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Entry
- #261515 - D-BIFUNCTIONAL PROTEIN DEFICIENCY
- OMIM
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<span class="h4">#261515</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/261515"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<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>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=(D-BIFUNCTIONAL PROTEIN DEFICIENCY) OR (HSD17B4)" 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="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3578&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/2093" 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/condition/d-bifunctional-protein-deficiency" 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=261515[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="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/fc431af7-4658-444f-9923-5aea26770f62/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>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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<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:0090031" 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/261515" 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:0090031" 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>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
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</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:261515" 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>
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</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>
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</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> 238068007<br />
<strong>ORPHA:</strong> 300<br />
<strong>DO:</strong> 0090031<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>
261515
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
D-BIFUNCTIONAL PROTEIN DEFICIENCY
</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">
17-BETA-HYDROXYSTEROID DEHYDROGENASE IV DEFICIENCY<br />
DBP DEFICIENCY<br />
PEROXISOMAL BIFUNCTIONAL ENZYME DEFICIENCY<br />
PBFE DEFICIENCY
</span>
</h4>
</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/5/392?start=-3&limit=10&highlight=392">
5q23.1
</a>
</span>
</td>
<td>
<span class="mim-font">
D-bifunctional protein deficiency
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/261515"> 261515 </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">
HSD17B4
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601860"> 601860 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
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<div class="btn-group ">
<a href="/clinicalSynopsis/261515" 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')">
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&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>
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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/261515" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/261515" 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">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</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> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive (44% of patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</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">
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&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 /> -
Scaphocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109418001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109418001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265534</a>, <a href="https://bioportal.bioontology.org/search?q=C0432123&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0432123</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030799</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030799</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Dolichocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e&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 /> -
Large fontanelles <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276709006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276709006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000239" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000239</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000239" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000239</a>]</span><br /> -
Delayed closure of the fontanelles <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82779003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82779003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0277828&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0277828</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000270</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">
- Facial dysmorphism (68%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248200007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248200007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398302004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398302004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32003007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32003007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398206004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398206004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424503&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424503</a>, <a href="https://bioportal.bioontology.org/search?q=C0266617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000271" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000271</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001999</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001999</a>]</span><br /> -
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 /> -
High forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239676</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000348</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000348</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Hairline,High_Anterior-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec&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 /> -
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882&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 /> -
Retrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109515000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109515000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035353</a>, <a href="https://bioportal.bioontology.org/search?q=C3494422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3494422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Retrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba&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> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low-set ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95515009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95515009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q17.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q17.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239234&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239234</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ear,Low-Set-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931&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 /> -
Loss of hearing (45%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><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">
- Upslanting palpebral fissures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246799009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246799009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423109</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000582" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000582</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000582" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000582</a>]</span><br /> -
Epicanthal folds <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74824007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74824007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678230</a>, <a href="https://bioportal.bioontology.org/search?q=C0229249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0229249</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span><br /> -
Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a&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 /> -
Visual impairment (55%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246635007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246635007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397540003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042798</a>, <a href="https://bioportal.bioontology.org/search?q=C3665347&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665347</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span><br /> -
Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
Failure to fixate on objects <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849989&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849989</a>]</span><br /> -
Loss of vision (34%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246635007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246635007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H54.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H54.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/369.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">369.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3665346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665346</a>, <a href="https://bioportal.bioontology.org/search?q=C3665386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665386</a>, <a href="https://bioportal.bioontology.org/search?q=C0042798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042798</a>, <a href="https://bioportal.bioontology.org/search?q=C0456909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>]</span><br /> -
Abolished electroretinogram (ERG) (76%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855685</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000550</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000550</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">
- Depressed nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17&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> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- High-arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Funnel chest <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/391987005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">391987005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/391982004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">391982004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016842&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016842</a>, <a href="https://bioportal.bioontology.org/search?q=C2051831&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2051831</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000767" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000767</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000767" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000767</a>]</span><br /> -
Long, small thorax <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849974&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849974</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Abnormal liver function (26%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75183008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75183008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001410" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001410</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
Hepatomegaly (43%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
Histology shows normal numbers of peroxisomes (84%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849978&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849978</a>]</span><br /> -
Abnormal peroxisomes (53%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849979&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849979</a>]</span><br /> -
Absence of peroxisomes (16%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4314641&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4314641</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034553</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034553</a>]</span><br /> -
Cholestasis (9%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30144000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30144000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33688009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33688009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197446008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197446008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K83.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K83.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/576.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">576.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008370</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span><br /> -
Steatosis (22%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/442191002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">442191002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187537008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187537008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197321007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29185008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29185008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2711227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2711227</a>, <a href="https://bioportal.bioontology.org/search?q=C0152254&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152254</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</a>]</span><br /> -
Fibrosis (22%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263756000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263756000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/112674009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">112674009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016059&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016059</a>]</span><br /> -
Hemosiderosis (13%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39011001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39011001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399187006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399187006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399144008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399144008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E83.110" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E83.110</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/E83.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E83.11</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/E83.119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E83.119</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019114</a>, <a href="https://bioportal.bioontology.org/search?q=C0018995&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018995</a>]</span><br /> -
