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<title>
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Entry
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- #256730 - CEROID LIPOFUSCINOSIS, NEURONAL, 1; CLN1
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- OMIM
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<span class="h4">#256730</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/256730"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS256730"> <strong>Phenotypic Series</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="#nomenclature">Nomenclature</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#diagnosis">Diagnosis</a>
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<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#pathogenesis">Pathogenesis</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#populationGenetics">Population Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(CEROID LIPOFUSCINOSIS, NEURONAL) OR (PPT1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/1250" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228329" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="http://www.informatics.jax.org/disease/256730" 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>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001311,001504" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0110721" 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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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:256730" 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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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<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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</span>
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</span>
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</div>
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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">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 58258004<br />
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<strong>ORPHA:</strong> 228329<br />
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<strong>DO:</strong> 0110721<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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256730
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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CEROID LIPOFUSCINOSIS, NEURONAL, 1; CLN1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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NEURONAL CEROID LIPOFUSCINOSIS, INFANTILE, INCLUDED; INCL, INCLUDED
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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SANTAVUORI DISEASE, INCLUDED<br />
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SANTAVUORI-HALTIA DISEASE, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/484?start=-3&limit=10&highlight=484">
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1p34.2
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Ceroid lipofuscinosis, neuronal, 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/256730"> 256730 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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PPT1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/600722"> 600722 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/256730" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS256730" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<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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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/256730" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/256730" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> INHERITANCE </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
|
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- 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 />
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly, postnatal, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000253" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000253</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000253" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000253</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Vision loss, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839364&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839364</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000529" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000529</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000529" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000529</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397540003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H54.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H54.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/369.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">369.9</a>]</span><br /> -
|
|
Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</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 /> -
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Macular degeneration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422338006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422338006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267718000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267718000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H35.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H35.30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/362.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">362.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242383</a>, <a href="https://bioportal.bioontology.org/search?q=C0024437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000608" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000608</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000608" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000608</a>]</span><br /> -
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Blindness by age 2 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850457&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850457</a>]</span><br /> -
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Reduced or abolished electroretinogram (ERG) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850458&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850458</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000654</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> SKELETAL </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Limbs </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Flexion contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88565003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88565003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203598005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203598005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/785817002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">785817002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/385522000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">385522000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333068&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333068</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Psychomotor degeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836842&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836842</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002361" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002361</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002361" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002361</a>]</span><br /> -
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Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
|
|
Cognitive decline in older patients <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2678465&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2678465</a>]</span><br /> -
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|
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
|
Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
|
|
Myoclonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17450006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17450006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/333.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">333.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027066</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span><br /> -
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|
Loss of speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542223&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542223</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span><br /> -
|
|
Electroencephalogram (EEG) abnormalities <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274521009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274521009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R94.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R94.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151611</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002353" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002353</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002353" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002353</a>]</span><br /> -
|
|
Cerebral atrophy, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864928&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864928</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
|
|
Hypointensity of the thalami early-on seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231064&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231064</a>]</span><br /> -
|
|
High signal intensity of the white matter later seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231063</a>]</span><br /> -
|
|
Autofluorescent lipopigment in neurons <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864678</a>]</span><br /> -
|
|
Granular material in neurons <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850455&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850455</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Behavioral Psychiatric Manifestations </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Irritability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55929007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55929007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022107</a>, <a href="https://bioportal.bioontology.org/search?q=C2700617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2700617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span><br /> -
|
|
Sleep disturbances <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39898005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39898005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53888004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53888004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G47" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G47</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G47.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G47.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.5</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/780.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037317&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037317</a>, <a href="https://bioportal.bioontology.org/search?q=C0851578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0851578</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002360</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002360</a>]</span><br /> -
|
|
Hyperexcitability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0856984&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0856984</a>, <a href="https://bioportal.bioontology.org/search?q=C0814034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0814034</a>]</span><br /> -
|
|
Depression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78667006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78667006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35489007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35489007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366979004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366979004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255339005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255339005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F34.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F34.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F32.A" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F32.A</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F33.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F33.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0812393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0812393</a>, <a href="https://bioportal.bioontology.org/search?q=C0011581&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011581</a>, <a href="https://bioportal.bioontology.org/search?q=C0460137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0460137</a>, <a href="https://bioportal.bioontology.org/search?q=C1579931&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1579931</a>, <a href="https://bioportal.bioontology.org/search?q=C0344315&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344315</a>, <a href="https://bioportal.bioontology.org/search?q=C4085311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4085311</a>, <a href="https://bioportal.bioontology.org/search?q=C0011570&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011570</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</a>]</span><br /> -
|
|
Hallucinations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7011001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7011001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R44.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R44.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018524</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000738</a>]</span><br />
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|
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</span>
|
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</div>
|
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</div>
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</div>
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</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Granular osmiophilic cytoplasmic deposits (GROD) ultrastructurally in cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850459&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850459</a>]</span><br /> -
|
|
Decreased activity of PPT1 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850460&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850460</a>]</span><br /> -
|
|
Fatty acid pattern of serum lecithin shows increased arachidonic acid and decreased linoleic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850461&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850461</a>]</span><br />
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|
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</span>
|
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
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|
|
- Variable age at onset<br /> -
|
|
Variable severity, correlates with age at onset<br /> -
|
|
Infantile, late-infantile, juvenile, and adult onset have been reported<br /> -
|
|
Patients with adult onset present with psychiatric features<br /> -
|
|
Common in populations of Finnish descent (incidence of 1:20 000, carrier frequency of 1 in 70)<br />
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|
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</span>
|
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
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|
|
