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- #266500 - REFSUM DISEASE, CLASSIC
- OMIM
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<span class="h4">#266500</span>
<br />
<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/266500"><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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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#nomenclature">Nomenclature</a>
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<a href="#history">History</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=REFSUM DISEASE, CLASSIC" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." 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=381&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.ncbi.nlm.nih.gov/books/NBK1353/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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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:10582" 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/266500" 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:10582" 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 panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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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>
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<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:266500" 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>
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<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.">
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<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> 25362006<br />
<strong>ICD10CM:</strong> G60.1<br />
<strong>ICD9CM:</strong> 356.3<br />
<strong>ORPHA:</strong> 773<br />
<strong>DO:</strong> 10582<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>
266500
</span>
</span>
</div>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
REFSUM DISEASE, CLASSIC
</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">
REFSUM DISEASE, ADULT, 1<br />
PHYTANIC ACID OXIDASE DEFICIENCY<br />
HEREDOPATHIA ATACTICA POLYNEURITIFORMIS<br />
HEREDITARY MOTOR AND SENSORY NEUROPATHY IV; HMSN4<br />
HMSN IV
</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/10/63?start=-3&limit=10&highlight=63">
10p13
</a>
</span>
</td>
<td>
<span class="mim-font">
Refsum disease
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/266500"> 266500 </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">
PHYH
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602026"> 602026 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
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<a href="/clinicalSynopsis/266500" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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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/266500" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/266500" 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> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sensorineural deafness, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749351&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749351</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</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">
- Retinitis pigmentosa <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28835009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28835009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H35.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H35.52</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035334&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035334</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000510</a>]</span><br /> -
Retinal degeneration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95695004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95695004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035304&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035304</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span><br /> -
Night blindness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65194006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65194006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.6</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.60</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.6</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/368.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000662</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000662</a>]</span><br /> -
Constriction of visual fields <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1151008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1151008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235095&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235095</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001133" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001133</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 /> -
Miosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415219007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415219007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63251006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63251006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301939004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H57.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H57.03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026205&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026205</a>, <a href="https://bioportal.bioontology.org/search?q=C0728710&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728710</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000616</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000616</a>]</span><br /> -
Poor pupillary reaction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5562982&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5562982</a>]</span><br /> -
Cataracts <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</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">
- Anosmia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44169009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44169009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R43.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R43.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003126&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003126</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000458" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000458</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000458" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000458</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85898001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85898001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57809008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57809008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0878544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0878544</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span><br /> -
Cardiomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8186001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8186001</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">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/429.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">429.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018800&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018800</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</a>]</span><br /> -
Cardiac failure (sudden death has been reported) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84114007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84114007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42343007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42343007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I50</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/428.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/428" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/428.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018802</a>, <a href="https://bioportal.bioontology.org/search?q=C0018801&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018801</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span><br /> -
Electrocardiographic abnormalities <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/102594003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">102594003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0522055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0522055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003115" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003115</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 dysfunction (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/723188008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">723188008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/236423003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">236423003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279454</a>, <a href="https://bioportal.bioontology.org/search?q=C1565489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1565489</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</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">
- Multiple epiphyseal dysplasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59708000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59708000</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/756.56" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">756.56</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1456376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1456376</a>, <a href="https://bioportal.bioontology.org/search?q=C0026760&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026760</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002654</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002654</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">
- Shortening of the metacarpals <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837084&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837084</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010049" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010049</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">
- Shortening of the metatarsals <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849020&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849020</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010743" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010743</a>]</span><br /> -
Pes cavus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205091006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205091006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36755004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36755004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86900005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86900005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.73</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/754.71" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.71</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0728829&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728829</a>, <a href="https://bioportal.bioontology.org/search?q=C0039273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039273</a>, <a href="https://bioportal.bioontology.org/search?q=C2239098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Pes_Cavus-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610&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 />
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<strong> SKIN, NAILS, & HAIR </strong>
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<em> Skin </em>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Ichthyosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/782957005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">782957005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13059002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13059002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q80.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q80.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q80" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q80</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/757.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">757.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020758</a>, <a href="https://bioportal.bioontology.org/search?q=C0020757&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020757</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008064" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008064</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008064" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008064</a>]</span><br />
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<strong> NEUROLOGIC </strong>
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<em> Central Nervous System </em>
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- Increased CSF protein with normal cell count <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749347&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749347</a>]</span><br />
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- Peripheral sensorimotor neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1112256&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1112256</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007141</a>]</span><br /> -
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Limb atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749348&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749348</a>]</span><br /> -