Proliferation of bile canaliculi (9%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20239009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20239009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0267818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0267818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001408" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001408</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001408" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001408</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor feeding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</a>, <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Renal cysts (33%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/722223000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">722223000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887499&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887499</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000107" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000107</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000107" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000107</a>]</span><br /> -
Adrenal cortex atrophy (42%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1217048002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1217048002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151510</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Generalized osteopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312894000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312894000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029453</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000938</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000938</a>]</span><br /> -
Delayed bone maturation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123983008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123983008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541764</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span><br /> -
Calcific stippling <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849993&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849993</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002832" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002832</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002832" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002832</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Claw hands <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299034005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5550991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5550991</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Talipes equinovarus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br /> -
Hammertoes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/122481008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">122481008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1136179&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1136179</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001765" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001765</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001765" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001765</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Decreased muscle mass <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837108&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837108</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003199</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003199</a>]</span><br />
</span>
</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, neonatal (> 90%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205294008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2267233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2267233</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span><br /> -
Seizures (> 90%) <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 /> -
Delayed psychomotor development, severe (> 90%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847696&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847696</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Polymicrogyria (64%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4945003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4945003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266464</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span><br /> -
Ventricular dilatation (29%) <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 /> -
White matter dysmyelination/demyelination (71%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4020810&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4020810</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007266</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007266</a>]</span><br /> -
Neocortical dysplasia (27%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253153000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253153000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002539" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002539</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002539" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002539</a>]</span><br /> -
Hypoplastic/atrophic corpus callosum (55%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849966&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849966</a>]</span><br /> -
Heterotopic neurons in the white matter (36%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849967&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849967</a>]</span><br /> -
Generalized cerebral hypoplasia/atrophy (45%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4024945&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4024945</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007058</a>]</span><br /> -
Cerebellar hypoplasia/atrophy (27%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279222&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279222</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007360</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007360</a>]</span><br /> -
Gliosis (27%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/359580009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">359580009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81415000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81415000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887640&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887640</a>, <a href="https://bioportal.bioontology.org/search?q=C0017639&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017639</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002171</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002446" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002446</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002171</a>]</span><br />
</span>
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<div>
<span class="h5 mim-font">
<em> Peripheral Nervous System </em>
</span>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed peripheral nerve motor conduction velocities (67%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849971&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849971</a>]</span><br />
</span>
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<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
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<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Adrenocortical insufficiency (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386584007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386584007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/255.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">255.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0405580&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0405580</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008207" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008207</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008207" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008207</a>]</span><br />
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<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
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<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Amniotic Fluid </em>
</span>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Polyhydramnios <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86203003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86203003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/657.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">657.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/657" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">657</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001561" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001561</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001561" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001561</a>]</span><br /> -
Fetal ascites <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363125002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363125002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1285291&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1285291</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001791" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001791</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001791" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001791</a>]</span><br />
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<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
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- Increased plasma levels of very long-chain fatty acids (VLCFA) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849994</a>]</span><br /> -
Increased plasma levels of bile acid intermediates <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849995&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849995</a>]</span><br /> -
Decreased peroxisomal fatty acid beta-oxidation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849996&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849996</a>]</span><br /> -
Decreased or absent D-bifunctional protein activity and protein <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849997&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849997</a>]</span><br /> -
Normal serum plasmalogen <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849691&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849691</a>]</span><br />
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<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
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- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
Early death, usually before age 2 years<br /> -
Prevalence of 1 in 100,000<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutations in the 17-beta-hydroxysteroid dehydrogenase IV gene (HSD17B4, <a href="/entry/601860#0001">601860.0001</a>)<br />
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<p>A number sign (#) is used with this entry because D-bifunctional protein deficiency can be caused by homozygous or compound heterozygous mutation in the HSD17B4 gene (<a href="/entry/601860">601860</a>) on chromosome 5q2, which encodes the D-bifunctional protein (DBP).</p>
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<p>D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (<a href="/entry/264470">264470</a>), caused by mutation in the ACOX1 gene (<a href="/entry/609751">609751</a>) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; <a href="/entry/300100">300100</a>), Zellweger cerebrohepatorenal syndrome (see <a href="/entry/214100">214100</a>) and neonatal adrenoleukodystrophy (NALD; see <a href="/entry/601539">601539</a>) (<a href="#23" class="mim-tip-reference" title="Watkins, P. A., McGuinness, M. C., Raymond, G. V., Hicks, B. A., Sisk, J. M., Moser, A. B., Moser, H. W. &lt;strong&gt;Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies.&lt;/strong&gt; Ann. Neurol. 38: 472-477, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7668838/&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;7668838&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410380322&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="7668838">Watkins et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668838" 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>DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. <a href="#8" class="mim-tip-reference" title="McMillan, H. J., Worthylake, T., Schwartzentruber, J., Gottlieb, C. C., Lawrence, S. E., MacKenzie, A., Beaulieu, C. L., Mooyer, P. A. W., FORGE Canada Consortium, Wanders, R. J. A., Majewski, J., Bulman, D. E., Geraghty, M. T., Ferdinandusse, S., Boycott, K. M. &lt;strong&gt;Specific combination of compound heterozygous mutations in 17-beta-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency.&lt;/strong&gt; Orphanet J. Rare Dis. 7: 90, 2012. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23181892/&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;23181892&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23181892[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/10.1186/1750-1172-7-90&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="23181892">McMillan et al. (2012)</a> proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; <a href="/entry/233400">233400</a>). <a href="#12" class="mim-tip-reference" title="Pierce, S. B., Walsh, T., Chisholm, K. M., Lee, M, K., Thornton, A. M., Fiumara, A., Opitz, J. M., Levy-Lahad, E., Klevit, R. E., King, M.-C. &lt;strong&gt;Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 87: 282-288, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20673864/&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;20673864&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20673864[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/10.1016/j.ajhg.2010.07.007&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="20673864">Pierce et al. (2010)</a> noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23181892+20673864" 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>