- Caused by mutation in the palmitoyl-protein thioesterase 1 gene (PPT1, <a href="/entry/600722#0001">600722.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
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</div>
|
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</div>
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|
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
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<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Ceroid lipofuscinoses
|
|
- <a href="/phenotypicSeries/PS256730">PS256730</a>
|
|
- 15 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/484?start=-3&limit=10&highlight=484"> 1p34.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256730"> Ceroid lipofuscinosis, neuronal, 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256730"> 256730 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600722"> PPT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600722"> 600722 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/548?start=-3&limit=10&highlight=548"> 4q28.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610951"> Ceroid lipofuscinosis, neuronal, 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610951"> 610951 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611124"> MFSD8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611124"> 611124 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/301?start=-3&limit=10&highlight=301"> 7q11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611726"> Epilepsy, progressive myoclonic 3, with or without intracellular inclusions </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">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611726"> 611726 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611725"> KCTD7 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611725"> 611725 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/8/9?start=-3&limit=10&highlight=9"> 8p23.3 </a>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/600143"> Ceroid lipofuscinosis, neuronal, 8 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
|
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/600143"> 600143 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/607837"> CLN8 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607837"> 607837 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/8/9?start=-3&limit=10&highlight=9"> 8p23.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/610003"> Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/610003"> 610003 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607837"> CLN8 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607837"> 607837 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/11/63?start=-3&limit=10&highlight=63"> 11p15.5 </a>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/610127"> Ceroid lipofuscinosis, neuronal, 10 </a>
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610127"> 610127 </a>
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/116840"> CTSD </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/116840"> 116840 </a>
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</span>
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<a href="/geneMap/11/136?start=-3&limit=10&highlight=136"> 11p15.4 </a>
|
|
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204500"> Ceroid lipofuscinosis, neuronal, 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204500"> 204500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607998"> TPP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607998"> 607998 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/641?start=-3&limit=10&highlight=641"> 11q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615362"> Ceroid lipofuscinosis, neuronal, 13 (Kufs type) </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615362"> 615362 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603539"> CTSF </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603539"> 603539 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/13/231?start=-3&limit=10&highlight=231"> 13q22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256731"> Ceroid lipofuscinosis, neuronal, 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256731"> 256731 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608102"> CLN5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608102"> 608102 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/15/326?start=-3&limit=10&highlight=326"> 15q23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601780"> Ceroid lipofuscinosis, neuronal, 6A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601780"> 601780 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606725"> CLN6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606725"> 606725 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/15/326?start=-3&limit=10&highlight=326"> 15q23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204300"> Ceroid lipofuscinosis, neuronal, 6B (Kufs type) </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204300"> 204300 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606725"> CLN6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606725"> 606725 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/16/301?start=-3&limit=10&highlight=301"> 16p12.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204200"> Ceroid lipofuscinosis, neuronal, 3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204200"> 204200 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607042"> CLN3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607042"> 607042 </a>
|
|
</span>
|
|
</td>
|
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</tr>
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/638?start=-3&limit=10&highlight=638"> 17q21.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614706"> Ceroid lipofuscinosis, neuronal, 11 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614706"> 614706 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138945"> GRN </a>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
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|
<a href="/entry/138945"> 138945 </a>
|
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</span>
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</td>
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</tr>
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/20/487?start=-3&limit=10&highlight=487"> 20q13.33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162350"> Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/162350"> 162350 </a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/611203"> DNAJC5 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
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|
<a href="/entry/611203"> 611203 </a>
|
|
</span>
|
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</td>
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</tr>
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
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|
Not Mapped
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609055"> Ceroid lipofuscinosis, neuronal, 9 </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">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609055"> 609055 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609055"> CLN9 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609055"> 609055 </a>
|
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</span>
|
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</td>
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</tr>
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</tbody>
|
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</table>
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</div>
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<div class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<div>
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<br />
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<p>A number sign (#) is used with this entry because neuronal ceroid lipofuscinosis-1 (CLN1) is caused by homozygous or compound heterozygous mutation in the gene encoding palmitoyl-protein thioesterase-1 (PPT1; <a href="/entry/600722">600722</a>) on chromosome 1p34.</p>
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<p>The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). The patterns most often observed in CLN2 and CLN3 are 'curvilinear' and 'fingerprint' profiles, respectively. CLN4, CLN5, CLN6, CLN7, and CLN8 show mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (<a href="#24" class="mim-tip-reference" title="Mole, S. E., Williams, R. E., Goebel, H. H. <strong>Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.</strong> Neurogenetics 6: 107-126, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965709</a>] [<a href="https://doi.org/10.1007/s10048-005-0218-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965709">Mole et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15965709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Zeman, W., Dyken, P. <strong>Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic familial idiocy.</strong> Pediatrics 44: 570-583, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5346636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5346636</a>]" pmid="5346636">Zeman and Dyken (1969)</a> referred to these conditions as the 'neuronal ceroid lipofuscinoses.' <a href="#5" class="mim-tip-reference" title="Goebel, H. H. <strong>The neuronal ceroid-lipofuscinoses.</strong> J. Child Neurol. 10: 424-437, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576551</a>] [<a href="https://doi.org/10.1177/088307389501000602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8576551">Goebel (1995)</a> provided a comprehensive review of the NCLs and noted that they are possibly the most common group of neurodegenerative diseases in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5346636+8576551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Mole, S. E., Williams, R. E., Goebel, H. H. <strong>Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.</strong> Neurogenetics 6: 107-126, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965709</a>] [<a href="https://doi.org/10.1007/s10048-005-0218-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965709">Mole et al. (2005)</a> provided a detailed clinical and genetic review of the neuronal ceroid lipofuscinoses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15965709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Neuronal Ceroid Lipofuscinosis</em></strong></p><p>
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See also CLN2 (<a href="/entry/204500">204500</a>), caused by mutation in the TPP1 gene (<a href="/entry/607998">607998</a>) on chromosome 11p15; CLN3 (<a href="/entry/204200">204200</a>), caused by mutation in the CLN3 gene (<a href="/entry/607042">607042</a>) on 16p12; CLN4 (<a href="/entry/162350">162350</a>), caused by mutation in the DNAJC5 gene (<a href="/entry/611203">611203</a>) on 20q13; CLN5 (<a href="/entry/256731">256731</a>), caused by mutation in the CLN5 gene (<a href="/entry/608102">608102</a>) on 13q22; CLN6A (<a href="/entry/601780">601780</a>) and CLN6B (<a href="/entry/204300">204300</a>), both caused by mutation in the CLN6 gene (<a href="/entry/606725">606725</a>) on 15q21; CLN7 (<a href="/entry/610951">610951</a>), caused by mutation in the MFSD8 gene (<a href="/entry/611124">611124</a>) on 4q28; CLN8 (<a href="/entry/600143">600143</a>) and the Northern epilepsy variant of CLN8 (<a href="/entry/610003">610003</a>), both caused by mutation in the CLN8 gene (<a href="/entry/607837">607837</a>) on 8p23; CLN10 (<a href="/entry/610127">610127</a>), caused by mutation in the CTSD gene (<a href="/entry/116840">116840</a>) on 11p15; CLN11 (<a href="/entry/614706">614706</a>), caused by mutation in the GRN gene (<a href="/entry/138945">138945</a>) on 17q21; CLN13 (<a href="/entry/615362">615362</a>), caused by mutation in the CTSF gene (<a href="/entry/603539">603539</a>) on 11q13; and CLN14 (<a href="/entry/611726">611726</a>), caused by mutation in the KCTD7 gene (<a href="/entry/611725">611725</a>) on 7q11.</p><p>CLN9 (<a href="/entry/609055">609055</a>) has not been molecularly characterized.</p><p>A disorder that was formerly designated neuronal ceroid lipofuscinosis-12 (CLN12) is now considered to be a variable form of Kufor-Rakeb syndrome (KRS; <a href="/entry/606693">606693</a>).</p>
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<p>The CLNs were originally classified broadly by age at onset: CLN1 as the infantile-onset form, or the infantile-onset Finnish form, having first been described in that population; CLN2 as the late infantile-onset form; CLN3 as the juvenile-onset form; and CLN4 as the adult-onset form. With the identification of molecular defects, however, the CLNs are now classified numerically according to the underlying gene defect. CLN1 refers to CLN caused by mutation in the PPT1 gene, regardless of the age at onset (<a href="#24" class="mim-tip-reference" title="Mole, S. E., Williams, R. E., Goebel, H. H. <strong>Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.</strong> Neurogenetics 6: 107-126, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965709</a>] [<a href="https://doi.org/10.1007/s10048-005-0218-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965709">Mole et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15965709" 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><strong><em>Classic Infantile-Onset CLN1</em></strong></p><p>
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<a href="#8" class="mim-tip-reference" title="Hagberg, B., Sourander, P., Svennerholm, L. <strong>Late infantile progressive encephalopathy with disturbed poly-unsaturated fat metabolism.</strong> Acta Paediat. Scand. 57: 495-499, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5706364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5706364</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1968.tb06968.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5706364">Hagberg et al. (1968)</a> described 'progressive encephalopathy' in a child of unrelated Finnish parents. The disorder was characterized by mental retardation, loss of speech, minor motor seizures, regression of motor development, and ataxia. Histologically, the brain showed total derangement of cortical cytoarchitecture, severe degeneration of white matter, and deposits of granular material suggesting free fatty acids and unsaturated fatty acids. Biochemical studies showed a disturbance of linoleic acid metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5706364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Santavuori, P., Haltia, M., Rapola, J., Raitta, C. <strong>Infantile type of so-called neuronal ceroid-lipofuscinosis. Part I. A clinical study of 15 patients.</strong> J. Neurol. Sci. 18: 257-267, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4698309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4698309</a>] [<a href="https://doi.org/10.1016/0022-510x(73)90075-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4698309">Santavuori et al. (1973)</a> and <a href="#10" class="mim-tip-reference" title="Haltia, M., Rapola, J., Santavuori, P., Keranen, A. <strong>Infantile type of so-called neuronal ceroid-lipofuscinosis--Part 2. Morphological and biochemical studies.</strong> J. Neurol. Sci. 18: 269-285, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4121459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4121459</a>] [<a href="https://doi.org/10.1016/0022-510x(73)90076-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4121459">Haltia et al. (1973)</a> characterized the distinctive clinical and morphologic features of infantile-onset CLN1, respectively. Morphologic findings included severe neuronal destruction with massive accumulations of phagocytes, often binucleated, and unusually hypertrophic fibrillary astrocytes in the cerebral cortex. The fatty acid pattern of serum lecithin showed an increase of arachidonic acid and corresponding decrease of linoleic acid. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4121459+4698309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Santavuori, P., Haltia, M., Rapola, J. <strong>Infantile type of so-called neuronal ceroid lipofuscinosis.