Limb weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/713514005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">713514005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0587246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0587246</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003690" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003690</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003690" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003690</a>]</span><br /> -
Sensory impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398026008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398026008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5551413&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5551413</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003474</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003474</a>]</span><br /> -
Nerve hypertrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749349&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749349</a>]</span><br />
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<strong> LABORATORY ABNORMALITIES </strong>
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<span class="mim-font">
- Increased phytanic acid in body tissues and fluids <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749353</a>]</span><br /> -
Decreased phytanic acid oxidase activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749354</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Affected infants appear normal<br /> -
Symptoms show insidious onset in the late first through third decades<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the phytanoyl-CoA hydroxylase gene (PHYH, <a href="/entry/602026#0001">602026.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that classic Refsum disease is caused by homozygous or compound hterozygous mutation in the gene encoding phytanoyl-CoA hydroxylase (PHYH, or PAHX; <a href="/entry/602026">602026</a>) on chromosome 10p13.</p>
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<strong>Description</strong>
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<p>Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia (review by <a href="#29" class="mim-tip-reference" title="Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H. &lt;strong&gt;Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.&lt;/strong&gt; J. Neurol. Sci. 77: 87-96, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2433405/&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;2433405&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(87)90209-7&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="2433405">Skjeldal et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2433405" 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>Increased levels of phytanic acid can also be found in peroxisomal biogenesis disorders; see Zellweger syndrome (see <a href="/entry/214100">214100</a>) (<a href="#29" class="mim-tip-reference" title="Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H. &lt;strong&gt;Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.&lt;/strong&gt; J. Neurol. Sci. 77: 87-96, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2433405/&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;2433405&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(87)90209-7&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="2433405">Skjeldal et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2433405" 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>Infantile Refsum disease (see PBD1B, <a href="/entry/601539">601539</a>) is a distinct disorder with a different phenotype and genetic basis.</p><p>A phenotype clinically indistinguishable from that of classic Refsum disease (PBD9B; <a href="/entry/614879">614879</a>), but with a different biochemical profile, can be caused by mutation in the gene encoding peroxin-7 (PEX7; <a href="/entry/601757">601757</a>) on chromosome 6q.</p>
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<strong>Clinical Features</strong>
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<p><a href="#24" class="mim-tip-reference" title="Refsum, S. &lt;strong&gt;Heredopathica atactica polyneuritiformis: a familial syndrome not hitherto described.&lt;/strong&gt; Acta Psychiat. Scand. Suppl. 38: :1-303, 1946."None>Refsum (1946)</a> first described this disorder and noted the hereditary aspect.</p><p><a href="#29" class="mim-tip-reference" title="Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H. &lt;strong&gt;Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.&lt;/strong&gt; J. Neurol. Sci. 77: 87-96, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2433405/&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;2433405&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(87)90209-7&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="2433405">Skjeldal et al. (1987)</a> reported the clinical features of 17 patients with Refsum disease. Although onset of symptoms was reportedly insidious, they generally were reported to occur late in the first decade through the third decade of life. All patients had retinitis pigmentosa with night blindness and constriction of the visual fields, and many patients had cataracts. All had some sign of polyneuropathy, most commonly impaired reflexes, and most patients also had sensory disturbances and limb paresis or atrophy. Only 5 patients had clear cerebellar ataxia. Other common features included anosmia and progressive hearing loss. Skin changes, cardiac abnormalities, and skeletal manifestations were less common. Serum phytanic acid was increased in those who had not been treated by diet, and phytanic acid oxidase activity in fibroblasts was very low. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2433405" 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="#16" class="mim-tip-reference" title="Leys, D., Petit, H., Bonte-Adnet, C., Millaire, A., Fourrier, F., Dubois, F., Rousseaux, M., Ducloux, G. &lt;strong&gt;Refsum&#x27;s disease revealed by cardiac disorders. (Letter)&lt;/strong&gt; Lancet 333: 621 only, 1989. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2466186/&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;2466186&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(89)91654-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2466186">Leys et al. (1989)</a> described 2 brothers who presented in their twenties with severe heart failure as the predominant clinical manifestation of Refsum disease. Both of them had retinitis pigmentosa with lack of ERG response, miosis, anosmia, and bilateral shortening of the fourth metatarsals, but no cataracts or deafness. One of them had mild bilateral ptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2466186" 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="inheritance" class="mim-anchor"></a>
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<p>The transmission pattern of classic Refsum disease in the family of patients 1 and 2 reported by <a href="#11" class="mim-tip-reference" title="Jansen, G. A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., Besley, G. T. N., Wraith, J. E., Wanders, R. J. A. &lt;strong&gt;Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.&lt;/strong&gt; Nature Genet. 17: 190-193, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326940/&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;9326940&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1097-190&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="9326940">Jansen et al. (1997)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326940" 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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<strong>Biochemical Features</strong>
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<p><a href="#15" class="mim-tip-reference" title="Klenk, E., Kahlke, W. &lt;strong&gt;Ueber das Vorkommen der 3.7.11.15-tetramethyl-hexadecansaeure (Phytansaeure) in den Cholesterinestern und anderen Lipoidfraktionen der Organe bei einem Krankheitsfall unbekannter Genese (Verdacht auf heredopathia atactica polyneuritiformis Refsum-syndrom).&lt;/strong&gt; Hoppe Seylers Z. Physiol. Chem. 333: 133-142, 1963.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14058273/&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;14058273&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1515/bchm2.1963.333.1.133&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="14058273">Klenk and Kahlke (1963)</a> discovered that patients with hereditary ataxia and polyneuritis of the Refsum type have accumulation of the phytanic acid, an unusual branched-chain fatty acid (3,7,11,15-tetramethyl-hexadecanoic acid), in tissues and body fluids. Further studies showed that the defect in Refsum disease involves lack of proper degradation of phytanic acid, which is exclusively derived from exogenous sources. Exogenous phytol is readily converted to phytanic acid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14058273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Steinberg, D., Herndon, J. H., Jr., Uhlendorf, B. W., Mize, C. E., Avigan, J., Milne, G. W. A. &lt;strong&gt;Refsum&#x27;s disease: nature of the enzyme defect.&lt;/strong&gt; Science 156: 1740-1742, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4180573/&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;4180573&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.156.3783.1740&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="4180573">Steinberg et al. (1967)</a> found that cultured fibroblasts from patients with Refsum disease showed very low oxidation of C14-labeled phytanic acid, but normal oxidation of pristanic acid, which is known to be the first product of phytanic acid degradation. The authors concluded that the defect resides in the enzyme that catalyzes the alpha-oxidative process by which phytanic acid is shortened by one carbon atom. Studies of cultured fibroblasts from patients with Refsum disease also led <a href="#9" class="mim-tip-reference" title="Herndon, J. H., Jr., Steinberg, D., Uhlendorf, B. W. &lt;strong&gt;Refsum&#x27;s disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes.&lt;/strong&gt; New Eng. J. Med. 281: 1034-1038, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4188238/&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;4188238&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196911062811903&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="4188238">Herndon et al. (1969)</a> to the conclusion that the enzyme involved in alpha-hydroxylation of phytanate is deficient, whereas enzymes involved in later steps are normal. <a href="#34" class="mim-tip-reference" title="Steinberg, D. &lt;strong&gt;Personal Communication.&lt;/strong&gt; La Jolla, Calif. 2/1982."None>Steinberg (1982)</a> suggested that the enzyme deficient in this disorder may be a mixed-function oxygenase. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4180573+4188238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Jansen, G. A., Wanders, R. J. A., Watkins, P. A., Mihalik, S. J. &lt;strong&gt;Phytanoyl-coenzyme A hydroxylase deficiency--the enzyme defect in Refsum&#x27;s disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 337: 133-134, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9221344/&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;9221344&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199707103370215&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="9221344">Jansen et al. (1997)</a> noted that phytanic acid normally undergoes alpha-oxidation in which the chain is shortened by 1 carbon atom, yielding pristanic acid and carbon dioxide. Pristanic acid can be degraded by beta-oxidation to yield 3 molecules of acetyl-coenzyme A (CoA), 3 of propionyl-CoA, and 1 of isobutyryl-CoA. Patients with Refsum disease have deficient alpha-oxidation of (14)C-phytanic acid to pristanic acid, whereas the subsequent beta-oxidation of pristanic acid is normal. <a href="#12" class="mim-tip-reference" title="Jansen, G. A., Wanders, R. J. A., Watkins, P. A., Mihalik, S. J. &lt;strong&gt;Phytanoyl-coenzyme A hydroxylase deficiency--the enzyme defect in Refsum&#x27;s disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 337: 133-134, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9221344/&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;9221344&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199707103370215&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="9221344">Jansen et al. (1997)</a> reported that phytanoyl-CoA hydroxylase activity was undetectable in liver tissue from a patient with Refsum disease. On the basis of these findings, they stated that Refsum disease can be classified as a true peroxisomal disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9221344" 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="Mihalik, S. J., Morrell, J. C., Kim. D., Sacksteder, K. A., Watkins, P. A., Gould, S. J. &lt;strong&gt;Identification of PAHX, a Refsum disease gene.&lt;/strong&gt; Nature Genet. 17: 185-189, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326939/&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;9326939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1097-185&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="9326939">Mihalik et al. (1997)</a> observed that decreased phytanic-acid oxidation is also observed in human cells lacking PEX7 (<a href="/entry/601757">601757</a>), the receptor for the type 2 peroxisomal targeting signal (PTS2), suggesting that the enzyme defective in Refsum disease is targeted to peroxisomes by a PTS2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326939" 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="#35" class="mim-tip-reference" title="Tranchant, C., Aubourg, P., Mohr, M., Rocchiccioli, F., Zaenker, C., Warter, J. M. &lt;strong&gt;A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.