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<p><a href="#22" class="mim-tip-reference" title="Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., Jr., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E., Moser, H. W. &lt;strong&gt;Peroxisomal bifunctional enzyme deficiency.&lt;/strong&gt; J. Clin. Invest. 83: 771-777, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2921319/&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;2921319&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113956&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="2921319">Watkins et al. (1989)</a> reported a black male infant with neonatal hypotonia and macrocephaly who developed seizures and required ventilatory support for the first 4 days of life. By 6 weeks of age, he had made no developmental progress, seizures continued, and the fontanels were large. Brain biopsy at 6 weeks of age showed polymicrogyria. He also had generalized osteopenia with delayed bone maturation. He died at 5.5 months as a result of an acute necrotizing enterocolitis. Postmortem examination showed small adrenal glands with a normal medulla and replacement of the entire cortex with a single type of lipid-containing 'balloon' cell. The changes were identical to those of seen in X-linked and autosomal recessive neonatal forms of adrenoleukodystrophy. Very long-chain fatty acids were increased in the patient's plasma and fibroblasts, and beta-oxidation was impaired. However, biochemical analysis distinguished the disorder from the other forms of ALD: cultured fibroblasts had normal levels of serum phytanic acid and L-pipecolic acid and normal plasmalogen synthesis. In addition, electron microscopy and catalase subcellular distribution studies showed that peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes showed deficiency of the L-bifunctional enzyme (LBP; enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase; <a href="/entry/607037">607037</a>), whereas acyl-CoA oxidase and the mature form of peroxisomal 3-oxoacyl-CoA thiolase (ACAA1; <a href="/entry/604054">604054</a>) were present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921319" 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>Wanders et al. (<a href="#21" class="mim-tip-reference" title="Wanders, R. J. A., van Roermund, C. W. T., Schelen, A., Schutgens, R. B. H., Tager, J. M., Stephenson, J. B. P., Clayton, P. T. &lt;strong&gt;A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities.&lt;/strong&gt; J. Inherit. Metab. Dis. 13: 375-379, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2122104/&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;2122104&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799399&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="2122104">1990</a>, <a href="#20" class="mim-tip-reference" title="Wanders, R. J. A., van Roermund, C. W. T., Brus, S., Schutgens, R. B. H., Tager, J. M., Jakobs, C. &lt;strong&gt;Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 385-388, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1357231/&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;1357231&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02435983&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="1357231">1992</a>) also described peroxisomal bifunctional enzyme deficiency, which was associated with a more severe phenotype than that of peroxisomal acyl-CoA oxidase deficiency. <a href="#20" class="mim-tip-reference" title="Wanders, R. J. A., van Roermund, C. W. T., Brus, S., Schutgens, R. B. H., Tager, J. M., Jakobs, C. &lt;strong&gt;Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 385-388, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1357231/&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;1357231&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02435983&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="1357231">Wanders et al. (1992)</a> used complementation analysis to identify the primary defect as residing in the bifunctional enzyme. The patient presented by <a href="#22" class="mim-tip-reference" title="Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., Jr., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E., Moser, H. W. &lt;strong&gt;Peroxisomal bifunctional enzyme deficiency.&lt;/strong&gt; J. Clin. Invest. 83: 771-777, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2921319/&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;2921319&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113956&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="2921319">Watkins et al. (1989)</a> lacked the L-bifunctional enzyme protein, whereas the patient reported by <a href="#21" class="mim-tip-reference" title="Wanders, R. J. A., van Roermund, C. W. T., Schelen, A., Schutgens, R. B. H., Tager, J. M., Stephenson, J. B. P., Clayton, P. T. &lt;strong&gt;A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities.&lt;/strong&gt; J. Inherit. Metab. Dis. 13: 375-379, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2122104/&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;2122104&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799399&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="2122104">Wanders et al. (1990)</a> had an inactive form of the enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2921319+1357231+2122104" 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 complementation analysis, <a href="#15" class="mim-tip-reference" title="Suzuki, Y., Shimozawa, N., Yajima, S., Tomatsu, S., Kondo, N., Nakada, Y., Akaboshi, S., Iai, M., Tanabe, Y., Hashimoto, T., Wanders, R. J. A., Schutgens, R. B. H., Moser, H. W., Orii, T. &lt;strong&gt;Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis.&lt;/strong&gt; Am. J. Hum. Genet. 54: 36-43, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8279468/&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;8279468&lt;/a&gt;]" pmid="8279468">Suzuki et al. (1994)</a> identified 2 unrelated Japanese girls with presumed L-bifunctional protein deficiency. One child showed profound hypotonia, feeding difficulty, and intractable convulsions soon after delivery. Craniofacial dysmorphism included large fontanel, frontal bossing, low nasal bridge and upward-slanting of palpebral fissures. Other features included hepatomegaly with normal transaminases and bilirubin, funnel chest, talipes equinovarus, and calcific stippling of the patella. She suffered a subdural hematoma due to vitamin K deficiency on the forty-ninth postnatal day and died of pneumonia at 12 months of age (<a href="#10" class="mim-tip-reference" title="Nakada, Y., Hyakuna, N., Suzuki, Y., Shimozawa, N., Takaesu, E., Ikema, R., Hirayama, K. &lt;strong&gt;A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein: comparison of two cases of Zellweger syndrome.&lt;/strong&gt; Brain Dev. 15: 453-456, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8147505/&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;8147505&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0387-7604(93)90087-o&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="8147505">Nakada et al., 1993</a>). The second child, born of consanguineous parents, showed scaphocephaly, frontal bossing, micrognathia, high-arched palate, delayed closure of the anterior fontanel, and calcific stippling at the shoulder and knee joints. She could smile and follow a person at 3 months of age, but regressed thereafter. She manifested adrenocortical insufficiency from the age of 11 months and died of airway obstruction at 21 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8279468+8147505" 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="#6" class="mim-tip-reference" title="Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J., Van Hoof, F. &lt;strong&gt;Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.&lt;/strong&gt; J. Pediat. 108: 25-32, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2868085/&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;2868085&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(86)80764-8&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="2868085">Goldfischer et al. (1986)</a> described an infant, 11 months old at the time of her sudden death, who showed clinical, biochemical, and pathologic features similar in many respects to those seen in the Zellweger syndrome. She had increased serum levels of very long chain fatty acids, an accumulation of trihydroxycoprostanoic acid in duodenal aspirate, and slightly increased levels of pipecolic acid concentrations in serum and urine. However, liver biopsy showed an abundance of peroxisomes, which are profoundly deficient in Zellweger syndrome. Furthermore, the activity of the peroxisomal enzyme acyl-CoA:dihydroxyacetone-phosphate acyltransferase was normal in the patient; this membrane-associated enzyme is deficient in Zellweger syndrome. Peroxisomal oxidation of palmitoyl-CoA was reduced about 15% of the control values, suggesting a defect in peroxisomal beta-oxidation. In this patient, <a href="#13" class="mim-tip-reference" title="Schram, A. W., Goldfischer, S., van Roermund, C. W. T., Brouwer-Kelder, E. M., Collins, J., Hashimoto, T., Heymans, H. S. A., van den Bosch, H., Schutgens, R. B. H., Tager, J. M., Wanders, R. J. A. &lt;strong&gt;Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.&lt;/strong&gt; Proc. Nat. Acad. Sci. 84: 2494-2496, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2882519/&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;2882519&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.84.8.2494&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="2882519">Schram et al. (1987)</a> found deficiency of peroxisomal 3-oxoacyl-CoA thiolase in postmortem liver. <a href="#1" class="mim-tip-reference" title="Clayton, P. T., Patel, E., Lawson, A. M., Carruthers, R. A., Collins, J. &lt;strong&gt;Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.&lt;/strong&gt; J. Clin. Invest. 85: 1267-1273, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2318981/&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;2318981&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI114563&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="2318981">Clayton et al. (1990)</a> demonstrated that unconjugated varanic acid (3-alpha,7-alpha,12-alpha,24-tetrahydroxycholestanoic acid), an intermediate in the formation of cholic acid from THCA (3-alpha,7-alpha,12-alpha-trihydroxycholestanoic acid), was present in the body fluids of the patient reported by <a href="#6" class="mim-tip-reference" title="Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J., Van Hoof, F. &lt;strong&gt;Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.&lt;/strong&gt; J. Pediat. 108: 25-32, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2868085/&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;2868085&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(86)80764-8&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="2868085">Goldfischer et al. (1986)</a>. In a reinvestigation of the patient reported by <a href="#6" class="mim-tip-reference" title="Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J., Van Hoof, F. &lt;strong&gt;Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.&lt;/strong&gt; J. Pediat. 108: 25-32, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2868085/&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;2868085&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(86)80764-8&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="2868085">Goldfischer et al. (1986)</a>, <a href="#3" class="mim-tip-reference" title="Ferdinandusse, S., van Grunsven, E. G., Oostheim, W., Denis, S., Hogenhout, E. M., Ijlst, L., van Roermund, C. W. T., Waterham, H. R., Goldfischer, S., Wanders, R. J. A. &lt;strong&gt;Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of D-bifunctional protein.&lt;/strong&gt; Am. J. Hum. Genet. 70: 1589-1593, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11992265/&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;11992265&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11992265[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/10.1086/340970&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="11992265">Ferdinandusse et al. (2002)</a> found absence of the D-bifunctional protein postmortem brain, whereas thiolase was normally present. In this patient, <a href="#3" class="mim-tip-reference" title="Ferdinandusse, S., van Grunsven, E. G., Oostheim, W., Denis, S., Hogenhout, E. M., Ijlst, L., van Roermund, C. W. T., Waterham, H. R., Goldfischer, S., Wanders, R. J. A. &lt;strong&gt;Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of D-bifunctional protein.&lt;/strong&gt; Am. J. Hum. Genet. 70: 1589-1593, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11992265/&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;11992265&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11992265[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/10.1086/340970&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="11992265">Ferdinandusse et al. (2002)</a> identified a homozygous mutation in the HSD17B4 gene (<a href="/entry/601860#0006">601860.0006</a>), confirming a diagnosis of D-bifunctional protein deficiency. There was no longer evidence for the existence of thiolase deficiency as a distinct clinical entity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2882519+2318981+2868085+11992265" 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="#17" class="mim-tip-reference" title="van Grunsven, E. G., van Berkel, E., Ijlst, L., Vreken, P., de Klerk, J. B. C., Adamski, J., Lemonde, H., Clayton, P. T., Cuebas, D. A., Wanders, R. J. A. &lt;strong&gt;Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency.&lt;/strong&gt; Proc. Nat. Acad. Sci. 95: 2128-2133, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9482850/&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;9482850&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.95.5.2128&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="9482850">Van Grunsven et al. (1998)</a> reported a boy with D-bifunctional protein deficiency confirmed by the demonstration of a homozygous mutation in the HSD17B4 gene (<a href="/entry/601860#0003">601860.0003</a>). The boy was born of nonconsanguineous Caucasian parents at 36 weeks' gestation after an uncomplicated pregnancy. Head circumference was at the 50th percentile at birth, but macrocephaly developed during the first year of life. Examination showed high forehead with frontal bossing, low-set ears, and a large fontanel. The liver was palpable 2.5 cm below the costal margin. Other features included a long, small thorax, hypospadias, limb-girdle muscle wasting, and generalized hypotonia. Neurologic examination showed negative traction and Moro response, with maximal headlag at 4 weeks. At the age of 2 months, the patient became cyanotic and developed epileptic seizures leading to aspiration. MRI of the brain showed white matter abnormalities consistent with dysmyelination. The patient died at the age of 16 months from aspiration pneumonia. Laboratory studies showed increased plasma very long-chain fatty acids increased levels of several bile acid intermediates, and normal levels of plasmalogen. The 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely inactive, whereas the enoyl-CoA hydratase component was active. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482850" 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="Nakano, K., Zhang, Z., Shimozawa, N., Kondo, N., Ishii, N., Funatsuka, M., Shirakawa, S., Itoh, M., Takashima, S., Une, M., Kana-aki, R. R., Mukai, K., Osawa, M., Suzuki, Y. &lt;strong&gt;D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes.&lt;/strong&gt; J. Pediat. 139: 865-867, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11743515/&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;11743515&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.119170&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="11743515">Nakano et al. (2001)</a> reported a patient with D-bifunctional protein deficiency who was compound heterozygous for 2 mutations in the HSD17B4 gene (<a href="/entry/601860#0001">601860.0001</a> and <a href="/entry/601860#0005">601860.0005</a>). Polyhydramnios and fetal ascites were detected at 30 weeks' gestation. At birth, the child had claw hands, hammertoes, abdominal distention, generalized hypotonia, and craniofacial dysmorphism with frontal bossing, low nasal bridge, and large fontanel. Chylous ascites was aspirated on the eighth day of life. Postnatally she developed psychomotor retardation. She died of pneumonia and heart failure at 7 months of age. Autopsy showed polymicrogyria of the cerebrum and cerebellum, a single neuron heterotopia in the white matter, hypoplastic corpus callosum, excessive convolutions of the inferior olivary nucleus, fibrosis around the Glisson capsule in the liver, renal cortical microcysts involving the Bowman capsule, and lamellar inclusions in the adrenal cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11743515" 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="#2" class="mim-tip-reference" title="Ferdinandusse, S., Denis, S., Mooyer, P. A. W., Dekker, C., Duran, M., Soorani-Lunsing, R. J., Boltshauser, E., Macaya, A., Gartner, J., Majoie, C. B. L. M., Barth, P. G., Wanders, R. J. A., Poll-The, B. T. &lt;strong&gt;Clinical and biochemical spectrum of D-bifunctional protein deficiency.&lt;/strong&gt; Ann. Neurol. 59: 92-104, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16278854/&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;16278854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20702&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="16278854">Ferdinandusse et al. (2006)</a> reported the clinical features of 126 patients with D-bifunctional protein deficiency. Some of the patients had been previously reported. Most patients presented with neonatal hypotonia and seizures. Other common features included visual impairment, severe psychomotor retardation, and a characteristic facies with high forehead, high-arched palate, enlarged fontanel, long philtrum, epicanthal folds, hypertelorism, macrocephaly, retrognathia, and low-set ears. Brain imaging showed gross ventricular dilatation (29%), neocortical dysplasia (27%), cerebral demyelination (17%), and cerebellar atrophy (17%). Liver disease was present in 26% of patients and 43% had hepatomegaly. Postmortem examination of 11 patients showed polymicrogyria in 64%. Renal cysts and adrenal cortex atrophy were seen in 33% and 42% of autopsied cases, respectively, and uncommon features included delay of bone maturation, skeletal malformations, and calcific stippling. Although most patients died before age 2 years, 12 patients survived beyond 2 years, 5 of whom survived beyond 7.5 years. Biochemical analysis showed a clear correlation between peroxisomal beta-oxidation activity and survival. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278854" 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>
