in liver in Patient 8 with reversible infantile respiratory chain deficiency with acute infantile liver failure associated with a compound heterozygous mutation p. V279M, (c.G835A)/IVS11-3, C>G in TRMU gene. Liver parenchyma showng central hepatic rosette with cholestasis. Hepatocytes exhibit prominent haemosiderin and microvesicular steatosis. (Hematoxylin and Eosin)</div>
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<div class="figure-caption-contents"><p> Mutations is <i> TRMU </i> gene in… </p></div>
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<div class="figure-caption-contents"><p> Mutations is <i> TRMU </i> gene in two patients with reversible infantile respiratory chain deficiency.… </p></div>
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Figure 5
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<div class="figure-caption-contents">Mutations is <i>TRMU</i> gene in two patients with reversible infantile respiratory chain deficiency. 3A) a heterozygous p.A10S (c.G28T) in Patient 7 and 3B, and 3C) A compound heterozygous mutation p. V279M, (c.G835A)/IVS11-3, C&gt;G Patient 8. 3D) Multiple sequence alignment of the TRMU protein with eukaryotic homologues showing the conservation of alanine in site 10 and valine in site 279.</div>
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DiMauro S, Nicholson JF, Hays AP, et al. Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency. Trans Am Neurol Assoc. 1981;106:2057.
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