&lt;/strong&gt; Neurology 43: 2044-2048, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8413964/&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;8413964&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.43.10.2044&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="8413964">Tranchant et al. (1993)</a> described 4 patients with adult Refsum disease having, in addition to the usual biochemical features, accumulation of L-pipecolic acid, another metabolite (derived from L-lysine) catabolized in peroxisomes. The youngest brother died at age 17 from a rapidly progressing neurologic deterioration, suggesting that the patients may suffer from a peroxisomal disorder intermediate between infantile Refsum disease and adult Refsum disease. <a href="#20" class="mim-tip-reference" title="Nadal, N., Rolland, M.-O., Tranchant, C., Reutenauer, L., Gyapay, G., Warter, J.-M., Mandel, J.-L., Koenig, M. &lt;strong&gt;Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family.&lt;/strong&gt; Hum. Molec. Genet. 4: 1963-1966, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8595422/&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;8595422&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/4.10.1963&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="8595422">Nadal et al. (1995)</a> referred to this disorder as Refsum disease with increased pipecolic acidemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8595422+8413964" 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="#6" class="mim-tip-reference" title="Eldjarn, L., Try, K., Stokke, O., Munthe-Kaas, A. W., Refsum, S., Steinberg, D., Avigan, J., Mize, C. E. &lt;strong&gt;Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis.&lt;/strong&gt; Lancet 287: 691-693, 1966. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4159604/&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;4159604&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(66)91632-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4159604">Eldjarn et al. (1966)</a> showed that with a diet free of chlorophyll and of foods which might contain phytol, phytanic acid, or their precursors, phytanic acid could be reduced in the blood and clinical improvement effected. Plasmapheresis performed once or twice a month effectively removes phytanic acid from the body and permits liberalization of dietary restriction while preventing progression of the clinical features (<a href="#7" class="mim-tip-reference" title="Gibberd, F. B., Page, N. G. R., Billimoria, J. D., Retsas, S. &lt;strong&gt;Heredopathia atactica polyneuritiformis (Refsum&#x27;s disease) treated by diet and plasma-exchange.&lt;/strong&gt; Lancet 313: 575-578, 1979. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/85164/&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;85164&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(79)91005-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="85164">Gibberd et al., 1979</a>; <a href="#19" class="mim-tip-reference" title="Moser, H. W., Braine, H., Pyeritz, R. E., Ullman, D. D., Murray, C., Asbury, A. K. &lt;strong&gt;Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease.&lt;/strong&gt; Birth Defects Orig. Art. Ser. 16(1): 491-497, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6160883/&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;6160883&lt;/a&gt;]" pmid="6160883">Moser et al., 1980</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4159604+85164+6160883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Robertson, E. F., Poulos, A., Sharp, P., Manson, J., Wise, G., Jaunzems, A., Carter, R. &lt;strong&gt;Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.&lt;/strong&gt; Europ. J. Pediat. 147: 133-142, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2452736/&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;2452736&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00442210&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="2452736">Robertson et al. (1988)</a> treated 2 patients with low phytanic acid diet and reported a decrease in plasma phytanic acid levels, a marked decrease in plasma pipecolic acid, and a relatively slow decrease in the C26-C22 fatty acid ratios, which remained markedly abnormal even after 2 years. Clinical data suggested stabilization or perhaps slight improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2452736" 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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<div>
<a id="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Mapping</strong>
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<p><a href="#20" class="mim-tip-reference" title="Nadal, N., Rolland, M.-O., Tranchant, C., Reutenauer, L., Gyapay, G., Warter, J.-M., Mandel, J.-L., Koenig, M. &lt;strong&gt;Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family.&lt;/strong&gt; Hum. Molec. Genet. 4: 1963-1966, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8595422/&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;8595422&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/4.10.1963&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="8595422">Nadal et al. (1995)</a> localized the Refsum disease gene to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family. The PHYH gene maps to this region (<a href="#17" class="mim-tip-reference" title="Mihalik, S. J., Morrell, J. C., Kim. D., Sacksteder, K. A., Watkins, P. A., Gould, S. J. &lt;strong&gt;Identification of PAHX, a Refsum disease gene.&lt;/strong&gt; Nature Genet. 17: 185-189, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326939/&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;9326939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1097-185&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="9326939">Mihalik et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8595422+9326939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Nadal, N., Rolland, M.-O., Tranchant, C., Reutenauer, L., Gyapay, G., Warter, J.-M., Mandel, J.-L., Koenig, M. &lt;strong&gt;Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family.&lt;/strong&gt; Hum. Molec. Genet. 4: 1963-1966, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8595422/&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;8595422&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/4.10.1963&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="8595422">Nadal et al. (1995)</a> performed genomewide linkage analysis in the family described by <a href="#35" class="mim-tip-reference" title="Tranchant, C., Aubourg, P., Mohr, M., Rocchiccioli, F., Zaenker, C., Warter, J. M. &lt;strong&gt;A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.&lt;/strong&gt; Neurology 43: 2044-2048, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8413964/&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;8413964&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.43.10.2044&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="8413964">Tranchant et al. (1993)</a> with increased pipecolic acidemia and demonstrated linkage with significant lod score values by the combination of 3 independent sources of information: multiple affected sibs, first-degree consanguinity, and biochemical discrimination between healthy heterozygous carriers and noncarriers. The study illustrated the power of a dense map of microsatellite markers combined with classic linkage analysis and homozygosity mapping. They obtained a lod score of 3.6 between the phenotype and the interval defined by D10S249 and D10S466 on 10p in this single consanguineous family. Since this disorder maps to the same site at the tip of the short arm of chromosome 10 where the gene for phytanoyl-CoA hydroxylase (PHYH) also maps, and since the PHYH gene is the site of mutations in classic Refsum disease, mutations in that gene should be sought in these cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8595422+8413964" 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><a href="#17" class="mim-tip-reference" title="Mihalik, S. J., Morrell, J. C., Kim. D., Sacksteder, K. A., Watkins, P. A., Gould, S. J. &lt;strong&gt;Identification of PAHX, a Refsum disease gene.&lt;/strong&gt; Nature Genet. 17: 185-189, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326939/&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;9326939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1097-185&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="9326939">Mihalik et al. (1997)</a> found that both Refsum disease patients examined were homozygous for inactivating mutations in the PHYH gene (<a href="/entry/602026#0001">602026.0001</a> and <a href="/entry/602026#0002">602026.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326939" 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>Independently, <a href="#11" class="mim-tip-reference" title="Jansen, G. A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., Besley, G. T. N., Wraith, J. E., Wanders, R. J. A. &lt;strong&gt;Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.&lt;/strong&gt; Nature Genet. 17: 190-193, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326940/&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;9326940&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1097-190&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="9326940">Jansen et al. (1997)</a> identified mutations in the PHYH gene in 5 patients with Refsum disease, including a 1-bp deletion, a 111-bp deletion, and a point mutation (<a href="/entry/602026#0002">602026.0002</a>-<a href="/entry/602026#0004">602026.0004</a>). Some of the patients had been reported by <a href="#29" class="mim-tip-reference" title="Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H. &lt;strong&gt;Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.&lt;/strong&gt; J. Neurol. Sci. 77: 87-96, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2433405/&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;2433405&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(87)90209-7&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="2433405">Skjeldal et al. (1987)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9326940+2433405" 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 22 patients with Refsum disease, <a href="#10" class="mim-tip-reference" title="Jansen, G. A., Hogenhout, E. M., Ferdinandusse, S., Waterham, H. R., Ofman, R., Jakobs, C., Skjeldal, O. H., Wanders, R. J. A. &lt;strong&gt;Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum&#x27;s disease.&lt;/strong&gt; Hum. Molec. Genet. 9: 1195-1200, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10767344/&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;10767344&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/9.8.1195&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="10767344">Jansen et al. (2000)</a> identified mutations in the PHYH gene, including 14 different missense mutations, a 3-bp insertion, and a 1-bp deletion, which were all confirmed at the genome level (see, e.g., <a href="/entry/602026#0005">602026.0005</a>-<a href="/entry/602026#0009">602026.0009</a>). A 111-bp deletion (<a href="/entry/602026#0002">602026.0002</a>) identified in the PHYH cDNA of several patients with Refsum disease was due to either 1 of 2 different mutations in the same splice acceptor site, which result in skipping of exon 3. Six mutations were expressed in S. cerevisiae, and all led to an enzymatically inactive PhyH protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767344" 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="nomenclature" class="mim-anchor"></a>
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<strong>Nomenclature</strong>
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<p>The designation 'infantile Refsum disease' (see <a href="/entry/601539">601539</a>), or infantile phytanic acid storage disease, was used for a congenital disorder with some clinical features resembling Refsum disease and with phytanic acid accumulation. However, since it subsequently proved to be a peroxisome biogenesis disorder, <a href="#13" class="mim-tip-reference" title="Jansen, G. A., Waterham, H. R., Wanders, R. J. A. &lt;strong&gt;Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).&lt;/strong&gt; Hum. Mutat. 23: 209-218, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14974078/&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;14974078&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.10315&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="14974078">Jansen et al. (2004)</a> suggested that the designation is unfortunate and should be discarded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14974078" 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="history" class="mim-anchor"></a>
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<strong>History</strong>
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<p><a href="#21" class="mim-tip-reference" title="Nyberg-Hansen, R. &lt;strong&gt;Obituary: Sigvald Refsum (1907-1991).&lt;/strong&gt; J. Neurol. Sci. 107: 125-126, 1992."None>Nyberg-Hansen (1992)</a> provided an obituary of Sigvald Refsum, 1907-1991.</p>
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<a id="seeAlso" class="mim-anchor"></a>
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<strong>See Also:</strong>
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</h4>
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<span class="mim-text-font">
<a href="#Ashenhurst1958" class="mim-tip-reference" title="Ashenhurst, E. M., Millar, J. H. D., Milliken, T. G. &lt;strong&gt;Refsum&#x27;s syndrome affecting a brother and two sisters.&lt;/strong&gt; Brit. Med. J. 2: 415-417, 1958.">Ashenhurst et al. (1958)</a>; <a href="#Billimoria1982" class="mim-tip-reference" title="Billimoria, J. D., Clemens, M. E., Gibberd, F. B., Whitelaw, M. N. &lt;strong&gt;Metabolism of phytanic acid in Refsum&#x27;s disease.&lt;/strong&gt; Lancet 319: 194-196, 1982. Note: Originally Volume I.">Billimoria et al. (1982)</a>; <a href="#Braverman2002" class="mim-tip-reference" title="Braverman, N., Chen, L., Lin, P., Obie, C., Steel, G., Douglas, P., Chakraborty, P. K., Clarke, J. T. R., Boneh, A., Moser, A., Moser, H., Valle, D. &lt;strong&gt;Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype.&lt;/strong&gt; Hum. Mutat. 20: 284-297, 2002.">Braverman et al.