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<p>DBP deficiency can be divided into 3 types, depending on which enzymatic activity is deficient: (1) type I-deficient patients have a deficiency of both the hydratase and dehydrogenase units of DBP (in fibroblasts of almost all type I-deficient patients, no DBP protein can be detected by immunoblotting with an antibody against human DBP); (2) type II-deficient patients have an isolated deficiency of the hydratase unit; and (3) type III-deficient patients have an isolated deficiency of the dehydrogenase unit (<a href="#19" class="mim-tip-reference" title="Wanders, R. J. A., Barth, P. G., Heymans, H. S. A. &lt;strong&gt;Single peroxisomal enzyme deficiencies.In: Scriver C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Molecular and Metabolic Bases of Inherited Disease.&lt;/strong&gt; McGraw-Hill, New York 2001. Pp. 3219-3256."None>Wanders et al., 2001</a>). This classification can be made on the basis of enzyme activity measurements in combination with mutation analysis, as described by <a href="#5" class="mim-tip-reference" title="Gloerich, J., Denis, S., Van Grunsven, E. G., Dacremont, G., Wanders, R. J., Ferdinandusse, S. &lt;strong&gt;A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency.&lt;/strong&gt; J. Lipid Res. 44: 640-644, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12562856/&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;12562856&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1194/jlr.D200039-JLR200&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="12562856">Gloerich et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12562856" 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>
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<p>The diagnosis of DBP deficiency is commonly made based on the accumulation of very long chain fatty acids (VLCFA), dihydroxy- and trihydroxycholestanoic acid (DHCA and THCA), and pristanic and phytanic acid in plasma. However, some patients with residual enzyme activity may not have abnormal plasma values, making the diagnosis difficult. <a href="#7" class="mim-tip-reference" title="Gronborg, S., Kratzner, R., Spiegler, J., Ferdinandusse, S., Wanders, R. J. A., Waterham, H. R., Gartner, J. &lt;strong&gt;Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.&lt;/strong&gt; Am. J. Med. Genet. 152A: 2845-2849, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20949532/&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;20949532&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33677&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="20949532">Gronborg et al. (2010)</a> reported 2 sibs with the disorder who were initially found to have normal VLCFA plasma values when studied based on clinical features. Features included neonatal hypotonia, early-onset seizures, and severe developmental delay. Both also had hearing loss and showed developmental regression at about age 4 years. The older sib died at age 10 years, 9 months, without correct diagnosis. Brain MRI in the 2 sibs at ages 28 and 30 months, respectively, showed typical findings of a peroxisomal disorder, prompting repeated plasma examination in the younger sib and studies of patient fibroblasts, which led to proper molecular diagnosis. The MRI findings included leukoencephalopathy of cerebral and cerebellar white matter, polymicrogyria, and pachygyria. <a href="#7" class="mim-tip-reference" title="Gronborg, S., Kratzner, R., Spiegler, J., Ferdinandusse, S., Wanders, R. J. A., Waterham, H. R., Gartner, J. &lt;strong&gt;Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.&lt;/strong&gt; Am. J. Med. Genet. 152A: 2845-2849, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20949532/&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;20949532&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33677&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="20949532">Gronborg et al. (2010)</a> concluded that brain MRI may aid in the diagnosis of patients with DBP deficiency, particularly in cases with no or mild plasma abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20949532" 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>Prenatal Diagnosis</em></strong></p><p>
<a href="#16" class="mim-tip-reference" title="Suzuki, Y., Zhang, Z., Shimozawa, N., Muro, M., Shono, H., Toda, S., Miyahara, S., Hashimoto, T., Usuda, N., Ito, M., Takashima, S., Kondo, N. &lt;strong&gt;Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency.&lt;/strong&gt; J. Hum. Genet. 44: 143-147, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10319576/&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;10319576&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s100380050131&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="10319576">Suzuki et al. (1999)</a> reported the first successful prenatal diagnosis of D-bifunctional protein deficiency using cultured amniocytes obtained from a fetus at 16 weeks' gestation. These authors used several methods, including an assay for lignoceric acid oxidation activity, indirect immunofluorescence staining and immunoblot analysis for the presence of DBP, and genetic analysis using RT-PCR. After pregnancy termination, immunohistochemical and biochemical studies of the fetus confirmed their prenatal diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10319576" 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>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>In 2 Japanese patients reported by <a href="#15" class="mim-tip-reference" title="Suzuki, Y., Shimozawa, N., Yajima, S., Tomatsu, S., Kondo, N., Nakada, Y., Akaboshi, S., Iai, M., Tanabe, Y., Hashimoto, T., Wanders, R. J. A., Schutgens, R. B. H., Moser, H. W., Orii, T. &lt;strong&gt;Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis.&lt;/strong&gt; Am. J. Hum. Genet. 54: 36-43, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8279468/&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;8279468&lt;/a&gt;]" pmid="8279468">Suzuki et al. (1994)</a> as having L-bifunctional protein deficiency, <a href="#14" class="mim-tip-reference" title="Suzuki, Y., Jiang, L. L., Souri, M., Miyazawa, S., Fukuda, S., Zhang, Z., Une, M., Shimozawa, N., Kondo, N., Orii, T., Hashimoto, T. &lt;strong&gt;D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1153-1162, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9345094/&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;9345094&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301599&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="9345094">Suzuki et al. (1997)</a> identified 2 different homozygous deletions in the HSD17B4 gene (<a href="/entry/601860#0001">601860.0001</a>; <a href="/entry/601860#0002">601860.0002</a>), confirming D-bifunctional protein deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9345094+8279468" 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 9 patients who carried the diagnosis of L-bifunctional protein deficiency on the basis of complementation analysis, <a href="#18" class="mim-tip-reference" title="van Grunsven, E. G., van Berkel, E., Mooijer, P. A. W., Watkins, P. A., Moser, H. W., Suzuki, Y., Jiang, L. L., Hashimoto, T., Hoefler, G., Adamski, J., Wanders, R. J. A. &lt;strong&gt;Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis.&lt;/strong&gt; Am. J. Hum. Genet. 64: 99-107, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9915948/&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;9915948&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302180&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="9915948">van Grunsven et al. (1999)</a> identified mutations in the HSD17B4 gene, confirming a diagnosis of D-bifunctional protein deficiency. Four of the 9 patients had the same mutation (<a href="/entry/601860#0003">601860.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9915948" 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 D-bifunctional protein deficiency originally reported by <a href="#22" class="mim-tip-reference" title="Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., Jr., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E., Moser, H. W. &lt;strong&gt;Peroxisomal bifunctional enzyme deficiency.&lt;/strong&gt; J. Clin. Invest. 83: 771-777, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2921319/&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;2921319&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113956&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="2921319">Watkins et al. (1989)</a>, <a href="#18" class="mim-tip-reference" title="van Grunsven, E. G., van Berkel, E., Mooijer, P. A. W., Watkins, P. A., Moser, H. W., Suzuki, Y., Jiang, L. L., Hashimoto, T., Hoefler, G., Adamski, J., Wanders, R. J. A. &lt;strong&gt;Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis.&lt;/strong&gt; Am. J. Hum. Genet. 64: 99-107, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9915948/&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;9915948&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302180&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="9915948">van Grunsven et al. (1999)</a> identified a homozygous 2-bp deletion in the HSD17B4 gene (<a href="/entry/601860#0007">601860.0007</a>). The patient was originally thought to have L-bifunctional protein deficiency based on immunoblot analysis of postmortem liver tissue. However, reanalysis showed accumulation of both very long chain fatty acids and bile acid intermediates, which was hard to reconcile with an isolated deficiency of the L-bifunctional protein. The results suggested that most, if not all, patients whose peroxisomal disorder had been diagnosed as L-bifunctional protein deficiency were in fact cases of D-bifunctional protein deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2921319+9915948" 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="Ferdinandusse, S., Ylianttila, M. S., Gloerich, J., Koski, M. K., Oostheim, W., Waterham, H. R., Hiltunen, J. K., Wanders, R. J. A., Glumoff, T. &lt;strong&gt;Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.&lt;/strong&gt; Am. J. Hum. Genet. 78: 112-124, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16385454/&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;16385454&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16385454[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/10.1086/498880&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="16385454">Ferdinandusse et al. (2006)</a> reported the mutational spectrum of DBP deficiency on the basis of molecular analysis in 110 patients. They identified 61 different mutations by DBP cDNA analysis, 48 of which had not been previously reported. The predicted effects of the different disease-causing amino acid changes in protein structure were determined using the crystal structures. The effects ranged from the replacement of catalytic amino acid residues or residues in direct contact with the substrate or cofactor to disturbances of protein folding or dimerization of the subunits. To study whether there is a genotype-phenotype correlation for DBP deficiency, these structure-based analyses were combined with extensive biochemical analyses of patient material (cultured skin fibroblasts and plasma) and available clinical information on the patients. They found that the effect of the mutations identified in patients with a relatively mild clinical and biochemical presentation was less detrimental to the protein structure than the effect of mutations identified in those with a very severe presentation. These results suggested that the amount of residual DBP activity correlates with the severity of the phenotype. Thus the data indicated that on the basis of the predicted effect of mutations on protein structure, a genotype-phenotype correlation exists for DBP deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16385454" 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>
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<a id="populationGenetics" class="mim-anchor"></a>
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<strong>Population Genetics</strong>
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<p>DBP deficiency has an estimated prevalence of 1 in 100,000 (<a href="#2" class="mim-tip-reference" title="Ferdinandusse, S., Denis, S., Mooyer, P. A. W., Dekker, C., Duran, M., Soorani-Lunsing, R. J., Boltshauser, E., Macaya, A., Gartner, J., Majoie, C. B. L. M., Barth, P. G., Wanders, R. J. A., Poll-The, B. T. &lt;strong&gt;Clinical and biochemical spectrum of D-bifunctional protein deficiency.&lt;/strong&gt; Ann. Neurol. 59: 92-104, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16278854/&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;16278854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20702&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="16278854">Ferdinandusse et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278854" 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>
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<a id="seeAlso" class="mim-anchor"></a>
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<strong>See Also:</strong>
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<span class="mim-text-font">
<a href="#Naidu1988" class="mim-tip-reference" title="Naidu, S., Hoefler, G., Watkins, P. A., Chen, W. W., Moser, A. B., Hoefler, S., Rance, N. E., Powers, J. M., Beard, M., Green, W. R., Hashimoto, T., Moser, H. W. &lt;strong&gt;Neonatal seizures and retardation in a female with biochemical features of X-linked adrenoleukodystrophy: a possible new peroxisomal disease entity.&lt;/strong&gt; Neurology 38: 1100-1107, 1988.">Naidu et al. (1988)</a>
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<a id="references"class="mim-anchor"></a>
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<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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</h4>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="1" class="mim-anchor"></a>
<a id="Clayton1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clayton, P. T., Patel, E., Lawson, A. M., Carruthers, R. A., Collins, J.