</strong> Dev. Med. Child Neurol. 16: 644-653, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4371326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4371326</a>] [<a href="https://doi.org/10.1111/j.1469-8749.1974.tb04183.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4371326">Santavuori et al. (1974)</a> reported that infantile-onset CLN is clinically homogeneous in the Finnish population. After normal development, visual failure, speech and motor deterioration, and seizures appeared between the ages of 6 and 24 months. Most patients had no cortical activity demonstrable by EEG by age 3 years. At least 55 cases of the same abnormality were identified in Finland (<a href="#9" class="mim-tip-reference" title="Hagberg, B. <strong>Personal Communication.</strong> Gotteborg, Sweden 9/4/1974."None>Hagberg, 1974</a>). Age at onset ranged from 8 to 18 months with rapid psychomotor deterioration, ataxia, and muscular hypotonia. Other features included microcephaly and myoclonic jerks; convulsions were less common. Affected individuals were blind by age 2 years with optic atrophy and macular and retinal changes but no pigment aggregation. Both the ERG and the EEG showed early extinction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4371326" 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="#1" class="mim-tip-reference" title="Baumann, R. J., Markesbery, W. R. <strong>Santavuori disease: diagnosis by leukocyte ultrastructure.</strong> Neurology 32: 1277-1281, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6890163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6890163</a>] [<a href="https://doi.org/10.1212/wnl.32.11.1277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6890163">Baumann and Markesbery (1982)</a> stated that about 60 cases of 'Santavuori disease' had been reported. They described the first American cases: 3 cases in 2 unrelated families. A brother and sister were from Appalachian Kentucky. Features were early developmental deterioration, retinal blindness, microcephaly, and seizures. <a href="#1" class="mim-tip-reference" title="Baumann, R. J., Markesbery, W. R. <strong>Santavuori disease: diagnosis by leukocyte ultrastructure.</strong> Neurology 32: 1277-1281, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6890163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6890163</a>] [<a href="https://doi.org/10.1212/wnl.32.11.1277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6890163">Baumann and Markesbery (1982)</a> found characteristic inclusion material in circulating leukocytes. This material was electron microscopically identical to that in brain tissues and was apparently unique to Santavuori disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6890163" 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="Vanhanen, S.-L., Raininko, R., Autti, T., Santavuori, P. <strong>MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis: part 2: MRI findings in 21 patients.</strong> J. Child Neurol. 10: 444-450, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576553</a>] [<a href="https://doi.org/10.1177/088307389501000604" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8576553">Vanhanen et al. (1995)</a> reviewed the MRI appearance of the brain in 21 patients with infantile neuronal ceroid lipofuscinosis and compared them to 46 neurologically normal controls. MRI abnormalities were detectable before clinical symptoms and changed with the progression of the disease. In the early stage there was generalized cerebral atrophy, thalamic hypointensity to the white matter and to the basal ganglia, and thin periventricular high-signal rims from 13 months onward on T2-weighted images. They noted a pathognomonic appearance in patients older than 4 years of age, and found that the signal intensity of the gray matter on T2-weighted images was less than that of the white matter, or reverse of the normal appearance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8576553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Late Infantile- and Juvenile-Onset CLN1</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Becker, K., Goebel, H.-H., Svennerholm, L., Wendel, U., Bremer, H. J. <strong>Clinical, morphological, and biochemical investigations on a patient with an unusual form of neuronal ceroid-lipofuscinosis.</strong> Europ. J. Pediat. 132: 197-206, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/510322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">510322</a>] [<a href="https://doi.org/10.1007/BF00442436" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="510322">Becker et al. (1979)</a> described the child of a consanguineous German couple who developed onset of mental and visual disturbances at age 3 years, followed by ataxia and myoclonic jerks. The chemical changes were those of the infantile form, but the electron microscopy of muscle and skin and the clinical course were more consistent with classically described later-onset forms of CLN (e.g., CLN2 or CLN3). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=510322" 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="Philippart, M., Chugani, H. T., Bateman, J. B. <strong>New Spielmeyer-Vogt variant with granular inclusions and early brain atrophy.</strong> Am. J. Med. Genet. 57: 160-164, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668322</a>] [<a href="https://doi.org/10.1002/ajmg.1320570210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7668322">Philippart et al. (1995)</a> and <a href="#13" class="mim-tip-reference" title="Hofman, I. L., Taschner, P. E. M. <strong>Late onset juvenile neuronal ceroid-lipofuscinosis with granular osmiophilic deposits (GROD).</strong> Am. J. Med. Genet. 57: 165-167, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668323</a>] [<a href="https://doi.org/10.1002/ajmg.1320570211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7668323">Hofman and Taschner (1995)</a> described a variant of juvenile-onset CLN in which electron microscopy demonstrated intracellular fine granular osmiophilic deposits (GROD) characteristic of the infantile subtype. Curvilinear and fingerprint bodies, characteristic of other forms of CLN were not identified. Learning disabilities began between ages 6 and 10 years, but visual failure was delayed until age 10 to 14 years. Linkage analysis of 1 family excluded markers on chromosome 16p12 associated with CLN3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7668323+7668322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Mitchison, H. M., Hofmann, S. L., Becerra, C. H. R., Munroe, P. B., Lake, B. D., Crow, Y. J., Stephenson, J. B. P., Williams, R. E., Hofman, I. L., Taschner, P. E. M., Martin, J.-J., Philippart, M., Andermann, E., Andermann, F., Mole, S. E., Gardiner, R. M., O'Rawe, A. M. <strong>Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits.</strong> Hum. Molec. Genet. 7: 291-297, 1998. Note: Erratum: Hum. Molec. Genet. 7: 765 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425237</a>] [<a href="https://doi.org/10.1093/hmg/7.2.291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425237">Mitchison et al. (1998)</a> reported 11 patients with juvenile-onset of CLN with GROD, including those reported by <a href="#28" class="mim-tip-reference" title="Philippart, M., Chugani, H. T., Bateman, J. B. <strong>New Spielmeyer-Vogt variant with granular inclusions and early brain atrophy.</strong> Am. J. Med. Genet. 57: 160-164, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668322</a>] [<a href="https://doi.org/10.1002/ajmg.1320570210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7668322">Philippart et al. (1995)</a> and <a href="#13" class="mim-tip-reference" title="Hofman, I. L., Taschner, P. E. M. <strong>Late onset juvenile neuronal ceroid-lipofuscinosis with granular osmiophilic deposits (GROD).</strong> Am. J. Med. Genet. 57: 165-167, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668323</a>] [<a href="https://doi.org/10.1002/ajmg.1320570211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7668323">Hofman and Taschner (1995)</a>. Deterioration of intellect began between ages 7 and 13 years, deterioration of motor function between ages 7 and 15 years, deterioration of vision between ages 6 and 14 years, and onset of EEG changes and epilepsy between ages 7 and 17 years. Vacuolated lymphocytes were not detected in 11 of 16 patients. The tissues in which granular osmiophilic deposits were observed included skin, conjunctiva, rectum, and blood. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7668323+9425237+7668322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Wisniewski, K. E., Connell, F., Kaczmarski, W., Kaczmarski, A., Siakotos, A., Becerra, C. R., Hofmann, S. L. <strong>Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL.</strong> Pediat. Neurol. 18: 119-123, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9535296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9535296</a>] [<a href="https://doi.org/10.1016/s0887-8994(97)00173-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9535296">Wisniewski et al. (1998)</a> reported 5 patients from 3 unrelated families with late infantile-onset CLN1 with GROD. PPT1 activity was less than 10% of normal values, suggesting a variant form of CLN1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9535296" 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="#3" class="mim-tip-reference" title="Das, A. K., Becerra, C. H. R., Yi, W., Lu, J.-Y., Siakotos, A. N., Wisniewski, K. E., Hofmann, S. L. <strong>Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S.</strong> J. Clin. Invest. 102: 361-370, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9664077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9664077</a>] [<a href="https://doi.org/10.1172/JCI3112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9664077">Das et al. (1998)</a> found excellent correlation between absence of PPT1 activity and GROD histology among 32 unrelated individuals with CLN. All 23 patients with pure GROD and 6 (67%) of 9 patients with GROD mixed with curvilinear or fingerprint inclusions had decreased PPT1 activity. Fourteen patients had infantile onset before 24 months of age, 5 had late-infantile onset between ages 2 and 4, and 13 had juvenile onset after age 5 years. The 3 patients with normal PPT1 activity all had juvenile-onset CLN; 1 of these patients was subsequently found to have mutations in the CLN3 gene (<a href="/entry/607042">607042</a>). Twenty-eight patients with CLN without GROD histology all had normal PPT1 activity. The patients included the 3 probands reported by <a href="#38" class="mim-tip-reference" title="Wisniewski, K. E., Connell, F., Kaczmarski, W., Kaczmarski, A., Siakotos, A., Becerra, C. R., Hofmann, S. L. <strong>Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL.</strong> Pediat. Neurol. 18: 119-123, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9535296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9535296</a>] [<a href="https://doi.org/10.1016/s0887-8994(97)00173-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9535296">Wisniewski et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9664077+9535296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Adult-Onset CLN1</em></strong></p><p>
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<a href="#34" class="mim-tip-reference" title="van Diggelen, O. P., Thobois, S., Tilikete, C., Zabot, M.-T., Keulemans, J. L. M., van Bunderen, P. A., Taschner, P. E. M., Losekoot, M., Voznyi, Y. V. <strong>Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease.</strong> Ann. Neurol. 50: 269-272, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11506414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11506414</a>] [<a href="https://doi.org/10.1002/ana.1103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11506414">Van Diggelen et al. (2001)</a> reported 2 sisters with adult-onset neuronal CLN1 confirmed by the finding of compound heterozygous mutations in the PPT1 gene (<a href="/entry/600722#0006">600722.0006</a>; <a href="/entry/600722#0009">600722.0009</a>). Onset in both patients was in the thirties, with symptoms of depression progressing to cognitive decline, cerebellar ataxia, parkinsonism, and decreased verbal fluency in their fifties. Both patients showed generalized brain atrophy on MRI. Enzyme analysis showed severe PPT deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11506414" 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="#29" class="mim-tip-reference" title="Ramadan, H., Al-Din, A. S., Ismail, A., Balen, F., Varma, A., Twomey, A., Watts, R., Jackson, M., Anderson, G., Green, E., Mole, S. E. <strong>Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1.</strong> Neurology 68: 387-388, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17261688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17261688</a>] [<a href="https://doi.org/10.1212/01.wnl.0000252825.85947.2f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17261688">Ramadan et al. (2007)</a> reported a 24-year-old woman who presented with psychiatric features, including low mood, irritability, lack of interest, bizarre behavior, and academic decline. She deteriorated over the next 18 months, developing tunnel vision, retinitis pigmentosa, visual hallucinations, and further cognitive decline. Brain MRI showed marked generalized cerebral and cerebellar atrophy. Skin and rectal mucosal biopsies showed a storage disease with autofluorescent granular osmiophilic deposits, and biochemical studies showed decreased PPT1 activity. Genetic analysis identified compound heterozygosity for 2 mutations in the PPT1 gene (<a href="/entry/600722#0006">600722.0006</a>; <a href="/entry/600722#0010">600722.0010</a>). <a href="#29" class="mim-tip-reference" title="Ramadan, H., Al-Din, A. S., Ismail, A., Balen, F., Varma, A., Twomey, A., Watts, R., Jackson, M., Anderson, G., Green, E., Mole, S. E. <strong>Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1.</strong> Neurology 68: 387-388, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17261688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17261688</a>] [<a href="https://doi.org/10.1212/01.wnl.0000252825.85947.2f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17261688">Ramadan et al. (2007)</a> emphasized the late onset in this patient and noted the similarities to the sisters reported by <a href="#34" class="mim-tip-reference" title="van Diggelen, O. P., Thobois, S., Tilikete, C., Zabot, M.-T., Keulemans, J. L. M., van Bunderen, P. A., Taschner, P. E. M., Losekoot, M., Voznyi, Y. V. <strong>Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease.</strong> Ann. Neurol. 50: 269-272, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11506414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11506414</a>] [<a href="https://doi.org/10.1002/ana.1103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11506414">Van Diggelen et al. (2001)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17261688+11506414" 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>By linkage analysis in Finnish families with infantile-onset CLN1, <a href="#17" class="mim-tip-reference" title="Jokiaho, I., Puhakka, L., Santavuori, P., Manninen, T., Nyman, K., Peltonen, L. <strong>Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses.</strong> Genomics 8: 391-393, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2249855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2249855</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90298-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2249855">Jokiaho et al. (1990)</a> excluded linkage to chromosome 16, where the gene for Batten disease (CLN3) had been mapped. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2249855" 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 studies of 15 Finnish families with infantile-onset CLN1, <a href="#15" class="mim-tip-reference" title="Jarvela, I., Schleutker, J., Haataja, L., Santavuori, P., Puhakka, L., Manninen, T., Palotie, A., Sandkuijl, L. A., Renlund, M., White, R., Aula, P., Peltonen, L. <strong>Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1.