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et al. (1969)</a>; <a href="#Kahlke1966" class="mim-tip-reference" title="Kahlke, W., Wagener, H. &lt;strong&gt;Conversion of h3-phytol to phytanic acid and its incorporation into plasma lipid fractions in heredopathia atactica polyneuritiformis.&lt;/strong&gt; Metabolism 15: 687-693, 1966.">Kahlke and Wagener (1966)</a>; <a href="#Mize1969" class="mim-tip-reference" title="Mize, C. E., Herndon, J. H., Jr., Blass, J. P., Milne, G. W. A., Follansbee, C., Laudat, P., Steinberg, D. &lt;strong&gt;Localization of the oxidative defect in phytanic acid degradation in patients with Refsum&#x27;s disease.&lt;/strong&gt; J. Clin. Invest. 48: 1033-1040, 1969.">Mize et al. (1969)</a>; <a href="#Poulos1984" class="mim-tip-reference" title="Poulos, A., Pollard, A. C., Mitchell, J. D., Wise, G., Mortimer, G. &lt;strong&gt;Patterns of Refsum&#x27;s disease: phytanic acid oxidase deficiency.&lt;/strong&gt; Arch. Dis. Child. 59: 222-229, 1984.">Poulos
et al. (1984)</a>; <a href="#Refsum1949" class="mim-tip-reference" title="Refsum, S., Salomonsen, L., Skatvedt, M. &lt;strong&gt;Heredopathia atactica polyneuritiformis in children.&lt;/strong&gt; J. Pediat. 35: 335-343, 1949.">Refsum et al. (1949)</a>; <a href="#Refsum1952" class="mim-tip-reference" title="Refsum, S. &lt;strong&gt;Heredopathia atactica polyneuritiformis.&lt;/strong&gt; J. Nerv. Ment. Dis. 116: 1046-1050, 1952.">Refsum (1952)</a>; <a href="#Refsum1981" class="mim-tip-reference" title="Refsum, S. &lt;strong&gt;Heredopathia atactica polyneuritiformis (phytanic-acid storage disease, Refsum&#x27;s disease): a biochemically well-defined disease with a specific dietary treatment.&lt;/strong&gt; Arch. Neurol. 38: 605-606, 1981.">Refsum (1981)</a>; <a href="#Richterich1965" class="mim-tip-reference" title="Richterich, R., van Mechelen, P., Rossi, E. &lt;strong&gt;Refsum&#x27;s disease (heredopathia atactica polyneuritiformis): an inborn error of lipid metabolism with storage of 3,7,11,15-tetramethyl hexadecanic acid. I. Report of a case.&lt;/strong&gt; Am. J. Med. 39: 230-236, 1965.">Richterich et al. (1965)</a>; <a href="#Steinberg1967" class="mim-tip-reference" title="Steinberg, D., Vroom, F. Q., Engel, W. K., Cammermeyer, J., Mize, C. E., Avigan, J. &lt;strong&gt;Refsum&#x27;s disease--a recently characterized lipidosis involving the nervous system.&lt;/strong&gt; Ann. Intern. Med. 66: 365-395, 1967.">Steinberg et al. (1967)</a>; <a href="#Steinberg1970" class="mim-tip-reference" title="Steinberg, D., Mize, C. E., Herndon, J. H., Jr., Fales, H. M., Engel, W. K., Vroom, F. Q. &lt;strong&gt;Phytanic acid in patients with Refsum&#x27;s syndrome and response to dietary treatment.&lt;/strong&gt; Arch. Intern. Med. 125: 75-87, 1970.">Steinberg et al.
(1970)</a>; <a href="#Steinberg1967" class="mim-tip-reference" title="Steinberg, D., Vroom, F. Q., Engel, W. K., Cammermeyer, J., Mize, C. E., Avigan, J. &lt;strong&gt;Refsum&#x27;s disease--a recently characterized lipidosis involving the nervous system.&lt;/strong&gt; Ann. Intern. Med. 66: 365-395, 1967.">Steinberg et al. (1967)</a>; <a href="#Watkins1994" class="mim-tip-reference" title="Watkins, P. A., Howard, A. E., Mihalik, S. J. &lt;strong&gt;Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes.&lt;/strong&gt; Biochim. Biophys. Acta 1214: 288-294, 1994.">Watkins et al. (1994)</a>; <a href="#Wierzbicki2000" class="mim-tip-reference" title="Wierzbicki, A. S., Mitchell, J., Lambert-Hammill, M., Hancock, M., Greenwood, J., Sidey, M. C., de Belleroche, J., Gibberd, F. B. &lt;strong&gt;Identification of genetic heterogeneity in Refsum&#x27;s disease.&lt;/strong&gt; Europ. J. Hum. Genet. 8: 649-651, 2000.">Wierzbicki et
al. (2000)</a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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</h4>
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</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
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<a id="Ashenhurst1958" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ashenhurst, E. M., Millar, J. H. D., Milliken, T. G.
<strong>Refsum's syndrome affecting a brother and two sisters.</strong>
Brit. Med. J. 2: 415-417, 1958.
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[<a href="https://doi.org/10.1136/bmj.2.5093.415" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Billimoria1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Billimoria, J. D., Clemens, M. E., Gibberd, F. B., Whitelaw, M. N.
<strong>Metabolism of phytanic acid in Refsum's disease.</strong>
Lancet 319: 194-196, 1982. Note: Originally Volume I.
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[<a href="https://doi.org/10.1016/s0140-6736(82)90760-7" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="3" class="mim-anchor"></a>
<a id="Braverman2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Braverman, N., Chen, L., Lin, P., Obie, C., Steel, G., Douglas, P., Chakraborty, P. K., Clarke, J. T. R., Boneh, A., Moser, A., Moser, H., Valle, D.
<strong>Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype.</strong>
Hum. Mutat. 20: 284-297, 2002.
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[<a href="https://doi.org/10.1002/humu.10124" target="_blank">Full Text</a>]
</p>
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</li>
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<a id="4" class="mim-anchor"></a>
<a id="Clark1951" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clark, D. B., Critchley, M.
<strong>Heredopathia atactica polyneuritiformis (Refsum's syndrome).</strong>
Proc. Roy. Soc. Med. 44: 689-690, 1951.
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</p>
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<li>
<a id="5" class="mim-anchor"></a>
<a id="Djupesland1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Djupesland, G., Flottorp, G., Refsum, S.
<strong>Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment.</strong>
Neurology 33: 237-240, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6185882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6185882</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6185882" 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.33.2.237" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
<a id="Eldjarn1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Eldjarn, L., Try, K., Stokke, O., Munthe-Kaas, A. W., Refsum, S., Steinberg, D., Avigan, J., Mize, C. E.
<strong>Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis.</strong>
Lancet 287: 691-693, 1966. Note: Originally Volume I.
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[<a href="https://doi.org/10.1016/s0140-6736(66)91632-1" target="_blank">Full Text</a>]
</p>
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<a id="7" class="mim-anchor"></a>
<a id="Gibberd1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibberd, F. B., Page, N. G. R., Billimoria, J. D., Retsas, S.
<strong>Heredopathia atactica polyneuritiformis (Refsum's disease) treated by diet and plasma-exchange.</strong>
Lancet 313: 575-578, 1979. Note: Originally Volume I.
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[<a href="https://doi.org/10.1016/s0140-6736(79)91005-5" target="_blank">Full Text</a>]
</p>
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<a id="8" class="mim-anchor"></a>
<a id="Herndon1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Herndon, J. H., Jr., Steinberg, D., Uhlendorf, B. W., Fales, H. M.
<strong>Refsum's disease: characterization of the enzyme defect in cell culture.</strong>
J. Clin. Invest. 48: 1017-1032, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4181593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4181593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4181593" 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/JCI106058" target="_blank">Full Text</a>]
</p>
</div>
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<a id="9" class="mim-anchor"></a>
<a id="Herndon1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Herndon, J. H., Jr., Steinberg, D., Uhlendorf, B. W.
<strong>Refsum's disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes.</strong>
New Eng. J. Med. 281: 1034-1038, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4188238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4188238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4188238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM196911062811903" target="_blank">Full Text</a>]
</p>
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<a id="Jansen2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jansen, G. A., Hogenhout, E. M., Ferdinandusse, S., Waterham, H. R., Ofman, R., Jakobs, C., Skjeldal, O. H., Wanders, R. J. A.
<strong>Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease.</strong>
Hum. Molec. Genet. 9: 1195-1200, 2000.
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[<a href="https://doi.org/10.1093/hmg/9.8.1195" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
<a id="Jansen1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jansen, G. A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., Besley, G. T. N., Wraith, J. E., Wanders, R. J. A.
<strong>Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng1097-190" target="_blank">Full Text</a>]
</p>
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<a id="12" class="mim-anchor"></a>
<a id="Jansen1997" class="mim-anchor"></a>
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<p class="mim-text-font">
Jansen, G. A., Wanders, R. J. A., Watkins, P. A., Mihalik, S. J.
<strong>Phytanoyl-coenzyme A hydroxylase deficiency--the enzyme defect in Refsum's disease. (Letter)</strong>
New Eng. J. Med. 337: 133-134, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9221344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9221344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9221344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199707103370215" target="_blank">Full Text</a>]
</p>
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<a id="Jansen2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jansen, G. A., Waterham, H. R., Wanders, R. J. A.
<strong>Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).</strong>
Hum. Mutat. 23: 209-218, 2004.