<strong>Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.</strong>
J. Clin. Invest. 85: 1267-1273, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2318981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2318981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2318981" 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/JCI114563" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Ferdinandusse2006" class="mim-anchor"></a>
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<p class="mim-text-font">
Ferdinandusse, S., Denis, S., Mooyer, P. A. W., Dekker, C., Duran, M., Soorani-Lunsing, R. J., Boltshauser, E., Macaya, A., Gartner, J., Majoie, C. B. L. M., Barth, P. G., Wanders, R. J. A., Poll-The, B. T.
<strong>Clinical and biochemical spectrum of D-bifunctional protein deficiency.</strong>
Ann. Neurol. 59: 92-104, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278854" 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.20702" target="_blank">Full Text</a>]
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<a id="Ferdinandusse2002" class="mim-anchor"></a>
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Ferdinandusse, S., van Grunsven, E. G., Oostheim, W., Denis, S., Hogenhout, E. M., Ijlst, L., van Roermund, C. W. T., Waterham, H. R., Goldfischer, S., Wanders, R. J. A.
<strong>Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of D-bifunctional protein.</strong>
Am. J. Hum. Genet. 70: 1589-1593, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992265</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992265[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=11992265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/340970" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
<a id="Ferdinandusse2006" class="mim-anchor"></a>
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<p class="mim-text-font">
Ferdinandusse, S., Ylianttila, M. S., Gloerich, J., Koski, M. K., Oostheim, W., Waterham, H. R., Hiltunen, J. K., Wanders, R. J. A., Glumoff, T.
<strong>Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.</strong>
Am. J. Hum. Genet. 78: 112-124, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16385454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16385454</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16385454[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=16385454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/498880" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
<a id="Gloerich2003" class="mim-anchor"></a>
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<p class="mim-text-font">
Gloerich, J., Denis, S., Van Grunsven, E. G., Dacremont, G., Wanders, R. J., Ferdinandusse, S.
<strong>A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency.</strong>
J. Lipid Res. 44: 640-644, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12562856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12562856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12562856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1194/jlr.D200039-JLR200" target="_blank">Full Text</a>]
</p>
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<a id="Goldfischer1986" class="mim-anchor"></a>
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Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J., Van Hoof, F.
<strong>Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.</strong>
J. Pediat. 108: 25-32, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2868085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2868085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2868085" 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(86)80764-8" target="_blank">Full Text</a>]
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<a id="Gronborg2010" class="mim-anchor"></a>
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<p class="mim-text-font">
Gronborg, S., Kratzner, R., Spiegler, J., Ferdinandusse, S., Wanders, R. J. A., Waterham, H. R., Gartner, J.
<strong>Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.</strong>
Am. J. Med. Genet. 152A: 2845-2849, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20949532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20949532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20949532" 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.a.33677" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
<a id="McMillan2012" class="mim-anchor"></a>
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<p class="mim-text-font">
McMillan, H. J., Worthylake, T., Schwartzentruber, J., Gottlieb, C. C., Lawrence, S. E., MacKenzie, A., Beaulieu, C. L., Mooyer, P. A. W., FORGE Canada Consortium, Wanders, R. J. A., Majewski, J., Bulman, D. E., Geraghty, M. T., Ferdinandusse, S., Boycott, K. M.
<strong>Specific combination of compound heterozygous mutations in 17-beta-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency.</strong>
Orphanet J. Rare Dis. 7: 90, 2012. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23181892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23181892</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23181892[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=23181892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1186/1750-1172-7-90" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Naidu1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naidu, S., Hoefler, G., Watkins, P. A., Chen, W. W., Moser, A. B., Hoefler, S., Rance, N. E., Powers, J. M., Beard, M., Green, W. R., Hashimoto, T., Moser, H. W.
<strong>Neonatal seizures and retardation in a female with biochemical features of X-linked adrenoleukodystrophy: a possible new peroxisomal disease entity.</strong>
Neurology 38: 1100-1107, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3386829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3386829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3386829" 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.38.7.1100" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Nakada1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nakada, Y., Hyakuna, N., Suzuki, Y., Shimozawa, N., Takaesu, E., Ikema, R., Hirayama, K.
<strong>A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein: comparison of two cases of Zellweger syndrome.</strong>
Brain Dev. 15: 453-456, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8147505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8147505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8147505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0387-7604(93)90087-o" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Nakano2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nakano, K., Zhang, Z., Shimozawa, N., Kondo, N., Ishii, N., Funatsuka, M., Shirakawa, S., Itoh, M., Takashima, S., Une, M., Kana-aki, R. R., Mukai, K., Osawa, M., Suzuki, Y.
<strong>D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes.</strong>
J. Pediat. 139: 865-867, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11743515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11743515</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11743515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1067/mpd.2001.119170" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Pierce2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pierce, S. B., Walsh, T., Chisholm, K. M., Lee, M, K., Thornton, A. M., Fiumara, A., Opitz, J. M., Levy-Lahad, E., Klevit, R. E., King, M.-C.
<strong>Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome.</strong>
Am. J. Hum. Genet. 87: 282-288, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20673864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20673864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20673864[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=20673864" 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.ajhg.2010.07.007" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Schram1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schram, A. W., Goldfischer, S., van Roermund, C. W. T., Brouwer-Kelder, E. M., Collins, J., Hashimoto, T., Heymans, H. S. A., van den Bosch, H., Schutgens, R. B. H., Tager, J. M., Wanders, R. J. A.
<strong>Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.</strong>
Proc. Nat. Acad. Sci. 84: 2494-2496, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2882519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2882519</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2882519" 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.84.8.2494" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Suzuki1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Suzuki, Y., Jiang, L. L., Souri, M., Miyazawa, S., Fukuda, S., Zhang, Z., Une, M., Shimozawa, N., Kondo, N., Orii, T., Hashimoto, T.
<strong>D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.</strong>
Am. J. Hum. Genet. 61: 1153-1162, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345094</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/301599" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Suzuki1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Suzuki, Y., Shimozawa, N., Yajima, S., Tomatsu, S., Kondo, N., Nakada, Y., Akaboshi, S., Iai, M., Tanabe, Y., Hashimoto, T., Wanders, R. J. A., Schutgens, R. B. H., Moser, H. W., Orii, T.
<strong>Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis.</strong>
Am. J. Hum. Genet. 54: 36-43, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8279468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8279468</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8279468" 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="16" class="mim-anchor"></a>
<a id="Suzuki1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Suzuki, Y., Zhang, Z., Shimozawa, N., Muro, M., Shono, H., Toda, S., Miyahara, S., Hashimoto, T., Usuda, N., Ito, M., Takashima, S., Kondo, N.
<strong>Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency.</strong>
J. Hum. Genet. 44: 143-147, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10319576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10319576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10319576" 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/s100380050131" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="van Grunsven1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van Grunsven, E. G., van Berkel, E., Ijlst, L., Vreken, P., de Klerk, J. B. C., Adamski, J., Lemonde, H., Clayton, P. T., Cuebas, D. A., Wanders, R. J. A.
<strong>Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency.</strong>
Proc. Nat. Acad. Sci. 95: 2128-2133, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9482850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9482850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482850" 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.95.5.2128" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="18" class="mim-anchor"></a>
<a id="van Grunsven1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van Grunsven, E. G., van Berkel, E., Mooijer, P. A. W., Watkins, P. A., Moser, H. W., Suzuki, Y., Jiang, L. L., Hashimoto, T., Hoefler, G., Adamski, J., Wanders, R. J. A.
<strong>Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis.</strong>
Am. J. Hum. Genet. 64: 99-107, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9915948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9915948</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9915948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302180" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Wanders2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wanders, R. J. A., Barth, P. G., Heymans, H. S. A.
<strong>Single peroxisomal enzyme deficiencies.In: Scriver C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Molecular and Metabolic Bases of Inherited Disease.</strong>
McGraw-Hill, New York 2001. Pp. 3219-3256.