</strong> Genomics 9: 170-173, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672288</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90235-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1672288">Jarvela et al. (1991)</a> demonstrated linkage to chromosome 1p (maximum lod scores of 3.38 for D1S57, 3.56 for D1S7, and 3.56 for D1S79). <a href="#16" class="mim-tip-reference" title="Jarvela, I. <strong>Infantile neuronal ceroid lipofuscinosis (CLN1): linkage disequilibrium in the Finnish population and evidence that variant late infantile form (variant CLN2) represents a nonallelic locus.</strong> Genomics 10: 333-337, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2071142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2071142</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90316-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2071142">Jarvela (1991)</a> presented a map of the birthplaces of great-grandparents of 35 patients with CLN1. The wide distribution of this ancestry suggested a very old founder effect. On the basis of further linkage studies, <a href="#14" class="mim-tip-reference" title="Jarvela, I., Santavuori, P., Vesa, J., Rapola, J., Palotie, A., Peltonen, L. <strong>Assignment of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) to the short arm of chromosome 1 (Abstract)</strong> Cytogenet. Cell Genet. 58: 1856-1857, 1991."None>Jarvela et al. (1991)</a> mapped the CLN1 gene to chromosome 1p32. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1672288+2071142" 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="Hellsten, E., Vesa, J., Speer, M. C., Makela, T. P., Jarvela, I., Alitalo, K., Ott, J., Peltonen, L. <strong>Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: incorporation of linkage disequilibrium in multipoint analysis.</strong> Genomics 16: 720-725, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8325646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8325646</a>] [<a href="https://doi.org/10.1006/geno.1993.1253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8325646">Hellsten et al. (1993)</a> observed linkage disequilibrium between CLN1 and a newly discovered, highly polymorphic marker. Incorporation of the observed linkage disequilibrium into multipoint linkage analysis significantly increased the informativeness of the limited family material and facilitated refined assignment of the CLN1 locus. <a href="#11" class="mim-tip-reference" title="Hellsten, E., Vesa, J., Heiskanen, M., Makela, T. P., Jarvela, I., Cowell, J. K., Mead, S., Alitalo, K., Palotie, A., Peltonen, L. <strong>Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus.</strong> Genomics 25: 404-412, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789974</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80040-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789974">Hellsten et al. (1995)</a> constructed a pulsed field gel electrophoresis (PFGE) map of 4 Mb in the region of the CLN1 gene. They established the order of several loci at 1p32 by combining data obtained from analysis of a chromosome 1 somatic cell hybrid panel, PFGE, and interphase fluorescence in situ hybridization. They found that a 1-Mb contig contained MYCL1, the HY-TM1 marker closely linked to CLN1, RLF (<a href="/entry/180610">180610</a>), and COL9A2 (<a href="/entry/120260">120260</a>). Within the contig, they identified 5 CpG islands, in addition to those associated with the earlier cloned genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7789974+8325646" 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="#37" class="mim-tip-reference" title="Voznyi, Y. V., Keulemans, J. L. M., Mancini, G. M. S., Catsman-Berrevoets, C. E., Young, E., Winchester, B., Kleijer, W. J., van Diggelen, O. P. <strong>A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants.</strong> J. Med. Genet. 36: 471-474, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10874636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10874636</a>]" pmid="10874636">Voznyi et al. (1999)</a> reported a new fluorimetric assay for PPT activity based on the fluorochrome 4-methylumbelliferone. PPT1 activity was detectable in fibroblasts, leukocytes, lymphoblasts, amniotic fluid cells, and chorionic villi, but was deficient in tissues from CLN1 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10874636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="de Vries, B. B. A., Kleijer, W. J., Keulemans, J. L. M., Voznyi, Y. V., Franken, P. F., Eurlings, M. C. M., Galjaard, R. J., Losekoot, M., Catsman-Berrevoets, C. E., Breuning, M. H., Taschner, P. E. M., van Diggelen, O. P. <strong>First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay and CLN1 mutation analysis.</strong> Prenatal Diag. 19: 559-562, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10416973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10416973</a>]" pmid="10416973">De Vries et al. (1999)</a> reported prenatal diagnosis of CLN1 by chorionic villi sampling. PPT1 activity was deficient and molecular analysis identified a homozygous mutation in the PPT1 gene (<a href="/entry/600722#0008">600722.0008</a>). The pregnancy was terminated and the PPT deficiency was confirmed in cultured chorionic villi cells as well as in cultured fetal skin fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10416973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of CLN1 in the Finnish families reported by <a href="#36" class="mim-tip-reference" title="Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S.L., Peltonen, L. <strong>Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis.</strong> Nature 376: 584-588, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7637805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7637805</a>] [<a href="https://doi.org/10.1038/376584a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7637805">Vesa et al. (1995)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7637805" 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>By positional candidate gene methods, <a href="#36" class="mim-tip-reference" title="Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S.L., Peltonen, L. <strong>Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis.</strong> Nature 376: 584-588, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7637805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7637805</a>] [<a href="https://doi.org/10.1038/376584a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7637805">Vesa et al. (1995)</a> identified a homozygous mutation (R122W; <a href="/entry/600722#0001">600722.0001</a>) in the PPT1 gene in patients with infantile-onset CLN1 from 40 of 42 Finnish families. The findings were consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7637805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Mitchison, H. M., Hofmann, S. L., Becerra, C. H. R., Munroe, P. B., Lake, B. D., Crow, Y. J., Stephenson, J. B. P., Williams, R. E., Hofman, I. L., Taschner, P. E. M., Martin, J.-J., Philippart, M., Andermann, E., Andermann, F., Mole, S. E., Gardiner, R. M., O'Rawe, A. M. <strong>Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits.</strong> Hum. Molec. Genet. 7: 291-297, 1998. Note: Erratum: Hum. Molec. Genet. 7: 765 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425237</a>] [<a href="https://doi.org/10.1093/hmg/7.2.291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425237">Mitchison et al. (1998)</a> identified homozygosity or compound heterozygosity for mutations in the PPT1 gene (<a href="/entry/600722#0002">600722.0002</a>-<a href="/entry/600722#0006">600722.0006</a>) in 11 patients with juvenile-onset CLN1 with the ultrastructural findings of granular osmiophilic deposits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425237" 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="#3" class="mim-tip-reference" title="Das, A. K., Becerra, C. H. R., Yi, W., Lu, J.-Y., Siakotos, A. N., Wisniewski, K. E., Hofmann, S. L. <strong>Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S.</strong> J. Clin. Invest. 102: 361-370, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9664077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9664077</a>] [<a href="https://doi.org/10.1172/JCI3112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9664077">Das et al. (1998)</a> identified 19 different mutations in the PPT1 gene in 57 of 58 mutated alleles from 29 patient-derived cell lines. The R151X mutation (<a href="/entry/600722#0006">600722.0006</a>) accounted for 40% of the alleles, and the T75P mutation (<a href="/entry/600722#0002">600722.0002</a>) accounted for 13% of the alleles. Fifty percent of patients had infantile onset, 17% had late-infantile onset, and 33% had juvenile onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9664077" 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="#19" class="mim-tip-reference" title="Kim, S.-J., Zhang, Z., Lee, Y.-C., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.</strong> Hum. Molec. Genet. 15: 1580-1586, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16571600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16571600</a>] [<a href="https://doi.org/10.1093/hmg/ddl078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16571600">Kim et al. (2006)</a> noted that apoptosis is 1 of the major causes of neurodegeneration in INCL. In a follow-up to studies in a mouse model of CLN1 that showed activation of the endoplasmic reticulum stress response (<a href="#40" class="mim-tip-reference" title="Zhang, Z., Lee, Y.-C., Kim, S.-J., Choi, M. S., Tsai, P.-C., Xu, Y., Xiao, Y.-J., Zhang, P., Heffer, A., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.</strong> Hum. Molec. Genet. 15: 337-346, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16368712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16368712</a>] [<a href="https://doi.org/10.1093/hmg/ddi451" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16368712">Zhang et al., 2006</a>), <a href="#19" class="mim-tip-reference" title="Kim, S.-J., Zhang, Z., Lee, Y.-C., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.</strong> Hum. Molec. Genet. 15: 1580-1586, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16571600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16571600</a>] [<a href="https://doi.org/10.1093/hmg/ddl078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16571600">Kim et al. (2006)</a> studied signals of apoptosis in brain samples from a patient with CLN1. Brain tissue showed increased levels of mitochondrial superoxide dismutase-2 (SOD2; <a href="/entry/147460">147460</a>), caspase-9 (CASP9; <a href="/entry/602234">602234</a>), caspase-3 (CASP3; <a href="/entry/600636">600636</a>), and cleaved PARP1 (<a href="/entry/173870">173870</a>) compared to control brain samples. These findings were consistent with rapid neuronal death by apoptosis. Studies of Ppt1-null mice revealed similar patterns, and studies of cultured neurospheres indicated that ER stress caused elevated levels of reactive oxygen species (ROS). <a href="#19" class="mim-tip-reference" title="Kim, S.-J., Zhang, Z., Lee, Y.-C., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.</strong> Hum. Molec. Genet. 15: 1580-1586, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16571600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16571600</a>] [<a href="https://doi.org/10.1093/hmg/ddl078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16571600">Kim et al. (2006)</a> proposed that the rapid progression of neurodegeneration in human INCL is likely to be caused by ER stress-mediated caspase-12 (CASP12; <a href="/entry/608633">608633</a>) activation as well as by elevated ROS production, which stimulates SOD2 production and destabilization of calcium homeostasis. Together these abnormalities mediate activation of CASP9, CASP3, and cleavage of PARP, which is indicative of apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16368712+16571600" 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>CLN1 is most common in populations of Finnish descent, with an incidence of 1:20,000 and a carrier frequency of 1 in 70 (summary by <a href="#22" class="mim-tip-reference" title="Miller, J. N., Kovacs, A. D., Pearce, D. A. <strong>The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.</strong> Hum. Molec. Genet. 24: 185-196, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25205113[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddu428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205113">Miller et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205113" 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="Gupta, P., Soyombo, A. A., Atashband, A., Wisniewski, K. E., Shelton, J. M., Richardson, J. A., Hammer, R. E., Hofmann, S. L. <strong>Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice.</strong> Proc. Nat. Acad. Sci. 98: 13566-13571, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11717424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11717424</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11717424[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.251485198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11717424">Gupta et al. (2001)</a> engineered disruptions in the Ppt1 and Ppt2 (<a href="/entry/603298">603298</a>) genes to create knockout mice that were deficient in either enzyme. Both lines of mice were viable and fertile; however, both lines developed spasticity (a 'clasping' phenotype) at a median age of 21 weeks and 29 weeks, respectively. Motor abnormalities progressed in the Ppt1 knockout mice, leading to death by 10 months of age. In contrast, most Ppt2 mice were alive at 12 months. Myoclonic jerking and seizures were prominent in the Ppt1 mice. Autofluorescent storage material was striking throughout the brains of both strains of mice. Neuronal loss and apoptosis were particularly prominent in Ppt1-deficient brains. These studies provided a mouse model for infantile neuronal ceroid lipofuscinosis and further suggested that PPT2 serves a role in the brain that is not carried out by PPT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11717424" 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="#40" class="mim-tip-reference" title="Zhang, Z., Lee, Y.-C., Kim, S.-J., Choi, M. S., Tsai, P.-C., Xu, Y., Xiao, Y.-J., Zhang, P., Heffer, A., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.</strong> Hum. Molec. Genet. 15: 337-346, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16368712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16368712</a>] [<a href="https://doi.org/10.1093/hmg/ddi451" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16368712">Zhang et al. (2006)</a> reported that the brains of Ppt1-null mice accumulated autofluorescent material, abnormalities of the neuronal endoplasmic reticulum (ER), and showed progressive neuronal apoptosis that correlated with neurologic motor impairment. There was an abnormal accumulation of palmitoylated GAP43 (<a href="/entry/162060">162060</a>) in the ER. Increased levels of this and other S-acylated proteins coincided with activation of the unfolded protein response, characterized by increased phosphorylation of EIF2A (<a href="/entry/609234">609234</a>) and activation of CASP12, which ultimately leads to cellular apoptosis. <a href="#40" class="mim-tip-reference" title="Zhang, Z., Lee, Y.-C., Kim, S.-J., Choi, M. S., Tsai, P.-C., Xu, Y., Xiao, Y.-J., Zhang, P., Heffer, A., Mukherjee, A. B. <strong>Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.</strong> Hum. Molec. Genet. 15: 337-346, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16368712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16368712</a>] [<a href="https://doi.org/10.1093/hmg/ddi451" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16368712">Zhang et al. (2006)</a> concluded that PPT1 deficiency leads to neurodegeneration by activation of the unfolded protein response as a result of abnormal accumulation of palmitoylated proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16368712" 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>Neural communication relies on repeated cycles of exo- and endocytosis of synaptic vesicles containing neurotransmitters at the plasma membranes of nerve terminals. In the mouse brain, <a href="#20" class="mim-tip-reference" title="Kim, S.