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[<a href="https://doi.org/10.1002/humu.10315" target="_blank">Full Text</a>]
</p>
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<a id="14" class="mim-anchor"></a>
<a id="Kahlke1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kahlke, W., Wagener, H.
<strong>Conversion of h3-phytol to phytanic acid and its incorporation into plasma lipid fractions in heredopathia atactica polyneuritiformis.</strong>
Metabolism 15: 687-693, 1966.
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[<a href="https://doi.org/10.1016/s0026-0495(66)80004-5" target="_blank">Full Text</a>]
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<a id="Klenk1963" class="mim-anchor"></a>
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<p class="mim-text-font">
Klenk, E., Kahlke, W.
<strong>Ueber das Vorkommen der 3.7.11.15-tetramethyl-hexadecansaeure (Phytansaeure) in den Cholesterinestern und anderen Lipoidfraktionen der Organe bei einem Krankheitsfall unbekannter Genese (Verdacht auf heredopathia atactica polyneuritiformis Refsum-syndrom).</strong>
Hoppe Seylers Z. Physiol. Chem. 333: 133-142, 1963.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14058273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14058273</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14058273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1515/bchm2.1963.333.1.133" target="_blank">Full Text</a>]
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<a id="Leys1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Leys, D., Petit, H., Bonte-Adnet, C., Millaire, A., Fourrier, F., Dubois, F., Rousseaux, M., Ducloux, G.
<strong>Refsum's disease revealed by cardiac disorders. (Letter)</strong>
Lancet 333: 621 only, 1989. Note: Originally Volume I.
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[<a href="https://doi.org/10.1016/s0140-6736(89)91654-1" target="_blank">Full Text</a>]
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<a id="Mihalik1997" class="mim-anchor"></a>
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Mihalik, S. J., Morrell, J. C., Kim. D., Sacksteder, K. A., Watkins, P. A., Gould, S. J.
<strong>Identification of PAHX, a Refsum disease gene.</strong>
Nature Genet. 17: 185-189, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng1097-185" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Mize1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Mize, C. E., Herndon, J. H., Jr., Blass, J. P., Milne, G. W. A., Follansbee, C., Laudat, P., Steinberg, D.
<strong>Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease.</strong>
J. Clin. Invest. 48: 1033-1040, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4181594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4181594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4181594" 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/JCI106059" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Moser1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Moser, H. W., Braine, H., Pyeritz, R. E., Ullman, D. D., Murray, C., Asbury, A. K.
<strong>Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease.</strong>
Birth Defects Orig. Art. Ser. 16(1): 491-497, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6160883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6160883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6160883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Nadal1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nadal, N., Rolland, M.-O., Tranchant, C., Reutenauer, L., Gyapay, G., Warter, J.-M., Mandel, J.-L., Koenig, M.
<strong>Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family.</strong>
Hum. Molec. Genet. 4: 1963-1966, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8595422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/4.10.1963" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Nyberg-Hansen1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nyberg-Hansen, R.
<strong>Obituary: Sigvald Refsum (1907-1991).</strong>
J. Neurol. Sci. 107: 125-126, 1992.
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Poulos1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Poulos, A., Pollard, A. C., Mitchell, J. D., Wise, G., Mortimer, G.
<strong>Patterns of Refsum's disease: phytanic acid oxidase deficiency.</strong>
Arch. Dis. Child. 59: 222-229, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6201142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6201142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6201142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.59.3.222" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Refsum1949" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Refsum, S., Salomonsen, L., Skatvedt, M.
<strong>Heredopathia atactica polyneuritiformis in children.</strong>
J. Pediat. 35: 335-343, 1949.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18140089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18140089</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18140089" 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(49)80006-0" target="_blank">Full Text</a>]
</p>
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<a id="24" class="mim-anchor"></a>
<a id="Refsum1946" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathica atactica polyneuritiformis: a familial syndrome not hitherto described.</strong>
Acta Psychiat. Scand. Suppl. 38: :1-303, 1946.
</p>
</div>
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<li>
<a id="25" class="mim-anchor"></a>
<a id="Refsum1952" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathia atactica polyneuritiformis.</strong>
J. Nerv. Ment. Dis. 116: 1046-1050, 1952.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13045168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13045168</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13045168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00005053-195212000-00051" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="26" class="mim-anchor"></a>
<a id="Refsum1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathia atactica polyneuritiformis (phytanic-acid storage disease, Refsum's disease): a biochemically well-defined disease with a specific dietary treatment.</strong>
Arch. Neurol. 38: 605-606, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6170281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6170281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6170281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1981.00510100033003" target="_blank">Full Text</a>]
</p>
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<li>
<a id="27" class="mim-anchor"></a>
<a id="Richterich1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Richterich, R., van Mechelen, P., Rossi, E.
<strong>Refsum's disease (heredopathia atactica polyneuritiformis): an inborn error of lipid metabolism with storage of 3,7,11,15-tetramethyl hexadecanic acid. I. Report of a case.</strong>
Am. J. Med. 39: 230-236, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14320689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14320689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14320689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9343(65)90046-x" target="_blank">Full Text</a>]
</p>
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<li>
<a id="28" class="mim-anchor"></a>
<a id="Robertson1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robertson, E. F., Poulos, A., Sharp, P., Manson, J., Wise, G., Jaunzems, A., Carter, R.
<strong>Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.</strong>
Europ. J. Pediat. 147: 133-142, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2452736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2452736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2452736" 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/BF00442210" target="_blank">Full Text</a>]
</p>
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<a id="29" class="mim-anchor"></a>
<a id="Skjeldal1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H.
<strong>Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.</strong>
J. Neurol. Sci. 77: 87-96, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2433405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2433405</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2433405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(87)90209-7" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="30" class="mim-anchor"></a>
<a id="Steinberg1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinberg, D., Herndon, J. H., Jr., Uhlendorf, B. W., Mize, C. E., Avigan, J., Milne, G. W. A.
<strong>Refsum's disease: nature of the enzyme defect.</strong>
Science 156: 1740-1742, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4180573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4180573</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4180573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.156.3783.1740" target="_blank">Full Text</a>]
</p>
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<a id="31" class="mim-anchor"></a>
<a id="Steinberg1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinberg, D., Mize, C. E., Avigan, J., Fales, H. M., Eldjarn, L., Try, K., Stokke, O., Refsum, S.
<strong>Studies on the metabolic error in Refsum's disease.</strong>
J. Clin. Invest. 46: 313-322, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4164676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4164676</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4164676" 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/JCI105533" target="_blank">Full Text</a>]
</p>
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<a id="32" class="mim-anchor"></a>
<a id="Steinberg1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinberg, D., Mize, C. E., Herndon, J. H., Jr., Fales, H. M., Engel, W. K., Vroom, F. Q.
<strong>Phytanic acid in patients with Refsum's syndrome and response to dietary treatment.</strong>
Arch. Intern. Med. 125: 75-87, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4188898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4188898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4188898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<li>
<a id="33" class="mim-anchor"></a>
<a id="Steinberg1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinberg, D., Vroom, F. Q., Engel, W. K., Cammermeyer, J., Mize, C. E., Avigan, J.
<strong>Refsum's disease--a recently characterized lipidosis involving the nervous system.</strong>
Ann. Intern. Med. 66: 365-395, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4163283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4163283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4163283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.7326/0003-4819-66-2-365" target="_blank">Full Text</a>]
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<a id="34" class="mim-anchor"></a>
<a id="Steinberg1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinberg, D.
<strong>Personal Communication.</strong>
La Jolla, Calif. 2/1982.
</p>
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<li>
<a id="35" class="mim-anchor"></a>
<a id="Tranchant1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tranchant, C., Aubourg, P., Mohr, M., Rocchiccioli, F., Zaenker, C., Warter, J. M.
<strong>A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.</strong>
Neurology 43: 2044-2048, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8413964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8413964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8413964" 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.43.10.2044" target="_blank">Full Text</a>]
</p>
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<a id="36" class="mim-anchor"></a>
<a id="Watkins1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Watkins, P. A., Howard, A. E., Mihalik, S. J.
<strong>Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes.</strong>
Biochim. Biophys. Acta 1214: 288-294, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7918611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7918611</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7918611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0005-2760(94)90075-2" target="_blank">Full Text</a>]
</p>
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<a id="37" class="mim-anchor"></a>
<a id="Wierzbicki2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wierzbicki, A. S., Mitchell, J., Lambert-Hammill, M., Hancock, M., Greenwood, J., Sidey, M. C., de Belleroche, J., Gibberd, F. B.