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Wanders1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wanders, R. J. A., van Roermund, C. W. T., Brus, S., Schutgens, R. B. H., Tager, J. M., Jakobs, C.
<strong>Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis.</strong>
J. Inherit. Metab. Dis. 15: 385-388, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357231</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1357231" 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/BF02435983" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Wanders1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wanders, R. J. A., van Roermund, C. W. T., Schelen, A., Schutgens, R. B. H., Tager, J. M., Stephenson, J. B. P., Clayton, P. T.
<strong>A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities.</strong>
J. Inherit. Metab. Dis. 13: 375-379, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2122104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2122104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2122104" 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/BF01799399" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Watkins1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., Jr., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E., Moser, H. W.
<strong>Peroxisomal bifunctional enzyme deficiency.</strong>
J. Clin. Invest. 83: 771-777, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921319</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921319" 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/JCI113956" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Watkins1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Watkins, P. A., McGuinness, M. C., Raymond, G. V., Hicks, B. A., Sisk, J. M., Moser, A. B., Moser, H. W.
<strong>Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies.</strong>
Ann. Neurol. 38: 472-477, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668838" 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.410380322" target="_blank">Full Text</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">
Cassandra L. Kniffin - updated : 6/4/2014
</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">
Cassandra L. Kniffin - updated : 3/26/2012<br>Marla J. F. O'Neill - updated : 2/24/2011<br>Victor A. McKusick - updated : 5/4/2006<br>Cassandra L. Kniffin - updated : 5/3/2006<br>Cassandra L. Kniffin - reorganized : 12/8/2005<br>Cassandra L. Kniffin - updated : 12/7/2005<br>Victor A. McKusick - updated : 11/26/1997
</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">
Victor A. McKusick : 3/18/1994
</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">
alopez : 06/16/2014
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<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">
mcolton : 6/5/2014<br>ckniffin : 6/4/2014<br>alopez : 10/25/2012<br>alopez : 3/30/2012<br>terry : 3/28/2012<br>ckniffin : 3/26/2012<br>wwang : 2/25/2011<br>terry : 2/24/2011<br>wwang : 4/13/2007<br>carol : 1/2/2007<br>alopez : 5/4/2006<br>wwang : 5/3/2006<br>ckniffin : 5/3/2006<br>carol : 12/8/2005<br>ckniffin : 12/7/2005<br>ckniffin : 12/7/2005<br>carol : 11/30/2005<br>carol : 11/30/2005<br>alopez : 10/30/2002<br>alopez : 6/17/2002<br>alopez : 6/17/2002<br>alopez : 6/17/2002<br>alopez : 6/17/2002<br>alopez : 6/14/2002<br>carol : 3/30/1999<br>carol : 2/17/1999<br>terry : 7/24/1998<br>terry : 12/4/1997<br>terry : 12/3/1997<br>terry : 11/26/1997<br>terry : 1/27/1995<br>warfield : 3/31/1994<br>carol : 3/18/1994
</span>
</div>
</div>
</div>
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</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> 261515
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
D-BIFUNCTIONAL PROTEIN DEFICIENCY
</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">
17-BETA-HYDROXYSTEROID DEHYDROGENASE IV DEFICIENCY<br />
DBP DEFICIENCY<br />
PEROXISOMAL BIFUNCTIONAL ENZYME DEFICIENCY<br />
PBFE DEFICIENCY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 238068007; &nbsp;
<strong>ORPHA:</strong> 300; &nbsp;
<strong>DO:</strong> 0090031; &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">
5q23.1
</span>
</td>
<td>
<span class="mim-font">
D-bifunctional protein deficiency
</span>
</td>
<td>
<span class="mim-font">
261515
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
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3
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HSD17B4
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<span class="mim-font">
601860
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<h4>
<span class="mim-font">
<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because D-bifunctional protein deficiency can be caused by homozygous or compound heterozygous mutation in the HSD17B4 gene (601860) on chromosome 5q2, which encodes the D-bifunctional protein (DBP).</p>
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<span class="mim-font">
<strong>Description</strong>
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<p>D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). </p><p>DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed. </p>
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<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
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<p>Watkins et al. (1989) reported a black male infant with neonatal hypotonia and macrocephaly who developed seizures and required ventilatory support for the first 4 days of life. By 6 weeks of age, he had made no developmental progress, seizures continued, and the fontanels were large. Brain biopsy at 6 weeks of age showed polymicrogyria. He also had generalized osteopenia with delayed bone maturation. He died at 5.5 months as a result of an acute necrotizing enterocolitis. Postmortem examination showed small adrenal glands with a normal medulla and replacement of the entire cortex with a single type of lipid-containing 'balloon' cell. The changes were identical to those of seen in X-linked and autosomal recessive neonatal forms of adrenoleukodystrophy. Very long-chain fatty acids were increased in the patient's plasma and fibroblasts, and beta-oxidation was impaired. However, biochemical analysis distinguished the disorder from the other forms of ALD: cultured fibroblasts had normal levels of serum phytanic acid and L-pipecolic acid and normal plasmalogen synthesis. In addition, electron microscopy and catalase subcellular distribution studies showed that peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes showed deficiency of the L-bifunctional enzyme (LBP; enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase; 607037), whereas acyl-CoA oxidase and the mature form of peroxisomal 3-oxoacyl-CoA thiolase (ACAA1; 604054) were present. </p><p>Wanders et al. (1990, 1992) also described peroxisomal bifunctional enzyme deficiency, which was associated with a more severe phenotype than that of peroxisomal acyl-CoA oxidase deficiency. Wanders et al. (1992) used complementation analysis to identify the primary defect as residing in the bifunctional enzyme. The patient presented by Watkins et al. (1989) lacked the L-bifunctional enzyme protein, whereas the patient reported by Wanders et al. (1990) had an inactive form of the enzyme. </p><p>Using complementation analysis, Suzuki et al. (1994) identified 2 unrelated Japanese girls with presumed L-bifunctional protein deficiency. One child showed profound hypotonia, feeding difficulty, and intractable convulsions soon after delivery. Craniofacial dysmorphism included large fontanel, frontal bossing, low nasal bridge and upward-slanting of palpebral fissures. Other features included hepatomegaly with normal transaminases and bilirubin, funnel chest, talipes equinovarus, and calcific stippling of the patella. She suffered a subdural hematoma due to vitamin K deficiency on the forty-ninth postnatal day and died of pneumonia at 12 months of age (Nakada et al., 1993). The second child, born of consanguineous parents, showed scaphocephaly, frontal bossing, micrognathia, high-arched palate, delayed closure of the anterior fontanel, and calcific stippling at the shoulder and knee joints. She could smile and follow a person at 3 months of age, but regressed thereafter. She manifested adrenocortical insufficiency from the age of 11 months and died of airway obstruction at 21 months of age. </p><p>Goldfischer et al. (1986) described an infant, 11 months old at the time of her sudden death, who showed clinical, biochemical, and pathologic features similar in many respects to those seen in the Zellweger syndrome. She had increased serum levels of very long chain fatty acids, an accumulation of trihydroxycoprostanoic acid in duodenal aspirate, and slightly increased levels of pipecolic acid concentrations in serum and urine. However, liver biopsy showed an abundance of peroxisomes, which are profoundly deficient in Zellweger syndrome. Furthermore, the activity of the peroxisomal enzyme acyl-CoA:dihydroxyacetone-phosphate acyltransferase was normal in the patient; this membrane-associated enzyme is deficient in Zellweger syndrome. Peroxisomal oxidation of palmitoyl-CoA was reduced about 15% of the control values, suggesting a defect in peroxisomal beta-oxidation. In this patient, Schram et al. (1987) found deficiency of peroxisomal 3-oxoacyl-CoA thiolase in postmortem liver. Clayton et al. (1990) demonstrated that unconjugated varanic acid (3-alpha,7-alpha,12-alpha,24-tetrahydroxycholestanoic acid), an intermediate in the formation of cholic acid from THCA (3-alpha,7-alpha,12-alpha-trihydroxycholestanoic acid), was present in the body fluids of the patient reported by Goldfischer et al. (1986). In a reinvestigation of the patient reported by Goldfischer et al. (1986), Ferdinandusse et al. (2002) found absence of the D-bifunctional protein postmortem brain, whereas thiolase was normally present. In this patient, Ferdinandusse et al. (2002) identified a homozygous mutation in the HSD17B4 gene (601860.0006), confirming a diagnosis of D-bifunctional protein deficiency. There was no longer evidence for the existence of thiolase deficiency as a distinct clinical entity. </p><p>Van Grunsven et al. (1998) reported a boy with D-bifunctional protein deficiency confirmed by the demonstration of a homozygous mutation in the HSD17B4 gene (601860.0003). The boy was born of nonconsanguineous Caucasian parents at 36 weeks' gestation after an uncomplicated pregnancy. Head circumference was at the 50th percentile at birth, but macrocephaly developed