-J., Zhang, Z., Sarkar, C., Tsai, P.-C., Lee, Y.-C., Dye, L., Mukherjkee, A. B. <strong>Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice.</strong> J. Clin. Invest. 118: 3075-3086, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18704195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18704195</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18704195[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI33482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18704195">Kim et al. (2008)</a> found that Ppt1 localized in the synaptosomes and synaptic vesicles of the presynaptic compartment under physiologic conditions. Ppt1 deficiency resulted in abnormal and persistent membrane retention of palmitoylated synaptic vesicle-associated proteins, including VAMP2 (<a href="/entry/185881">185881</a>), SNAP25 (<a href="/entry/600322">600322</a>), syntaxin-1 (STX1A; <a href="/entry/186590">186590</a>), SYTI (<a href="/entry/185605">185605</a>), and GAD65 (<a href="/entry/138275">138275</a>) in brain tissue from both human patients with neuronal lipofuscinosis and Ppt1-deficient mice. Since these S-acylated proteins must undergo depalmitoylation to detach from the membrane, which is required for recycling, Ppt1 deficiency may cause these proteins to remain membrane bound. <a href="#20" class="mim-tip-reference" title="Kim, S.-J., Zhang, Z., Sarkar, C., Tsai, P.-C., Lee, Y.-C., Dye, L., Mukherjkee, A. B. <strong>Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice.</strong> J. Clin. Invest. 118: 3075-3086, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18704195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18704195</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18704195[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI33482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18704195">Kim et al. (2008)</a> proposed a mechanism by which PPT1 deficiency leads to the disruption of synaptic vesicle recycling, prevents the regeneration of fresh vesicles, and results in a progressive decline in the total pool size, which ultimately impairs neurotransmission. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18704195" 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="#22" class="mim-tip-reference" title="Miller, J. N., Kovacs, A. D., Pearce, D. A. <strong>The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.</strong> Hum. Molec. Genet. 24: 185-196, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25205113[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddu428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205113">Miller et al. (2015)</a> generated a transgenic mouse model homozygous for the common R151X PPT1 mutation (<a href="/entry/600722#0006">600722.0006</a>). The phenotype of the mutant mice recapitulated that observed in humans, including impaired motor function, decreased exploratory behavior, accumulation of autofluorescent material in the brain, and widespread astrogliosis and microglial activation throughout the brain. PPT1 enzyme activity in homozygous mice was 1.7 to 3.1% of controls. Administration of the read-through compound ataluren (PTC124) increased PPT1 enzyme activity and protein level in mutant mice in a proof-of-principle study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205113" 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="#27" class="mim-tip-reference" title="Oppenheimer, E. H., Andrews, E. C., Jr. <strong>Ceroid storage disease in childhood.</strong> Pediatrics 23: 1091-1102, 1959.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13657591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13657591</a>]" pmid="13657591">Oppenheimer and Andrews (1959)</a> reported 2 patients with 'ceroid storage disease': a 4-year-old white male from West Virginia who died from liver failure and had ceroid deposits of liver, spleen and intestinal mucosa, and a white 22-month-old female who at autopsy had ceroid limited largely to hepatic macrophages. The sister and 2 brothers reported by <a href="#26" class="mim-tip-reference" title="Nelson, P., Santamaria, A., Olson, R. L., Nayak, N. C. <strong>Generalized lymphohistiocytic infiltration: a familial disease not previously described and different from Letterer-Siwe disease and Chediak-Higashi syndrome.</strong> Pediatrics 27: 931-950, 1961.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13728304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13728304</a>]" pmid="13728304">Nelson et al. (1961)</a> may have had the same condition. The isolated case reported by <a href="#18" class="mim-tip-reference" title="Jonas, O. <strong>Ceroid storage in a child with a Niemann-Pick type syndrome.</strong> Med. J. Aust. 2: 551-554, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5922340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5922340</a>] [<a href="https://doi.org/10.5694/j.1326-5377.1966.tb97330.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5922340">Jonas (1966)</a> may have had the same or a related condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13657591+13728304+5922340" 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="Ryan, G. B., Anderson, R. M., Menkes, J. H., Dennett, X. <strong>Lipofuscin (ceroid) storage disease of the brain: neuropathological and neurochemical studies.</strong> Brain 93: 617-628, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5507017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5507017</a>] [<a href="https://doi.org/10.1093/brain/93.3.617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5507017">Ryan et al. (1970)</a> provided a detailed report of a boy with 'lipofuscin storage disease.' <a href="#21" class="mim-tip-reference" title="Menkes, J. H. <strong>Personal Communication.</strong> Beverly Hills, Calif. 2/26/1982."None>Menkes (1982)</a> reviewed this paper and suggested, mainly on clinical grounds because the electron microscopy was unsatisfactory, that the correct diagnosis was the Finnish or Santavuori type of infantile neuronal ceroid lipofuscinosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5507017" 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 href="#Hagberg1974" class="mim-tip-reference" title="Hagberg, B. <strong>Personal Communication.</strong> Gotteborg, Sweden 9/4/1974.">Hagberg et al. (1974)</a>; <a href="#Mole1999" class="mim-tip-reference" title="Mole, S. E. <strong>Batten's disease: eight genes and still counting? (Commentary)</strong> Lancet 354: 443-445, 1999.">Mole (1999)</a>; <a href="#Santavuori1980" class="mim-tip-reference" title="Santavuori, P. <strong>Infantile type of neuronal ceroid-lipofuscinosis (INCL). In: Eriksson, A. W.; Forsius, H. R.; Nevanlinna, H. R.; Workman, P. L.; Norio, R. K.: Population Structure and Genetic Disorders.</strong> New York: Academic Press (pub.) 1980. Pp. 626-632.">Santavuori (1980)</a>
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Baumann, R. J., Markesbery, W. R.
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<strong>Santavuori disease: diagnosis by leukocyte ultrastructure.</strong>
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Neurology 32: 1277-1281, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6890163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6890163</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6890163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.32.11.1277" target="_blank">Full Text</a>]
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Becker, K., Goebel, H.-H., Svennerholm, L., Wendel, U., Bremer, H. J.
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<strong>Clinical, morphological, and biochemical investigations on a patient with an unusual form of neuronal ceroid-lipofuscinosis.</strong>
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Europ. J. Pediat. 132: 197-206, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/510322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">510322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=510322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00442436" target="_blank">Full Text</a>]
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Das, A. K., Becerra, C. H. R., Yi, W., Lu, J.-Y., Siakotos, A. N., Wisniewski, K. E., Hofmann, S. L.
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<strong>Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S.</strong>
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J. Clin. Invest. 102: 361-370, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9664077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9664077</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9664077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI3112" target="_blank">Full Text</a>]
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de Vries, B. B. A., Kleijer, W. J., Keulemans, J. L. M., Voznyi, Y. V., Franken, P. F., Eurlings, M. C. M., Galjaard, R. J., Losekoot, M., Catsman-Berrevoets, C. E., Breuning, M. H., Taschner, P. E. M., van Diggelen, O. P.
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<strong>First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay and CLN1 mutation analysis.</strong>
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Prenatal Diag. 19: 559-562, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10416973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10416973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10416973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Goebel, H. H.
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<strong>The neuronal ceroid-lipofuscinoses.</strong>
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J. Child Neurol. 10: 424-437, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8576551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1177/088307389501000602" target="_blank">Full Text</a>]
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Gupta, P., Soyombo, A. A., Atashband, A., Wisniewski, K. E., Shelton, J. M., Richardson, J. A., Hammer, R. E., Hofmann, S. L.
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<strong>Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice.</strong>
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Proc. Nat. Acad. Sci. 98: 13566-13571, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11717424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11717424</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11717424[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11717424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.251485198" target="_blank">Full Text</a>]
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Hagberg, B., Haltia, M., Sourander, P., Svennerholm, L., Eeg-Olofsson, O.
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<strong>Polyunsaturated fatty acid lipidosis infantile form of so-called neuronal ceroid lipofuscinosis. I. Clinical and morphological aspects.</strong>
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Acta Paediat. Scand. 63: 753-763, 1974.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4415126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4415126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4415126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1651-2227.1974.tb17001.x" target="_blank">Full Text</a>]
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Hagberg, B., Sourander, P., Svennerholm, L.
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<strong>Late infantile progressive encephalopathy with disturbed poly-unsaturated fat metabolism.</strong>
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Acta Paediat. Scand. 57: 495-499, 1968.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5706364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5706364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5706364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1651-2227.1968.tb06968.x" target="_blank">Full Text</a>]
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<strong>Personal Communication.</strong>
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Gotteborg, Sweden 9/4/1974.
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Haltia, M., Rapola, J., Santavuori, P., Keranen, A.
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<strong>Infantile type of so-called neuronal ceroid-lipofuscinosis--Part 2. Morphological and biochemical studies.</strong>
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J. Neurol. Sci. 18: 269-285, 1973.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4121459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4121459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4121459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0022-510x(73)90076-2" target="_blank">Full Text</a>]
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Hellsten, E., Vesa, J., Heiskanen, M., Makela, T. P., Jarvela, I., Cowell, J. K., Mead, S., Alitalo, K., Palotie, A., Peltonen, L.
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[<a href="https://doi.org/10.1016/0888-7543(95)80040-s" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1993.1253" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320570211" target="_blank">Full Text</a>]
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<strong>Assignment of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) to the short arm of chromosome 1 (Abstract)</strong>
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<strong>Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1.</strong>
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[<a href="https://doi.org/10.1016/0888-7543(91)90235-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(91)90316-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90298-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl078" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddu428" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/7.2.291" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10048-005-0218-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320570210" target="_blank">Full Text</a>]
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Ramadan, H., Al-Din, A. S., Ismail, A., Balen, F., Varma, A., Twomey, A., Watts, R., Jackson, M., Anderson, G., Green, E., Mole, S. E.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17261688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17261688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17261688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000252825.85947.2f" target="_blank">Full Text</a>]
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<a id="Ryan1970" class="mim-anchor"></a>
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Ryan, G. B., Anderson, R. M., Menkes, J. H., Dennett, X.
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<strong>Lipofuscin (ceroid) storage disease of the brain: neuropathological and neurochemical studies.</strong>
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[<a href="https://doi.org/10.1093/brain/93.3.617" target="_blank">Full Text</a>]
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Santavuori, P., Haltia, M., Rapola, J., Raitta, C.
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<strong>Infantile type of so-called neuronal ceroid-lipofuscinosis. Part I. A clinical study of 15 patients.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4698309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4698309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4698309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0022-510x(73)90075-0" target="_blank">Full Text</a>]
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Santavuori, P., Haltia, M., Rapola, J.
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<strong>Infantile type of so-called neuronal ceroid lipofuscinosis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4371326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4371326</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4371326" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1469-8749.1974.tb04183.x" target="_blank">Full Text</a>]
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Santavuori, P.