<strong>Identification of genetic heterogeneity in Refsum's disease.</strong>
Europ. J. Hum. Genet. 8: 649-651, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10951529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10951529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10951529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/sj.ejhg.5200511" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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Cassandra L. Kniffin - reorganized : 11/25/2009
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Cassandra L. Kniffin - updated : 11/19/2009<br>Victor A. McKusick - updated : 4/7/2004<br>Victor A. McKusick - updated : 2/27/2003<br>Victor A. McKusick - updated : 11/21/2002<br>Victor A. McKusick - updated : 11/2/2000<br>Victor A. McKusick - updated : 9/30/1997<br>Victor A. McKusick - updated : 9/8/1997<br>Orest Hurko - updated : 3/22/1996
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Creation Date:
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Victor A. McKusick : 6/4/1986
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alopez : 02/01/2024
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alopez : 02/02/2017<br>joanna : 08/04/2015<br>alopez : 10/25/2012<br>alopez : 10/25/2012<br>alopez : 10/24/2012<br>terry : 10/6/2011<br>carol : 11/25/2009<br>ckniffin : 11/19/2009<br>terry : 3/24/2009<br>terry : 3/24/2009<br>ckniffin : 12/17/2007<br>terry : 3/3/2005<br>ckniffin : 5/12/2004<br>tkritzer : 4/12/2004<br>terry : 4/7/2004<br>tkritzer : 9/17/2003<br>carol : 3/4/2003<br>tkritzer : 3/3/2003<br>terry : 2/27/2003<br>cwells : 11/21/2002<br>terry : 11/20/2002<br>mcapotos : 11/16/2000<br>mcapotos : 11/14/2000<br>terry : 11/2/2000<br>terry : 10/13/1999<br>terry : 6/5/1998<br>dholmes : 10/3/1997<br>jenny : 9/30/1997<br>terry : 9/26/1997<br>jenny : 9/18/1997<br>terry : 9/8/1997<br>terry : 9/8/1997<br>terry : 4/15/1996<br>mark : 3/22/1996<br>mark : 3/22/1996<br>terry : 3/14/1996<br>davew : 8/19/1994<br>warfield : 4/20/1994<br>mimadm : 3/29/1994<br>carol : 5/12/1992<br>carol : 3/31/1992<br>supermim : 3/17/1992
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<h3>
<span class="mim-font">
<strong>#</strong> 266500
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<h3>
<span class="mim-font">
REFSUM DISEASE, CLASSIC
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<br />
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<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
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<h4>
<span class="mim-font">
REFSUM DISEASE, ADULT, 1<br />
PHYTANIC ACID OXIDASE DEFICIENCY<br />
HEREDOPATHIA ATACTICA POLYNEURITIFORMIS<br />
HEREDITARY MOTOR AND SENSORY NEUROPATHY IV; HMSN4<br />
HMSN IV
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<strong>SNOMEDCT:</strong> 25362006; &nbsp;
<strong>ICD10CM:</strong> G60.1; &nbsp;
<strong>ICD9CM:</strong> 356.3; &nbsp;
<strong>ORPHA:</strong> 773; &nbsp;
<strong>DO:</strong> 10582; &nbsp;
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<h4>
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<th>
Location
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<th>
Phenotype
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<th>
Phenotype <br /> MIM number
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<th>
Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<td>
<span class="mim-font">
10p13
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<span class="mim-font">
Refsum disease
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<span class="mim-font">
266500
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<span class="mim-font">
Autosomal recessive
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<span class="mim-font">
3
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<span class="mim-font">
PHYH
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<span class="mim-font">
602026
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<span class="mim-font">
<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that classic Refsum disease is caused by homozygous or compound hterozygous mutation in the gene encoding phytanoyl-CoA hydroxylase (PHYH, or PAHX; 602026) on chromosome 10p13.</p>
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<strong>Description</strong>
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<p>Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia (review by Skjeldal et al., 1987). </p><p>Increased levels of phytanic acid can also be found in peroxisomal biogenesis disorders; see Zellweger syndrome (see 214100) (Skjeldal et al., 1987). </p><p>Infantile Refsum disease (see PBD1B, 601539) is a distinct disorder with a different phenotype and genetic basis.</p><p>A phenotype clinically indistinguishable from that of classic Refsum disease (PBD9B; 614879), but with a different biochemical profile, can be caused by mutation in the gene encoding peroxin-7 (PEX7; 601757) on chromosome 6q.</p>
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<strong>Clinical Features</strong>
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<p>Refsum (1946) first described this disorder and noted the hereditary aspect.</p><p>Skjeldal et al. (1987) reported the clinical features of 17 patients with Refsum disease. Although onset of symptoms was reportedly insidious, they generally were reported to occur late in the first decade through the third decade of life. All patients had retinitis pigmentosa with night blindness and constriction of the visual fields, and many patients had cataracts. All had some sign of polyneuropathy, most commonly impaired reflexes, and most patients also had sensory disturbances and limb paresis or atrophy. Only 5 patients had clear cerebellar ataxia. Other common features included anosmia and progressive hearing loss. Skin changes, cardiac abnormalities, and skeletal manifestations were less common. Serum phytanic acid was increased in those who had not been treated by diet, and phytanic acid oxidase activity in fibroblasts was very low. </p><p>Leys et al. (1989) described 2 brothers who presented in their twenties with severe heart failure as the predominant clinical manifestation of Refsum disease. Both of them had retinitis pigmentosa with lack of ERG response, miosis, anosmia, and bilateral shortening of the fourth metatarsals, but no cataracts or deafness. One of them had mild bilateral ptosis. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of classic Refsum disease in the family of patients 1 and 2 reported by Jansen et al. (1997) was consistent with autosomal recessive inheritance. </p>
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<strong>Biochemical Features</strong>
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<p>Klenk and Kahlke (1963) discovered that patients with hereditary ataxia and polyneuritis of the Refsum type have accumulation of the phytanic acid, an unusual branched-chain fatty acid (3,7,11,15-tetramethyl-hexadecanoic acid), in tissues and body fluids. Further studies showed that the defect in Refsum disease involves lack of proper degradation of phytanic acid, which is exclusively derived from exogenous sources. Exogenous phytol is readily converted to phytanic acid. </p><p>Steinberg et al. (1967) found that cultured fibroblasts from patients with Refsum disease showed very low oxidation of C14-labeled phytanic acid, but normal oxidation of pristanic acid, which is known to be the first product of phytanic acid degradation. The authors concluded that the defect resides in the enzyme that catalyzes the alpha-oxidative process by which phytanic acid is shortened by one carbon atom. Studies of cultured fibroblasts from patients with Refsum disease also led Herndon et al. (1969) to the conclusion that the enzyme involved in alpha-hydroxylation of phytanate is deficient, whereas enzymes involved in later steps are normal. Steinberg (1982) suggested that the enzyme deficient in this disorder may be a mixed-function oxygenase. </p><p>Jansen et al. (1997) noted that phytanic acid normally undergoes alpha-oxidation in which the chain is shortened by 1 carbon atom, yielding pristanic acid and carbon dioxide. Pristanic acid can be degraded by beta-oxidation to yield 3 molecules of acetyl-coenzyme A (CoA), 3 of propionyl-CoA, and 1 of isobutyryl-CoA. Patients with Refsum disease have deficient alpha-oxidation of (14)C-phytanic acid to pristanic acid, whereas the subsequent beta-oxidation of pristanic acid is normal. Jansen et al. (1997) reported that phytanoyl-CoA hydroxylase activity was undetectable in liver tissue from a patient with Refsum disease. On the basis of these findings, they stated that Refsum disease can be classified as a true peroxisomal disorder. </p><p>Mihalik et al. (1997) observed that decreased phytanic-acid oxidation is also observed in human cells lacking PEX7 (601757), the receptor for the type 2 peroxisomal targeting signal (PTS2), suggesting that the enzyme defective in Refsum disease is targeted to peroxisomes by a PTS2. </p><p>Tranchant et al. (1993) described 4 patients with adult Refsum disease having, in addition to the usual biochemical features, accumulation of L-pipecolic acid, another metabolite (derived from L-lysine) catabolized in peroxisomes. The youngest brother died at age 17 from a rapidly progressing neurologic deterioration, suggesting that the patients may suffer from a peroxisomal disorder intermediate between infantile Refsum disease and adult Refsum disease. Nadal et al. (1995) referred to this disorder as Refsum disease with increased pipecolic acidemia. </p>