during the first year of life. Examination showed high forehead with frontal bossing, low-set ears, and a large fontanel. The liver was palpable 2.5 cm below the costal margin. Other features included a long, small thorax, hypospadias, limb-girdle muscle wasting, and generalized hypotonia. Neurologic examination showed negative traction and Moro response, with maximal headlag at 4 weeks. At the age of 2 months, the patient became cyanotic and developed epileptic seizures leading to aspiration. MRI of the brain showed white matter abnormalities consistent with dysmyelination. The patient died at the age of 16 months from aspiration pneumonia. Laboratory studies showed increased plasma very long-chain fatty acids increased levels of several bile acid intermediates, and normal levels of plasmalogen. The 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely inactive, whereas the enoyl-CoA hydratase component was active. </p><p>Nakano et al. (2001) reported a patient with D-bifunctional protein deficiency who was compound heterozygous for 2 mutations in the HSD17B4 gene (601860.0001 and 601860.0005). Polyhydramnios and fetal ascites were detected at 30 weeks' gestation. At birth, the child had claw hands, hammertoes, abdominal distention, generalized hypotonia, and craniofacial dysmorphism with frontal bossing, low nasal bridge, and large fontanel. Chylous ascites was aspirated on the eighth day of life. Postnatally she developed psychomotor retardation. She died of pneumonia and heart failure at 7 months of age. Autopsy showed polymicrogyria of the cerebrum and cerebellum, a single neuron heterotopia in the white matter, hypoplastic corpus callosum, excessive convolutions of the inferior olivary nucleus, fibrosis around the Glisson capsule in the liver, renal cortical microcysts involving the Bowman capsule, and lamellar inclusions in the adrenal cortex. </p><p>Ferdinandusse et al. (2006) reported the clinical features of 126 patients with D-bifunctional protein deficiency. Some of the patients had been previously reported. Most patients presented with neonatal hypotonia and seizures. Other common features included visual impairment, severe psychomotor retardation, and a characteristic facies with high forehead, high-arched palate, enlarged fontanel, long philtrum, epicanthal folds, hypertelorism, macrocephaly, retrognathia, and low-set ears. Brain imaging showed gross ventricular dilatation (29%), neocortical dysplasia (27%), cerebral demyelination (17%), and cerebellar atrophy (17%). Liver disease was present in 26% of patients and 43% had hepatomegaly. Postmortem examination of 11 patients showed polymicrogyria in 64%. Renal cysts and adrenal cortex atrophy were seen in 33% and 42% of autopsied cases, respectively, and uncommon features included delay of bone maturation, skeletal malformations, and calcific stippling. Although most patients died before age 2 years, 12 patients survived beyond 2 years, 5 of whom survived beyond 7.5 years. Biochemical analysis showed a clear correlation between peroxisomal beta-oxidation activity and survival. </p>
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<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
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<span class="mim-text-font">
<p>DBP deficiency can be divided into 3 types, depending on which enzymatic activity is deficient: (1) type I-deficient patients have a deficiency of both the hydratase and dehydrogenase units of DBP (in fibroblasts of almost all type I-deficient patients, no DBP protein can be detected by immunoblotting with an antibody against human DBP); (2) type II-deficient patients have an isolated deficiency of the hydratase unit; and (3) type III-deficient patients have an isolated deficiency of the dehydrogenase unit (Wanders et al., 2001). This classification can be made on the basis of enzyme activity measurements in combination with mutation analysis, as described by Gloerich et al. (2003). </p>
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<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
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</h4>
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<span class="mim-text-font">
<p>The diagnosis of DBP deficiency is commonly made based on the accumulation of very long chain fatty acids (VLCFA), dihydroxy- and trihydroxycholestanoic acid (DHCA and THCA), and pristanic and phytanic acid in plasma. However, some patients with residual enzyme activity may not have abnormal plasma values, making the diagnosis difficult. Gronborg et al. (2010) reported 2 sibs with the disorder who were initially found to have normal VLCFA plasma values when studied based on clinical features. Features included neonatal hypotonia, early-onset seizures, and severe developmental delay. Both also had hearing loss and showed developmental regression at about age 4 years. The older sib died at age 10 years, 9 months, without correct diagnosis. Brain MRI in the 2 sibs at ages 28 and 30 months, respectively, showed typical findings of a peroxisomal disorder, prompting repeated plasma examination in the younger sib and studies of patient fibroblasts, which led to proper molecular diagnosis. The MRI findings included leukoencephalopathy of cerebral and cerebellar white matter, polymicrogyria, and pachygyria. Gronborg et al. (2010) concluded that brain MRI may aid in the diagnosis of patients with DBP deficiency, particularly in cases with no or mild plasma abnormalities. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Suzuki et al. (1999) reported the first successful prenatal diagnosis of D-bifunctional protein deficiency using cultured amniocytes obtained from a fetus at 16 weeks' gestation. These authors used several methods, including an assay for lignoceric acid oxidation activity, indirect immunofluorescence staining and immunoblot analysis for the presence of DBP, and genetic analysis using RT-PCR. After pregnancy termination, immunohistochemical and biochemical studies of the fetus confirmed their prenatal diagnosis. </p>
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<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
<p>In 2 Japanese patients reported by Suzuki et al. (1994) as having L-bifunctional protein deficiency, Suzuki et al. (1997) identified 2 different homozygous deletions in the HSD17B4 gene (601860.0001; 601860.0002), confirming D-bifunctional protein deficiency. </p><p>In 9 patients who carried the diagnosis of L-bifunctional protein deficiency on the basis of complementation analysis, van Grunsven et al. (1999) identified mutations in the HSD17B4 gene, confirming a diagnosis of D-bifunctional protein deficiency. Four of the 9 patients had the same mutation (601860.0003). </p><p>In a patient with D-bifunctional protein deficiency originally reported by Watkins et al. (1989), van Grunsven et al. (1999) identified a homozygous 2-bp deletion in the HSD17B4 gene (601860.0007). The patient was originally thought to have L-bifunctional protein deficiency based on immunoblot analysis of postmortem liver tissue. However, reanalysis showed accumulation of both very long chain fatty acids and bile acid intermediates, which was hard to reconcile with an isolated deficiency of the L-bifunctional protein. The results suggested that most, if not all, patients whose peroxisomal disorder had been diagnosed as L-bifunctional protein deficiency were in fact cases of D-bifunctional protein deficiency. </p><p>Ferdinandusse et al. (2006) reported the mutational spectrum of DBP deficiency on the basis of molecular analysis in 110 patients. They identified 61 different mutations by DBP cDNA analysis, 48 of which had not been previously reported. The predicted effects of the different disease-causing amino acid changes in protein structure were determined using the crystal structures. The effects ranged from the replacement of catalytic amino acid residues or residues in direct contact with the substrate or cofactor to disturbances of protein folding or dimerization of the subunits. To study whether there is a genotype-phenotype correlation for DBP deficiency, these structure-based analyses were combined with extensive biochemical analyses of patient material (cultured skin fibroblasts and plasma) and available clinical information on the patients. They found that the effect of the mutations identified in patients with a relatively mild clinical and biochemical presentation was less detrimental to the protein structure than the effect of mutations identified in those with a very severe presentation. These results suggested that the amount of residual DBP activity correlates with the severity of the phenotype. Thus the data indicated that on the basis of the predicted effect of mutations on protein structure, a genotype-phenotype correlation exists for DBP deficiency. </p>
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<h4>
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<strong>Population Genetics</strong>
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<p>DBP deficiency has an estimated prevalence of 1 in 100,000 (Ferdinandusse et al., 2006). </p>
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<h4>
<span class="mim-font">
<strong>See Also:</strong>
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</h4>
<span class="mim-text-font">
Naidu et al. (1988)
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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<ol>
<li>
<p class="mim-text-font">
Clayton, P. T., Patel, E., Lawson, A. M., Carruthers, R. A., Collins, J.
<strong>Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.</strong>
J. Clin. Invest. 85: 1267-1273, 1990.
[PubMed: 2318981]
[Full Text: https://doi.org/10.1172/JCI114563]
</p>
</li>
<li>
<p class="mim-text-font">
Ferdinandusse, S., Denis, S., Mooyer, P. A. W., Dekker, C., Duran, M., Soorani-Lunsing, R. J., Boltshauser, E., Macaya, A., Gartner, J., Majoie, C. B. L. M., Barth, P. G., Wanders, R. J. A., Poll-The, B. T.
<strong>Clinical and biochemical spectrum of D-bifunctional protein deficiency.</strong>
Ann. Neurol. 59: 92-104, 2006.
[PubMed: 16278854]
[Full Text: https://doi.org/10.1002/ana.20702]
</p>
</li>
<li>
<p class="mim-text-font">
Ferdinandusse, S., van Grunsven, E. G., Oostheim, W., Denis, S., Hogenhout, E. M., Ijlst, L., van Roermund, C. W. T., Waterham, H. R., Goldfischer, S., Wanders, R. J. A.
<strong>Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of D-bifunctional protein.</strong>
Am. J. Hum. Genet. 70: 1589-1593, 2002.