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<strong>Infantile type of neuronal ceroid-lipofuscinosis (INCL). In: Eriksson, A. W.; Forsius, H. R.; Nevanlinna, H. R.; Workman, P. L.; Norio, R. K.: Population Structure and Genetic Disorders.</strong>
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van Diggelen, O. P., Thobois, S., Tilikete, C., Zabot, M.-T., Keulemans, J. L. M., van Bunderen, P. A., Taschner, P. E. M., Losekoot, M., Voznyi, Y. V.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11506414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11506414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11506414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.1103" target="_blank">Full Text</a>]
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Vanhanen, S.-L., Raininko, R., Autti, T., Santavuori, P.
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<strong>MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis: part 2: MRI findings in 21 patients.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8576553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1177/088307389501000604" target="_blank">Full Text</a>]
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Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S.L., Peltonen, L.
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<strong>Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis.</strong>
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Nature 376: 584-588, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7637805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7637805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7637805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/376584a0" target="_blank">Full Text</a>]
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Voznyi, Y. V., Keulemans, J. L. M., Mancini, G. M. S., Catsman-Berrevoets, C. E., Young, E., Winchester, B., Kleijer, W. J., van Diggelen, O. P.
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<strong>A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants.</strong>
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J. Med. Genet. 36: 471-474, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10874636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10874636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10874636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Wisniewski, K. E., Connell, F., Kaczmarski, W., Kaczmarski, A., Siakotos, A., Becerra, C. R., Hofmann, S. L.
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<strong>Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL.</strong>
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Pediat. Neurol. 18: 119-123, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9535296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9535296</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9535296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0887-8994(97)00173-2" target="_blank">Full Text</a>]
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Zeman, W., Dyken, P.
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<strong>Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic familial idiocy.</strong>
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Pediatrics 44: 570-583, 1969.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5346636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5346636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5346636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Zhang, Z., Lee, Y.-C., Kim, S.-J., Choi, M. S., Tsai, P.-C., Xu, Y., Xiao, Y.-J., Zhang, P., Heffer, A., Mukherjee, A. B.
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<strong>Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.</strong>
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Hum. Molec. Genet. 15: 337-346, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16368712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16368712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16368712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi451" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 10/20/2015
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Cassandra L. Kniffin - updated : 8/16/2010<br>Cassandra L. Kniffin - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 11/24/2008<br>Cassandra L. Kniffin - updated : 2/4/2008<br>Cassandra L. Kniffin - reorganized : 3/24/2006<br>Cassandra L. Kniffin - updated : 3/16/2006<br>Victor A. McKusick - updated : 10/28/1999<br>Victor A. McKusick - updated : 9/8/1999<br>Michael J. Wright - updated : 6/18/1999<br>Orest Hurko - updated : 3/9/1996
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Victor A. McKusick : 6/4/1986
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carol : 09/03/2024
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carol : 08/30/2024<br>carol : 12/01/2021<br>carol : 02/25/2021<br>carol : 03/06/2018<br>ckniffin : 11/23/2016<br>alopez : 09/16/2016<br>carol : 05/18/2016<br>alopez : 12/4/2015<br>ckniffin : 10/20/2015<br>carol : 9/16/2015<br>ckniffin : 10/9/2013<br>carol : 8/14/2013<br>ckniffin : 8/8/2013<br>carol : 11/28/2012<br>carol : 8/2/2012<br>ckniffin : 7/31/2012<br>alopez : 7/13/2012<br>ckniffin : 7/9/2012<br>ckniffin : 9/15/2011<br>wwang : 5/17/2011<br>ckniffin : 5/16/2011<br>wwang : 8/24/2010<br>ckniffin : 8/16/2010<br>wwang : 11/5/2009<br>ckniffin : 10/30/2009<br>wwang : 11/24/2008<br>wwang : 2/19/2008<br>ckniffin : 2/4/2008<br>alopez : 6/20/2007<br>wwang : 7/31/2006<br>ckniffin : 7/14/2006<br>ckniffin : 3/27/2006<br>carol : 3/24/2006<br>ckniffin : 3/21/2006<br>carol : 3/20/2006<br>ckniffin : 3/20/2006<br>ckniffin : 3/16/2006<br>carol : 11/18/2004<br>ckniffin : 7/30/2003<br>carol : 7/9/2003<br>carol : 7/9/2003<br>ckniffin : 6/23/2003<br>carol : 2/22/2002<br>mgross : 10/28/1999<br>carol : 10/14/1999<br>terry : 9/8/1999<br>mgross : 7/7/1999<br>mgross : 7/7/1999<br>terry : 6/18/1999<br>terry : 6/9/1999<br>dkim : 7/23/1998<br>dkim : 7/23/1998<br>terry : 4/15/1996<br>mark : 3/9/1996<br>terry : 3/1/1996<br>mark : 12/6/1995<br>mark : 11/8/1995<br>carol : 3/6/1995<br>davew : 8/17/1994<br>warfield : 4/19/1994<br>mimadm : 3/11/1994<br>carol : 6/18/1993
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<strong>#</strong> 256730
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CEROID LIPOFUSCINOSIS, NEURONAL, 1; CLN1
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<span class="mim-font">
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CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET
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<span class="mim-font">
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Other entities represented in this entry:
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<span class="h3 mim-font">
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NEURONAL CEROID LIPOFUSCINOSIS, INFANTILE, INCLUDED; INCL, INCLUDED
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SANTAVUORI DISEASE, INCLUDED<br />
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SANTAVUORI-HALTIA DISEASE, INCLUDED
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<strong>SNOMEDCT:</strong> 58258004;
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<strong>ORPHA:</strong> 228329;
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<strong>DO:</strong> 0110721;
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<h4>
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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<th>
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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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</thead>
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<tbody>
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<span class="mim-font">
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1p34.2
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<span class="mim-font">
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Ceroid lipofuscinosis, neuronal, 1
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</td>
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<span class="mim-font">
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256730
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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<td>
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<span class="mim-font">
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PPT1
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<span class="mim-font">
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600722
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</table>
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<span class="mim-font">
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<strong>TEXT</strong>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because neuronal ceroid lipofuscinosis-1 (CLN1) is caused by homozygous or compound heterozygous mutation in the gene encoding palmitoyl-protein thioesterase-1 (PPT1; 600722) on chromosome 1p34.</p>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<p>The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). The patterns most often observed in CLN2 and CLN3 are 'curvilinear' and 'fingerprint' profiles, respectively. CLN4, CLN5, CLN6, CLN7, and CLN8 show mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). </p><p>Zeman and Dyken (1969) referred to these conditions as the 'neuronal ceroid lipofuscinoses.' Goebel (1995) provided a comprehensive review of the NCLs and noted that they are possibly the most common group of neurodegenerative diseases in children. </p><p>Mole et al. (2005) provided a detailed clinical and genetic review of the neuronal ceroid lipofuscinoses. </p><p><strong><em>Genetic Heterogeneity of Neuronal Ceroid Lipofuscinosis</em></strong></p><p>
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See also CLN2 (204500), caused by mutation in the TPP1 gene (607998) on chromosome 11p15; CLN3 (204200), caused by mutation in the CLN3 gene (607042) on 16p12; CLN4 (162350), caused by mutation in the DNAJC5 gene (611203) on 20q13; CLN5 (256731), caused by mutation in the CLN5 gene (608102) on 13q22; CLN6A (601780) and CLN6B (204300), both caused by mutation in the CLN6 gene (606725) on 15q21; CLN7 (610951), caused by mutation in the MFSD8 gene (611124) on 4q28; CLN8 (600143) and the Northern epilepsy variant of CLN8 (610003), both caused by mutation in the CLN8 gene (607837) on 8p23; CLN10 (610127), caused by mutation in the CTSD gene (116840) on 11p15; CLN11 (614706), caused by mutation in the GRN gene (138945) on 17q21; CLN13 (615362), caused by mutation in the CTSF gene (603539) on 11q13; and CLN14 (611726), caused by mutation in the KCTD7 gene (611725) on 7q11.</p><p>CLN9 (609055) has not been molecularly characterized.</p><p>A disorder that was formerly designated neuronal ceroid lipofuscinosis-12 (CLN12) is now considered to be a variable form of Kufor-Rakeb syndrome (KRS; 606693).</p>
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<h4>
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<span class="mim-font">
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<strong>Nomenclature</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The CLNs were originally classified broadly by age at onset: CLN1 as the infantile-onset form, or the infantile-onset Finnish form, having first been described in that population; CLN2 as the late infantile-onset form; CLN3 as the juvenile-onset form; and CLN4 as the adult-onset form. With the identification of molecular defects, however, the CLNs are now classified numerically according to the underlying gene defect. CLN1 refers to CLN caused by mutation in the PPT1 gene, regardless of the age at onset (Mole et al., 2005). </p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Classic Infantile-Onset CLN1</em></strong></p><p>
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Hagberg et al. (1968) described 'progressive encephalopathy' in a child of unrelated Finnish parents. The disorder was characterized by mental retardation, loss of speech, minor motor seizures, regression of motor development, and ataxia. Histologically, the brain showed total derangement of cortical cytoarchitecture, severe degeneration of white matter, and deposits of granular material suggesting free fatty acids and unsaturated fatty acids. Biochemical studies showed a disturbance of linoleic acid metabolism. </p><p>Santavuori et al. (1973) and Haltia et al. (1973) characterized the distinctive clinical and morphologic features of infantile-onset CLN1, respectively. Morphologic findings included severe neuronal destruction with massive accumulations of phagocytes, often binucleated, and unusually hypertrophic fibrillary astrocytes in the cerebral cortex. The fatty acid pattern of serum lecithin showed an increase of arachidonic acid and corresponding decrease of linoleic acid. </p><p>Santavuori et al. (1974) reported that infantile-onset CLN is clinically homogeneous in the Finnish population. After normal development, visual failure, speech and motor deterioration, and seizures appeared between the ages of 6 and 24 months. Most patients had no cortical activity demonstrable by EEG by age 3 years. At least 55 cases of the same abnormality were identified in Finland (Hagberg, 1974). Age at onset ranged from 8 to 18 months with rapid psychomotor deterioration, ataxia, and muscular hypotonia. Other features included microcephaly and myoclonic jerks; convulsions were less common. Affected individuals were blind by age 2 years with optic atrophy and macular and retinal changes but no pigment aggregation. Both the ERG and the EEG showed early extinction. </p><p>Baumann and Markesbery (1982) stated that about 60 cases of 'Santavuori disease' had been reported. They described the first American cases: 3 cases in 2 unrelated families. A brother and sister were from Appalachian Kentucky. Features were early developmental deterioration, retinal blindness, microcephaly, and seizures. Baumann and Markesbery (1982) found characteristic inclusion material in circulating leukocytes. This material was electron microscopically identical to that in brain tissues and was apparently unique to Santavuori disease. </p><p>Vanhanen et al. (1995) reviewed the MRI appearance of the brain in 21 patients with infantile neuronal ceroid lipofuscinosis and compared them to 46 neurologically normal controls. MRI abnormalities were detectable before clinical symptoms and changed with the progression of the disease. In the early stage there was generalized cerebral atrophy, thalamic hypointensity to the white matter and to the basal ganglia, and thin periventricular high-signal rims from 13 months onward on T2-weighted images. They noted a pathognomonic appearance in patients older than 4 years of age, and found that the signal intensity of the gray matter on T2-weighted images was less than that of the white matter, or reverse of the normal appearance. </p><p><strong><em>Late Infantile- and Juvenile-Onset CLN1</em></strong></p><p>