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<h4>
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<strong>Clinical Management</strong>
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<p>Eldjarn et al. (1966) showed that with a diet free of chlorophyll and of foods which might contain phytol, phytanic acid, or their precursors, phytanic acid could be reduced in the blood and clinical improvement effected. Plasmapheresis performed once or twice a month effectively removes phytanic acid from the body and permits liberalization of dietary restriction while preventing progression of the clinical features (Gibberd et al., 1979; Moser et al., 1980). </p><p>Robertson et al. (1988) treated 2 patients with low phytanic acid diet and reported a decrease in plasma phytanic acid levels, a marked decrease in plasma pipecolic acid, and a relatively slow decrease in the C26-C22 fatty acid ratios, which remained markedly abnormal even after 2 years. Clinical data suggested stabilization or perhaps slight improvement. </p>
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<strong>Mapping</strong>
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<p>Nadal et al. (1995) localized the Refsum disease gene to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family. The PHYH gene maps to this region (Mihalik et al., 1997). </p><p>Nadal et al. (1995) performed genomewide linkage analysis in the family described by Tranchant et al. (1993) with increased pipecolic acidemia and demonstrated linkage with significant lod score values by the combination of 3 independent sources of information: multiple affected sibs, first-degree consanguinity, and biochemical discrimination between healthy heterozygous carriers and noncarriers. The study illustrated the power of a dense map of microsatellite markers combined with classic linkage analysis and homozygosity mapping. They obtained a lod score of 3.6 between the phenotype and the interval defined by D10S249 and D10S466 on 10p in this single consanguineous family. Since this disorder maps to the same site at the tip of the short arm of chromosome 10 where the gene for phytanoyl-CoA hydroxylase (PHYH) also maps, and since the PHYH gene is the site of mutations in classic Refsum disease, mutations in that gene should be sought in these cases. </p>
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<span class="mim-font">
<strong>Molecular Genetics</strong>
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<p>Mihalik et al. (1997) found that both Refsum disease patients examined were homozygous for inactivating mutations in the PHYH gene (602026.0001 and 602026.0002). </p><p>Independently, Jansen et al. (1997) identified mutations in the PHYH gene in 5 patients with Refsum disease, including a 1-bp deletion, a 111-bp deletion, and a point mutation (602026.0002-602026.0004). Some of the patients had been reported by Skjeldal et al. (1987). </p><p>In 22 patients with Refsum disease, Jansen et al. (2000) identified mutations in the PHYH gene, including 14 different missense mutations, a 3-bp insertion, and a 1-bp deletion, which were all confirmed at the genome level (see, e.g., 602026.0005-602026.0009). A 111-bp deletion (602026.0002) identified in the PHYH cDNA of several patients with Refsum disease was due to either 1 of 2 different mutations in the same splice acceptor site, which result in skipping of exon 3. Six mutations were expressed in S. cerevisiae, and all led to an enzymatically inactive PhyH protein. </p>
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<h4>
<span class="mim-font">
<strong>Nomenclature</strong>
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</h4>
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<span class="mim-text-font">
<p>The designation 'infantile Refsum disease' (see 601539), or infantile phytanic acid storage disease, was used for a congenital disorder with some clinical features resembling Refsum disease and with phytanic acid accumulation. However, since it subsequently proved to be a peroxisome biogenesis disorder, Jansen et al. (2004) suggested that the designation is unfortunate and should be discarded. </p>
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<h4>
<span class="mim-font">
<strong>History</strong>
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<span class="mim-text-font">
<p>Nyberg-Hansen (1992) provided an obituary of Sigvald Refsum, 1907-1991.</p>
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<span class="mim-font">
<strong>See Also:</strong>
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Ashenhurst et al. (1958); Billimoria et al. (1982); Braverman et al.
(2002); Clark and Critchley (1951); Djupesland et al. (1983); Herndon
et al. (1969); Kahlke and Wagener (1966); Mize et al. (1969); Poulos
et al. (1984); Refsum et al. (1949); Refsum (1952); Refsum (1981);
Richterich et al. (1965); Steinberg et al. (1967); Steinberg et al.
(1970); Steinberg et al. (1967); Watkins et al. (1994); Wierzbicki et
al. (2000)
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
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<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Ashenhurst, E. M., Millar, J. H. D., Milliken, T. G.
<strong>Refsum&#x27;s syndrome affecting a brother and two sisters.</strong>
Brit. Med. J. 2: 415-417, 1958.
[PubMed: 13560885]
[Full Text: https://doi.org/10.1136/bmj.2.5093.415]
</p>
</li>
<li>
<p class="mim-text-font">
Billimoria, J. D., Clemens, M. E., Gibberd, F. B., Whitelaw, M. N.
<strong>Metabolism of phytanic acid in Refsum&#x27;s disease.</strong>
Lancet 319: 194-196, 1982. Note: Originally Volume I.
[PubMed: 6172683]
[Full Text: https://doi.org/10.1016/s0140-6736(82)90760-7]
</p>
</li>
<li>
<p class="mim-text-font">
Braverman, N., Chen, L., Lin, P., Obie, C., Steel, G., Douglas, P., Chakraborty, P. K., Clarke, J. T. R., Boneh, A., Moser, A., Moser, H., Valle, D.
<strong>Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype.</strong>
Hum. Mutat. 20: 284-297, 2002.
[PubMed: 12325024]
[Full Text: https://doi.org/10.1002/humu.10124]
</p>
</li>
<li>
<p class="mim-text-font">
Clark, D. B., Critchley, M.
<strong>Heredopathia atactica polyneuritiformis (Refsum&#x27;s syndrome).</strong>
Proc. Roy. Soc. Med. 44: 689-690, 1951.
[PubMed: 19993784]
</p>
</li>
<li>
<p class="mim-text-font">
Djupesland, G., Flottorp, G., Refsum, S.
<strong>Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment.</strong>
Neurology 33: 237-240, 1983.
[PubMed: 6185882]
[Full Text: https://doi.org/10.1212/wnl.33.2.237]
</p>
</li>
<li>
<p class="mim-text-font">
Eldjarn, L., Try, K., Stokke, O., Munthe-Kaas, A. W., Refsum, S., Steinberg, D., Avigan, J., Mize, C. E.
<strong>Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis.</strong>
Lancet 287: 691-693, 1966. Note: Originally Volume I.
[PubMed: 4159604]
[Full Text: https://doi.org/10.1016/s0140-6736(66)91632-1]
</p>
</li>
<li>
<p class="mim-text-font">
Gibberd, F. B., Page, N. G. R., Billimoria, J. D., Retsas, S.
<strong>Heredopathia atactica polyneuritiformis (Refsum&#x27;s disease) treated by diet and plasma-exchange.</strong>
Lancet 313: 575-578, 1979. Note: Originally Volume I.
[PubMed: 85164]
[Full Text: https://doi.org/10.1016/s0140-6736(79)91005-5]
</p>
</li>
<li>
<p class="mim-text-font">
Herndon, J. H., Jr., Steinberg, D., Uhlendorf, B. W., Fales, H. M.
<strong>Refsum&#x27;s disease: characterization of the enzyme defect in cell culture.</strong>
J. Clin. Invest. 48: 1017-1032, 1969.
[PubMed: 4181593]
[Full Text: https://doi.org/10.1172/JCI106058]
</p>
</li>
<li>
<p class="mim-text-font">
Herndon, J. H., Jr., Steinberg, D., Uhlendorf, B. W.
<strong>Refsum&#x27;s disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes.</strong>
New Eng. J. Med. 281: 1034-1038, 1969.
[PubMed: 4188238]
[Full Text: https://doi.org/10.1056/NEJM196911062811903]
</p>
</li>
<li>
<p class="mim-text-font">
Jansen, G. A., Hogenhout, E. M., Ferdinandusse, S., Waterham, H. R., Ofman, R., Jakobs, C., Skjeldal, O. H., Wanders, R. J. A.
<strong>Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum&#x27;s disease.</strong>
Hum. Molec. Genet. 9: 1195-1200, 2000.
[PubMed: 10767344]
[Full Text: https://doi.org/10.1093/hmg/9.8.1195]
</p>
</li>
<li>
<p class="mim-text-font">
Jansen, G. A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., Besley, G. T. N., Wraith, J. E., Wanders, R. J. A.
<strong>Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.</strong>
Nature Genet. 17: 190-193, 1997.
[PubMed: 9326940]
[Full Text: https://doi.org/10.1038/ng1097-190]
</p>
</li>
<li>
<p class="mim-text-font">
Jansen, G. A., Wanders, R. J. A., Watkins, P. A., Mihalik, S. J.
<strong>Phytanoyl-coenzyme A hydroxylase deficiency--the enzyme defect in Refsum&#x27;s disease. (Letter)</strong>
New Eng. J. Med. 337: 133-134, 1997.
[PubMed: 9221344]
[Full Text: https://doi.org/10.1056/NEJM199707103370215]
</p>
</li>
<li>
<p class="mim-text-font">
Jansen, G. A., Waterham, H. R., Wanders, R. J. A.
<strong>Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).</strong>
Hum. Mutat. 23: 209-218, 2004.