[PubMed: 11992265]
[Full Text: https://doi.org/10.1086/340970]
</p>
</li>
<li>
<p class="mim-text-font">
Ferdinandusse, S., Ylianttila, M. S., Gloerich, J., Koski, M. K., Oostheim, W., Waterham, H. R., Hiltunen, J. K., Wanders, R. J. A., Glumoff, T.
<strong>Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.</strong>
Am. J. Hum. Genet. 78: 112-124, 2006.
[PubMed: 16385454]
[Full Text: https://doi.org/10.1086/498880]
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<li>
<p class="mim-text-font">
Gloerich, J., Denis, S., Van Grunsven, E. G., Dacremont, G., Wanders, R. J., Ferdinandusse, S.
<strong>A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency.</strong>
J. Lipid Res. 44: 640-644, 2003.
[PubMed: 12562856]
[Full Text: https://doi.org/10.1194/jlr.D200039-JLR200]
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</li>
<li>
<p class="mim-text-font">
Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J., Van Hoof, F.
<strong>Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.</strong>
J. Pediat. 108: 25-32, 1986.
[PubMed: 2868085]
[Full Text: https://doi.org/10.1016/s0022-3476(86)80764-8]
</p>
</li>
<li>
<p class="mim-text-font">
Gronborg, S., Kratzner, R., Spiegler, J., Ferdinandusse, S., Wanders, R. J. A., Waterham, H. R., Gartner, J.
<strong>Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.</strong>
Am. J. Med. Genet. 152A: 2845-2849, 2010.
[PubMed: 20949532]
[Full Text: https://doi.org/10.1002/ajmg.a.33677]
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</li>
<li>
<p class="mim-text-font">
McMillan, H. J., Worthylake, T., Schwartzentruber, J., Gottlieb, C. C., Lawrence, S. E., MacKenzie, A., Beaulieu, C. L., Mooyer, P. A. W., FORGE Canada Consortium, Wanders, R. J. A., Majewski, J., Bulman, D. E., Geraghty, M. T., Ferdinandusse, S., Boycott, K. M.
<strong>Specific combination of compound heterozygous mutations in 17-beta-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency.</strong>
Orphanet J. Rare Dis. 7: 90, 2012. Note: Electronic Article.
[PubMed: 23181892]
[Full Text: https://doi.org/10.1186/1750-1172-7-90]
</p>
</li>
<li>
<p class="mim-text-font">
Naidu, S., Hoefler, G., Watkins, P. A., Chen, W. W., Moser, A. B., Hoefler, S., Rance, N. E., Powers, J. M., Beard, M., Green, W. R., Hashimoto, T., Moser, H. W.
<strong>Neonatal seizures and retardation in a female with biochemical features of X-linked adrenoleukodystrophy: a possible new peroxisomal disease entity.</strong>
Neurology 38: 1100-1107, 1988.
[PubMed: 3386829]
[Full Text: https://doi.org/10.1212/wnl.38.7.1100]
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<li>
<p class="mim-text-font">
Nakada, Y., Hyakuna, N., Suzuki, Y., Shimozawa, N., Takaesu, E., Ikema, R., Hirayama, K.
<strong>A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein: comparison of two cases of Zellweger syndrome.</strong>
Brain Dev. 15: 453-456, 1993.
[PubMed: 8147505]
[Full Text: https://doi.org/10.1016/0387-7604(93)90087-o]
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<li>
<p class="mim-text-font">
Nakano, K., Zhang, Z., Shimozawa, N., Kondo, N., Ishii, N., Funatsuka, M., Shirakawa, S., Itoh, M., Takashima, S., Une, M., Kana-aki, R. R., Mukai, K., Osawa, M., Suzuki, Y.
<strong>D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes.</strong>
J. Pediat. 139: 865-867, 2001.
[PubMed: 11743515]
[Full Text: https://doi.org/10.1067/mpd.2001.119170]
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<li>
<p class="mim-text-font">
Pierce, S. B., Walsh, T., Chisholm, K. M., Lee, M, K., Thornton, A. M., Fiumara, A., Opitz, J. M., Levy-Lahad, E., Klevit, R. E., King, M.-C.
<strong>Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome.</strong>
Am. J. Hum. Genet. 87: 282-288, 2010.
[PubMed: 20673864]
[Full Text: https://doi.org/10.1016/j.ajhg.2010.07.007]
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</li>
<li>
<p class="mim-text-font">
Schram, A. W., Goldfischer, S., van Roermund, C. W. T., Brouwer-Kelder, E. M., Collins, J., Hashimoto, T., Heymans, H. S. A., van den Bosch, H., Schutgens, R. B. H., Tager, J. M., Wanders, R. J. A.
<strong>Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.</strong>
Proc. Nat. Acad. Sci. 84: 2494-2496, 1987.
[PubMed: 2882519]
[Full Text: https://doi.org/10.1073/pnas.84.8.2494]
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<li>
<p class="mim-text-font">
Suzuki, Y., Jiang, L. L., Souri, M., Miyazawa, S., Fukuda, S., Zhang, Z., Une, M., Shimozawa, N., Kondo, N., Orii, T., Hashimoto, T.
<strong>D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.</strong>
Am. J. Hum. Genet. 61: 1153-1162, 1997.
[PubMed: 9345094]
[Full Text: https://doi.org/10.1086/301599]
</p>
</li>
<li>
<p class="mim-text-font">
Suzuki, Y., Shimozawa, N., Yajima, S., Tomatsu, S., Kondo, N., Nakada, Y., Akaboshi, S., Iai, M., Tanabe, Y., Hashimoto, T., Wanders, R. J. A., Schutgens, R. B. H., Moser, H. W., Orii, T.
<strong>Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis.</strong>
Am. J. Hum. Genet. 54: 36-43, 1994.
[PubMed: 8279468]
</p>
</li>
<li>
<p class="mim-text-font">
Suzuki, Y., Zhang, Z., Shimozawa, N., Muro, M., Shono, H., Toda, S., Miyahara, S., Hashimoto, T., Usuda, N., Ito, M., Takashima, S., Kondo, N.
<strong>Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency.</strong>
J. Hum. Genet. 44: 143-147, 1999.
[PubMed: 10319576]
[Full Text: https://doi.org/10.1007/s100380050131]
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<li>
<p class="mim-text-font">
van Grunsven, E. G., van Berkel, E., Ijlst, L., Vreken, P., de Klerk, J. B. C., Adamski, J., Lemonde, H., Clayton, P. T., Cuebas, D. A., Wanders, R. J. A.
<strong>Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency.</strong>
Proc. Nat. Acad. Sci. 95: 2128-2133, 1998.
[PubMed: 9482850]
[Full Text: https://doi.org/10.1073/pnas.95.5.2128]
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</li>
<li>
<p class="mim-text-font">
van Grunsven, E. G., van Berkel, E., Mooijer, P. A. W., Watkins, P. A., Moser, H. W., Suzuki, Y., Jiang, L. L., Hashimoto, T., Hoefler, G., Adamski, J., Wanders, R. J. A.
<strong>Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis.</strong>
Am. J. Hum. Genet. 64: 99-107, 1999.
[PubMed: 9915948]
[Full Text: https://doi.org/10.1086/302180]
</p>
</li>
<li>
<p class="mim-text-font">
Wanders, R. J. A., Barth, P. G., Heymans, H. S. A.
<strong>Single peroxisomal enzyme deficiencies.In: Scriver C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Molecular and Metabolic Bases of Inherited Disease.</strong>
McGraw-Hill, New York 2001. Pp. 3219-3256.
</p>
</li>
<li>
<p class="mim-text-font">
Wanders, R. J. A., van Roermund, C. W. T., Brus, S., Schutgens, R. B. H., Tager, J. M., Jakobs, C.
<strong>Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis.</strong>
J. Inherit. Metab. Dis. 15: 385-388, 1992.
[PubMed: 1357231]
[Full Text: https://doi.org/10.1007/BF02435983]
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<li>
<p class="mim-text-font">
Wanders, R. J. A., van Roermund, C. W. T., Schelen, A., Schutgens, R. B. H., Tager, J. M., Stephenson, J. B. P., Clayton, P. T.
<strong>A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities.</strong>
J. Inherit. Metab. Dis. 13: 375-379, 1990.
[PubMed: 2122104]
[Full Text: https://doi.org/10.1007/BF01799399]
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<li>
<p class="mim-text-font">
Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., Jr., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E., Moser, H. W.
<strong>Peroxisomal bifunctional enzyme deficiency.</strong>
J. Clin. Invest. 83: 771-777, 1989.
[PubMed: 2921319]
[Full Text: https://doi.org/10.1172/JCI113956]
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Watkins, P. A., McGuinness, M. C., Raymond, G. V., Hicks, B. A., Sisk, J. M., Moser, A. B., Moser, H. W.
<strong>Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies.</strong>
Ann. Neurol. 38: 472-477, 1995.
[PubMed: 7668838]
[Full Text: https://doi.org/10.1002/ana.410380322]
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