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Becker et al. (1979) described the child of a consanguineous German couple who developed onset of mental and visual disturbances at age 3 years, followed by ataxia and myoclonic jerks. The chemical changes were those of the infantile form, but the electron microscopy of muscle and skin and the clinical course were more consistent with classically described later-onset forms of CLN (e.g., CLN2 or CLN3). </p><p>Philippart et al. (1995) and Hofman and Taschner (1995) described a variant of juvenile-onset CLN in which electron microscopy demonstrated intracellular fine granular osmiophilic deposits (GROD) characteristic of the infantile subtype. Curvilinear and fingerprint bodies, characteristic of other forms of CLN were not identified. Learning disabilities began between ages 6 and 10 years, but visual failure was delayed until age 10 to 14 years. Linkage analysis of 1 family excluded markers on chromosome 16p12 associated with CLN3. </p><p>Mitchison et al. (1998) reported 11 patients with juvenile-onset of CLN with GROD, including those reported by Philippart et al. (1995) and Hofman and Taschner (1995). Deterioration of intellect began between ages 7 and 13 years, deterioration of motor function between ages 7 and 15 years, deterioration of vision between ages 6 and 14 years, and onset of EEG changes and epilepsy between ages 7 and 17 years. Vacuolated lymphocytes were not detected in 11 of 16 patients. The tissues in which granular osmiophilic deposits were observed included skin, conjunctiva, rectum, and blood. </p><p>Wisniewski et al. (1998) reported 5 patients from 3 unrelated families with late infantile-onset CLN1 with GROD. PPT1 activity was less than 10% of normal values, suggesting a variant form of CLN1. </p><p>Das et al. (1998) found excellent correlation between absence of PPT1 activity and GROD histology among 32 unrelated individuals with CLN. All 23 patients with pure GROD and 6 (67%) of 9 patients with GROD mixed with curvilinear or fingerprint inclusions had decreased PPT1 activity. Fourteen patients had infantile onset before 24 months of age, 5 had late-infantile onset between ages 2 and 4, and 13 had juvenile onset after age 5 years. The 3 patients with normal PPT1 activity all had juvenile-onset CLN; 1 of these patients was subsequently found to have mutations in the CLN3 gene (607042). Twenty-eight patients with CLN without GROD histology all had normal PPT1 activity. The patients included the 3 probands reported by Wisniewski et al. (1998). </p><p><strong><em>Adult-Onset CLN1</em></strong></p><p>
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Van Diggelen et al. (2001) reported 2 sisters with adult-onset neuronal CLN1 confirmed by the finding of compound heterozygous mutations in the PPT1 gene (600722.0006; 600722.0009). Onset in both patients was in the thirties, with symptoms of depression progressing to cognitive decline, cerebellar ataxia, parkinsonism, and decreased verbal fluency in their fifties. Both patients showed generalized brain atrophy on MRI. Enzyme analysis showed severe PPT deficiency. </p><p>Ramadan et al. (2007) reported a 24-year-old woman who presented with psychiatric features, including low mood, irritability, lack of interest, bizarre behavior, and academic decline. She deteriorated over the next 18 months, developing tunnel vision, retinitis pigmentosa, visual hallucinations, and further cognitive decline. Brain MRI showed marked generalized cerebral and cerebellar atrophy. Skin and rectal mucosal biopsies showed a storage disease with autofluorescent granular osmiophilic deposits, and biochemical studies showed decreased PPT1 activity. Genetic analysis identified compound heterozygosity for 2 mutations in the PPT1 gene (600722.0006; 600722.0010). Ramadan et al. (2007) emphasized the late onset in this patient and noted the similarities to the sisters reported by Van Diggelen et al. (2001). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By linkage analysis in Finnish families with infantile-onset CLN1, Jokiaho et al. (1990) excluded linkage to chromosome 16, where the gene for Batten disease (CLN3) had been mapped. </p><p>In studies of 15 Finnish families with infantile-onset CLN1, Jarvela et al. (1991) demonstrated linkage to chromosome 1p (maximum lod scores of 3.38 for D1S57, 3.56 for D1S7, and 3.56 for D1S79). Jarvela (1991) presented a map of the birthplaces of great-grandparents of 35 patients with CLN1. The wide distribution of this ancestry suggested a very old founder effect. On the basis of further linkage studies, Jarvela et al. (1991) mapped the CLN1 gene to chromosome 1p32. </p><p>Hellsten et al. (1993) observed linkage disequilibrium between CLN1 and a newly discovered, highly polymorphic marker. Incorporation of the observed linkage disequilibrium into multipoint linkage analysis significantly increased the informativeness of the limited family material and facilitated refined assignment of the CLN1 locus. Hellsten et al. (1995) constructed a pulsed field gel electrophoresis (PFGE) map of 4 Mb in the region of the CLN1 gene. They established the order of several loci at 1p32 by combining data obtained from analysis of a chromosome 1 somatic cell hybrid panel, PFGE, and interphase fluorescence in situ hybridization. They found that a 1-Mb contig contained MYCL1, the HY-TM1 marker closely linked to CLN1, RLF (180610), and COL9A2 (120260). Within the contig, they identified 5 CpG islands, in addition to those associated with the earlier cloned genes. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Voznyi et al. (1999) reported a new fluorimetric assay for PPT activity based on the fluorochrome 4-methylumbelliferone. PPT1 activity was detectable in fibroblasts, leukocytes, lymphoblasts, amniotic fluid cells, and chorionic villi, but was deficient in tissues from CLN1 patients. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
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De Vries et al. (1999) reported prenatal diagnosis of CLN1 by chorionic villi sampling. PPT1 activity was deficient and molecular analysis identified a homozygous mutation in the PPT1 gene (600722.0008). The pregnancy was terminated and the PPT deficiency was confirmed in cultured chorionic villi cells as well as in cultured fetal skin fibroblasts. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The transmission pattern of CLN1 in the Finnish families reported by Vesa et al. (1995) was consistent with autosomal recessive inheritance. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By positional candidate gene methods, Vesa et al. (1995) identified a homozygous mutation (R122W; 600722.0001) in the PPT1 gene in patients with infantile-onset CLN1 from 40 of 42 Finnish families. The findings were consistent with a founder effect. </p><p>Mitchison et al. (1998) identified homozygosity or compound heterozygosity for mutations in the PPT1 gene (600722.0002-600722.0006) in 11 patients with juvenile-onset CLN1 with the ultrastructural findings of granular osmiophilic deposits. </p><p>Das et al. (1998) identified 19 different mutations in the PPT1 gene in 57 of 58 mutated alleles from 29 patient-derived cell lines. The R151X mutation (600722.0006) accounted for 40% of the alleles, and the T75P mutation (600722.0002) accounted for 13% of the alleles. Fifty percent of patients had infantile onset, 17% had late-infantile onset, and 33% had juvenile onset. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kim et al. (2006) noted that apoptosis is 1 of the major causes of neurodegeneration in INCL. In a follow-up to studies in a mouse model of CLN1 that showed activation of the endoplasmic reticulum stress response (Zhang et al., 2006), Kim et al. (2006) studied signals of apoptosis in brain samples from a patient with CLN1. Brain tissue showed increased levels of mitochondrial superoxide dismutase-2 (SOD2; 147460), caspase-9 (CASP9; 602234), caspase-3 (CASP3; 600636), and cleaved PARP1 (173870) compared to control brain samples. These findings were consistent with rapid neuronal death by apoptosis. Studies of Ppt1-null mice revealed similar patterns, and studies of cultured neurospheres indicated that ER stress caused elevated levels of reactive oxygen species (ROS). Kim et al. (2006) proposed that the rapid progression of neurodegeneration in human INCL is likely to be caused by ER stress-mediated caspase-12 (CASP12; 608633) activation as well as by elevated ROS production, which stimulates SOD2 production and destabilization of calcium homeostasis. Together these abnormalities mediate activation of CASP9, CASP3, and cleavage of PARP, which is indicative of apoptosis. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>CLN1 is most common in populations of Finnish descent, with an incidence of 1:20,000 and a carrier frequency of 1 in 70 (summary by Miller et al., 2015). </p>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Gupta et al. (2001) engineered disruptions in the Ppt1 and Ppt2 (603298) genes to create knockout mice that were deficient in either enzyme. Both lines of mice were viable and fertile; however, both lines developed spasticity (a 'clasping' phenotype) at a median age of 21 weeks and 29 weeks, respectively. Motor abnormalities progressed in the Ppt1 knockout mice, leading to death by 10 months of age. In contrast, most Ppt2 mice were alive at 12 months. Myoclonic jerking and seizures were prominent in the Ppt1 mice. Autofluorescent storage material was striking throughout the brains of both strains of mice. Neuronal loss and apoptosis were particularly prominent in Ppt1-deficient brains. These studies provided a mouse model for infantile neuronal ceroid lipofuscinosis and further suggested that PPT2 serves a role in the brain that is not carried out by PPT1. </p><p>Zhang et al. (2006) reported that the brains of Ppt1-null mice accumulated autofluorescent material, abnormalities of the neuronal endoplasmic reticulum (ER), and showed progressive neuronal apoptosis that correlated with neurologic motor impairment. There was an abnormal accumulation of palmitoylated GAP43 (162060) in the ER. Increased levels of this and other S-acylated proteins coincided with activation of the unfolded protein response, characterized by increased phosphorylation of EIF2A (609234) and activation of CASP12, which ultimately leads to cellular apoptosis. Zhang et al. (2006) concluded that PPT1 deficiency leads to neurodegeneration by activation of the unfolded protein response as a result of abnormal accumulation of palmitoylated proteins. </p><p>Neural communication relies on repeated cycles of exo- and endocytosis of synaptic vesicles containing neurotransmitters at the plasma membranes of nerve terminals. In the mouse brain, Kim et al. (2008) found that Ppt1 localized in the synaptosomes and synaptic vesicles of the presynaptic compartment under physiologic conditions. Ppt1 deficiency resulted in abnormal and persistent membrane retention of palmitoylated synaptic vesicle-associated proteins, including VAMP2 (185881), SNAP25 (600322), syntaxin-1 (STX1A; 186590), SYTI (185605), and GAD65 (138275) in brain tissue from both human patients with neuronal lipofuscinosis and Ppt1-deficient mice. Since these S-acylated proteins must undergo depalmitoylation to detach from the membrane, which is required for recycling, Ppt1 deficiency may cause these proteins to remain membrane bound. Kim et al. (2008) proposed a mechanism by which PPT1 deficiency leads to the disruption of synaptic vesicle recycling, prevents the regeneration of fresh vesicles, and results in a progressive decline in the total pool size, which ultimately impairs neurotransmission. </p><p>Miller et al. (2015) generated a transgenic mouse model homozygous for the common R151X PPT1 mutation (600722.0006). The phenotype of the mutant mice recapitulated that observed in humans, including impaired motor function, decreased exploratory behavior, accumulation of autofluorescent material in the brain, and widespread astrogliosis and microglial activation throughout the brain. PPT1 enzyme activity in homozygous mice was 1.7 to 3.1% of controls. Administration of the read-through compound ataluren (PTC124) increased PPT1 enzyme activity and protein level in mutant mice in a proof-of-principle study. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>History</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Oppenheimer and Andrews (1959) reported 2 patients with 'ceroid storage disease': a 4-year-old white male from West Virginia who died from liver failure and had ceroid deposits of liver, spleen and intestinal mucosa, and a white 22-month-old female who at autopsy had ceroid limited largely to hepatic macrophages. The sister and 2 brothers reported by Nelson et al. (1961) may have had the same condition. The isolated case reported by Jonas (1966) may have had the same or a related condition. </p><p>Ryan et al. (1970) provided a detailed report of a boy with 'lipofuscin storage disease.' Menkes (1982) reviewed this paper and suggested, mainly on clinical grounds because the electron microscopy was unsatisfactory, that the correct diagnosis was the Finnish or Santavuori type of infantile neuronal ceroid lipofuscinosis. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Hagberg et al. (1974); Mole (1999); Santavuori (1980)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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<strong>Santavuori disease: diagnosis by leukocyte ultrastructure.</strong>
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Neurology 32: 1277-1281, 1982.