[PubMed: 14974078]
[Full Text: https://doi.org/10.1002/humu.10315]
</p>
</li>
<li>
<p class="mim-text-font">
Kahlke, W., Wagener, H.
<strong>Conversion of h3-phytol to phytanic acid and its incorporation into plasma lipid fractions in heredopathia atactica polyneuritiformis.</strong>
Metabolism 15: 687-693, 1966.
[PubMed: 4166674]
[Full Text: https://doi.org/10.1016/s0026-0495(66)80004-5]
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</li>
<li>
<p class="mim-text-font">
Klenk, E., Kahlke, W.
<strong>Ueber das Vorkommen der 3.7.11.15-tetramethyl-hexadecansaeure (Phytansaeure) in den Cholesterinestern und anderen Lipoidfraktionen der Organe bei einem Krankheitsfall unbekannter Genese (Verdacht auf heredopathia atactica polyneuritiformis Refsum-syndrom).</strong>
Hoppe Seylers Z. Physiol. Chem. 333: 133-142, 1963.
[PubMed: 14058273]
[Full Text: https://doi.org/10.1515/bchm2.1963.333.1.133]
</p>
</li>
<li>
<p class="mim-text-font">
Leys, D., Petit, H., Bonte-Adnet, C., Millaire, A., Fourrier, F., Dubois, F., Rousseaux, M., Ducloux, G.
<strong>Refsum&#x27;s disease revealed by cardiac disorders. (Letter)</strong>
Lancet 333: 621 only, 1989. Note: Originally Volume I.
[PubMed: 2466186]
[Full Text: https://doi.org/10.1016/s0140-6736(89)91654-1]
</p>
</li>
<li>
<p class="mim-text-font">
Mihalik, S. J., Morrell, J. C., Kim. D., Sacksteder, K. A., Watkins, P. A., Gould, S. J.
<strong>Identification of PAHX, a Refsum disease gene.</strong>
Nature Genet. 17: 185-189, 1997.
[PubMed: 9326939]
[Full Text: https://doi.org/10.1038/ng1097-185]
</p>
</li>
<li>
<p class="mim-text-font">
Mize, C. E., Herndon, J. H., Jr., Blass, J. P., Milne, G. W. A., Follansbee, C., Laudat, P., Steinberg, D.
<strong>Localization of the oxidative defect in phytanic acid degradation in patients with Refsum&#x27;s disease.</strong>
J. Clin. Invest. 48: 1033-1040, 1969.
[PubMed: 4181594]
[Full Text: https://doi.org/10.1172/JCI106059]
</p>
</li>
<li>
<p class="mim-text-font">
Moser, H. W., Braine, H., Pyeritz, R. E., Ullman, D. D., Murray, C., Asbury, A. K.
<strong>Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease.</strong>
Birth Defects Orig. Art. Ser. 16(1): 491-497, 1980.
[PubMed: 6160883]
</p>
</li>
<li>
<p class="mim-text-font">
Nadal, N., Rolland, M.-O., Tranchant, C., Reutenauer, L., Gyapay, G., Warter, J.-M., Mandel, J.-L., Koenig, M.
<strong>Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family.</strong>
Hum. Molec. Genet. 4: 1963-1966, 1995.
[PubMed: 8595422]
[Full Text: https://doi.org/10.1093/hmg/4.10.1963]
</p>
</li>
<li>
<p class="mim-text-font">
Nyberg-Hansen, R.
<strong>Obituary: Sigvald Refsum (1907-1991).</strong>
J. Neurol. Sci. 107: 125-126, 1992.
</p>
</li>
<li>
<p class="mim-text-font">
Poulos, A., Pollard, A. C., Mitchell, J. D., Wise, G., Mortimer, G.
<strong>Patterns of Refsum&#x27;s disease: phytanic acid oxidase deficiency.</strong>
Arch. Dis. Child. 59: 222-229, 1984.
[PubMed: 6201142]
[Full Text: https://doi.org/10.1136/adc.59.3.222]
</p>
</li>
<li>
<p class="mim-text-font">
Refsum, S., Salomonsen, L., Skatvedt, M.
<strong>Heredopathia atactica polyneuritiformis in children.</strong>
J. Pediat. 35: 335-343, 1949.
[PubMed: 18140089]
[Full Text: https://doi.org/10.1016/s0022-3476(49)80006-0]
</p>
</li>
<li>
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathica atactica polyneuritiformis: a familial syndrome not hitherto described.</strong>
Acta Psychiat. Scand. Suppl. 38: :1-303, 1946.
</p>
</li>
<li>
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathia atactica polyneuritiformis.</strong>
J. Nerv. Ment. Dis. 116: 1046-1050, 1952.
[PubMed: 13045168]
[Full Text: https://doi.org/10.1097/00005053-195212000-00051]
</p>
</li>
<li>
<p class="mim-text-font">
Refsum, S.
<strong>Heredopathia atactica polyneuritiformis (phytanic-acid storage disease, Refsum&#x27;s disease): a biochemically well-defined disease with a specific dietary treatment.</strong>
Arch. Neurol. 38: 605-606, 1981.
[PubMed: 6170281]
[Full Text: https://doi.org/10.1001/archneur.1981.00510100033003]
</p>
</li>
<li>
<p class="mim-text-font">
Richterich, R., van Mechelen, P., Rossi, E.
<strong>Refsum&#x27;s disease (heredopathia atactica polyneuritiformis): an inborn error of lipid metabolism with storage of 3,7,11,15-tetramethyl hexadecanic acid. I. Report of a case.</strong>
Am. J. Med. 39: 230-236, 1965.
[PubMed: 14320689]
[Full Text: https://doi.org/10.1016/0002-9343(65)90046-x]
</p>
</li>
<li>
<p class="mim-text-font">
Robertson, E. F., Poulos, A., Sharp, P., Manson, J., Wise, G., Jaunzems, A., Carter, R.
<strong>Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.</strong>
Europ. J. Pediat. 147: 133-142, 1988.
[PubMed: 2452736]
[Full Text: https://doi.org/10.1007/BF00442210]
</p>
</li>
<li>
<p class="mim-text-font">
Skjeldal, O. H., Stokke, O., Refsum, S., Norseth, J., Petit, H.
<strong>Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.</strong>
J. Neurol. Sci. 77: 87-96, 1987.
[PubMed: 2433405]
[Full Text: https://doi.org/10.1016/0022-510x(87)90209-7]
</p>
</li>
<li>
<p class="mim-text-font">
Steinberg, D., Herndon, J. H., Jr., Uhlendorf, B. W., Mize, C. E., Avigan, J., Milne, G. W. A.
<strong>Refsum&#x27;s disease: nature of the enzyme defect.</strong>
Science 156: 1740-1742, 1967.
[PubMed: 4180573]
[Full Text: https://doi.org/10.1126/science.156.3783.1740]
</p>
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Steinberg, D., Mize, C. E., Avigan, J., Fales, H. M., Eldjarn, L., Try, K., Stokke, O., Refsum, S.
<strong>Studies on the metabolic error in Refsum&#x27;s disease.</strong>
J. Clin. Invest. 46: 313-322, 1967.
[PubMed: 4164676]
[Full Text: https://doi.org/10.1172/JCI105533]
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Steinberg, D., Mize, C. E., Herndon, J. H., Jr., Fales, H. M., Engel, W. K., Vroom, F. Q.
<strong>Phytanic acid in patients with Refsum&#x27;s syndrome and response to dietary treatment.</strong>
Arch. Intern. Med. 125: 75-87, 1970.
[PubMed: 4188898]
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Steinberg, D., Vroom, F. Q., Engel, W. K., Cammermeyer, J., Mize, C. E., Avigan, J.
<strong>Refsum&#x27;s disease--a recently characterized lipidosis involving the nervous system.</strong>
Ann. Intern. Med. 66: 365-395, 1967.
[PubMed: 4163283]
[Full Text: https://doi.org/10.7326/0003-4819-66-2-365]
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Steinberg, D.
<strong>Personal Communication.</strong>
La Jolla, Calif. 2/1982.
</p>
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Tranchant, C., Aubourg, P., Mohr, M., Rocchiccioli, F., Zaenker, C., Warter, J. M.
<strong>A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.</strong>
Neurology 43: 2044-2048, 1993.
[PubMed: 8413964]
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Watkins, P. A., Howard, A. E., Mihalik, S. J.
<strong>Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes.</strong>
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Wierzbicki, A. S., Mitchell, J., Lambert-Hammill, M., Hancock, M., Greenwood, J., Sidey, M. C., de Belleroche, J., Gibberd, F. B.
<strong>Identification of genetic heterogeneity in Refsum&#x27;s disease.</strong>
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