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Becker, K., Goebel, H.-H., Svennerholm, L., Wendel, U., Bremer, H. J.
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<strong>Clinical, morphological, and biochemical investigations on a patient with an unusual form of neuronal ceroid-lipofuscinosis.</strong>
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de Vries, B. B. A., Kleijer, W. J., Keulemans, J. L. M., Voznyi, Y. V., Franken, P. F., Eurlings, M. C. M., Galjaard, R. J., Losekoot, M., Catsman-Berrevoets, C. E., Breuning, M. H., Taschner, P. E. M., van Diggelen, O. P.
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J. Child Neurol. 10: 424-437, 1995.
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Gupta, P., Soyombo, A. A., Atashband, A., Wisniewski, K. E., Shelton, J. M., Richardson, J. A., Hammer, R. E., Hofmann, S. L.
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<strong>Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice.</strong>
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Proc. Nat. Acad. Sci. 98: 13566-13571, 2001.
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Hagberg, B., Haltia, M., Sourander, P., Svennerholm, L., Eeg-Olofsson, O.
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<strong>Polyunsaturated fatty acid lipidosis infantile form of so-called neuronal ceroid lipofuscinosis. I. Clinical and morphological aspects.</strong>
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Acta Paediat. Scand. 63: 753-763, 1974.
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[PubMed: 4415126]
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[Full Text: https://doi.org/10.1111/j.1651-2227.1974.tb17001.x]
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Hagberg, B., Sourander, P., Svennerholm, L.
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<strong>Late infantile progressive encephalopathy with disturbed poly-unsaturated fat metabolism.</strong>
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Acta Paediat. Scand. 57: 495-499, 1968.
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[PubMed: 5706364]
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[Full Text: https://doi.org/10.1111/j.1651-2227.1968.tb06968.x]
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<p class="mim-text-font">
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Hagberg, B.
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<strong>Personal Communication.</strong>
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Gotteborg, Sweden 9/4/1974.
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<p class="mim-text-font">
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Haltia, M., Rapola, J., Santavuori, P., Keranen, A.
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<strong>Infantile type of so-called neuronal ceroid-lipofuscinosis--Part 2. Morphological and biochemical studies.</strong>
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J. Neurol. Sci. 18: 269-285, 1973.
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[PubMed: 4121459]
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[Full Text: https://doi.org/10.1016/0022-510x(73)90076-2]
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<li>
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<p class="mim-text-font">
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Hellsten, E., Vesa, J., Heiskanen, M., Makela, T. P., Jarvela, I., Cowell, J. K., Mead, S., Alitalo, K., Palotie, A., Peltonen, L.
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<strong>Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus.</strong>
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Genomics 25: 404-412, 1995.
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[PubMed: 7789974]
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[Full Text: https://doi.org/10.1016/0888-7543(95)80040-s]
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<p class="mim-text-font">
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Hellsten, E., Vesa, J., Speer, M. C., Makela, T. P., Jarvela, I., Alitalo, K., Ott, J., Peltonen, L.
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<strong>Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: incorporation of linkage disequilibrium in multipoint analysis.</strong>
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Genomics 16: 720-725, 1993.
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[PubMed: 8325646]
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[Full Text: https://doi.org/10.1006/geno.1993.1253]
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Hofman, I. L., Taschner, P. E. M.
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<strong>Late onset juvenile neuronal ceroid-lipofuscinosis with granular osmiophilic deposits (GROD).</strong>
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Am. J. Med. Genet. 57: 165-167, 1995.
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[PubMed: 7668323]
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[Full Text: https://doi.org/10.1002/ajmg.1320570211]
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<p class="mim-text-font">
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Jarvela, I., Santavuori, P., Vesa, J., Rapola, J., Palotie, A., Peltonen, L.
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<strong>Assignment of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) to the short arm of chromosome 1 (Abstract)</strong>
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Cytogenet. Cell Genet. 58: 1856-1857, 1991.
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Jarvela, I., Schleutker, J., Haataja, L., Santavuori, P., Puhakka, L., Manninen, T., Palotie, A., Sandkuijl, L. A., Renlund, M., White, R., Aula, P., Peltonen, L.
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<strong>Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1.</strong>
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Genomics 9: 170-173, 1991.
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[PubMed: 1672288]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90235-7]
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Jarvela, I.
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<strong>Infantile neuronal ceroid lipofuscinosis (CLN1): linkage disequilibrium in the Finnish population and evidence that variant late infantile form (variant CLN2) represents a nonallelic locus.</strong>
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Genomics 10: 333-337, 1991.
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[PubMed: 2071142]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90316-7]
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Jokiaho, I., Puhakka, L., Santavuori, P., Manninen, T., Nyman, K., Peltonen, L.
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<strong>Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses.</strong>
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Genomics 8: 391-393, 1990.
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[PubMed: 2249855]
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<p class="mim-text-font">
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Jonas, O.
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<strong>Ceroid storage in a child with a Niemann-Pick type syndrome.</strong>
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Med. J. Aust. 2: 551-554, 1966.
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[PubMed: 5922340]
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[Full Text: https://doi.org/10.5694/j.1326-5377.1966.tb97330.x]
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Kim, S.-J., Zhang, Z., Lee, Y.-C., Mukherjee, A. B.
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<strong>Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.</strong>
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Hum. Molec. Genet. 15: 1580-1586, 2006.
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[PubMed: 16571600]
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[Full Text: https://doi.org/10.1093/hmg/ddl078]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kim, S.-J., Zhang, Z., Sarkar, C., Tsai, P.-C., Lee, Y.-C., Dye, L., Mukherjkee, A. B.
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<strong>Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice.</strong>
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J. Clin. Invest. 118: 3075-3086, 2008.
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[PubMed: 18704195]
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[Full Text: https://doi.org/10.1172/JCI33482]
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</p>
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<li>
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<p class="mim-text-font">
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Menkes, J. H.
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<strong>Personal Communication.</strong>
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Beverly Hills, Calif. 2/26/1982.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Miller, J. N., Kovacs, A. D., Pearce, D. A.
|
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<strong>The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.</strong>
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|
Hum. Molec. Genet. 24: 185-196, 2015.
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[PubMed: 25205113]
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[Full Text: https://doi.org/10.1093/hmg/ddu428]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mitchison, H. M., Hofmann, S. L., Becerra, C. H. R., Munroe, P. B., Lake, B. D., Crow, Y. J., Stephenson, J. B. P., Williams, R. E., Hofman, I. L., Taschner, P. E. M., Martin, J.-J., Philippart, M., Andermann, E., Andermann, F., Mole, S. E., Gardiner, R. M., O'Rawe, A. M.
|
|
<strong>Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits.</strong>
|
|
Hum. Molec. Genet. 7: 291-297, 1998. Note: Erratum: Hum. Molec. Genet. 7: 765 only, 1998.
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[PubMed: 9425237]
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[Full Text: https://doi.org/10.1093/hmg/7.2.291]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Mole, S. E., Williams, R. E., Goebel, H. H.
|
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<strong>Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.</strong>
|
|
Neurogenetics 6: 107-126, 2005.
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|
[PubMed: 15965709]
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[Full Text: https://doi.org/10.1007/s10048-005-0218-3]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mole, S. E.
|
|
<strong>Batten's disease: eight genes and still counting? (Commentary)</strong>
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|
Lancet 354: 443-445, 1999.
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[PubMed: 10465165]
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[Full Text: https://doi.org/10.1016/S0140-6736(99)00173-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Nelson, P., Santamaria, A., Olson, R. L., Nayak, N. C.
|
|
<strong>Generalized lymphohistiocytic infiltration: a familial disease not previously described and different from Letterer-Siwe disease and Chediak-Higashi syndrome.</strong>
|
|
Pediatrics 27: 931-950, 1961.
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|
[PubMed: 13728304]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Oppenheimer, E. H., Andrews, E. C., Jr.
|
|
<strong>Ceroid storage disease in childhood.</strong>
|
|
Pediatrics 23: 1091-1102, 1959.
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[PubMed: 13657591]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Philippart, M., Chugani, H. T., Bateman, J. B.
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<strong>New Spielmeyer-Vogt variant with granular inclusions and early brain atrophy.</strong>
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Am. J. Med. Genet. 57: 160-164, 1995.
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[PubMed: 7668322]
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[Full Text: https://doi.org/10.1002/ajmg.1320570210]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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