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<title>
Entry
- #235400 - HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1; AHUS1
- OMIM
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<span class="h4">#235400</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/235400"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS235400"> <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="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=HEMOLYTIC UREMIC SYNDROME, ATYPICAL" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=779&Typ=Pat" title="Atypical hemolytic uremic syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Atypical hemolytic uremic …&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=28081&Typ=Pat" title="Atypical hemolytic uremic syndrome with complement gene abnormality" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Atypical hemolytic uremic …&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11935&Typ=Pat" title="Shiga toxin-associated hemolytic uremic syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Shiga toxin-associated hem…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12421&Typ=Pat" title="Atypical hemolytic uremic syndrome with anti-factor H antibodies" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Atypical hemolytic uremic …&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1367/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=235400[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2134" title="Atypical hemolytic uremic syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Atypical hemolytic uremic …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=544472" title="Atypical hemolytic uremic syndrome with complement gene abnormality" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Atypical hemolytic uremic …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90038" title="Shiga toxin-associated hemolytic uremic syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Shiga toxin-associated hem…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93581" title="Atypical hemolytic uremic syndrome with anti-factor H antibodies" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Atypical hemolytic uremic …</a></div>
</div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://omia.org/OMIA000636/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ORPHA:</strong> 2134, 544472, 90038, 93581<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
235400
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1; AHUS1
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
AHUS, SUSCEPTIBILITY TO, 1
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
HEMOLYTIC UREMIC SYNDROME, TYPICAL, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1528?start=-3&limit=10&highlight=1528">
1q31.3
</a>
</span>
</td>
<td>
<span class="mim-font">
{Hemolytic uremic syndrome, atypical, susceptibility to, 1}
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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">
CFH
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134370"> 134370 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1529?start=-3&limit=10&highlight=1529">
1q31.3
</a>
</span>
</td>
<td>
<span class="mim-font">
{Hemolytic uremic syndrome, atypical, susceptibility to}
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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">
CFHR3
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605336"> 605336 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1530?start=-3&limit=10&highlight=1530">
1q31.3
</a>
</span>
</td>
<td>
<span class="mim-font">
{Hemolytic uremic syndrome, atypical, susceptibility to}
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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">
CFHR1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134371"> 134371 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/235400" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS235400" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/235400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/235400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br /> -
Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertension (especially in atypical hemolytic-uremic syndrome (aHUS)) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856150</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Prodrome of gastroenteric diarrhea, usually caused by E. coli 0157-H7 or shigella in young children (typical HUS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550379</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Acute renal failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14669001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14669001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N17</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N17.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N17.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/584" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">584</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/584.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">584.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022660&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022660</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001919</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001919</a>]</span><br /> -
Anuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2472002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2472002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2188545&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2188545</a>, <a href="https://bioportal.bioontology.org/search?q=C0003460&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003460</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100519" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100519</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100519" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100519</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Global and focal neurologic abnormalities (less than 30%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856144&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856144</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 /> -
Coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/371632003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">371632003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405809000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405809000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0543874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0543874</a>, <a href="https://bioportal.bioontology.org/search?q=C3146279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3146279</a>, <a href="https://bioportal.bioontology.org/search?q=C0009421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span><br /> -
Hemiparesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20022000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20022000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018989&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018989</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001269" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001269</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001269" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001269</a>]</span><br /> -
Cognitive defects <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386806002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386806002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338656&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338656</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br /> -
Visual defects <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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3665347&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665347</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span><br /> -
Dysphasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20301004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20301004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229746007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229746007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R47.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R47.02</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0973461&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0973461</a>, <a href="https://bioportal.bioontology.org/search?q=C0454651&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0454651</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Fever <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386661006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386661006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/50177009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">50177009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015967&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015967</a>, <a href="https://bioportal.bioontology.org/search?q=C0424755&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424755</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001945" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001945</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001945" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001945</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Microangiopathic hemolytic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/373420004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">373420004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51071000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51071000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D59.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D59.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1268935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1268935</a>, <a href="https://bioportal.bioontology.org/search?q=C0221021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221021</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001937</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001937</a>]</span><br /> -
Thrombocytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br /> -
Thrombotic microangiopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/126729006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">126729006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M31.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M31.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/446.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">446.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2717961&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2717961</a>]</span><br /> -
Reticulocytosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/46049004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">46049004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0206160&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0206160</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001923" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001923</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001923" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001923</a>]</span><br /> -
Schistocytes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/385472000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">385472000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70310009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70310009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221282&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221282</a>, <a href="https://bioportal.bioontology.org/search?q=C0344386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344386</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001981" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001981</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001981" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001981</a>]</span><br /> -
'Burr cells' <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51384001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51384001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221279</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Complement component consumption <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749605</a>]</span><br /> -
Defective complement regulation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749606&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749606</a>]</span><br /> -
Activation of the complement system <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749607&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749607</a>]</span><br /> -
Some patients may have autoantibodies to factor H, resulting in functional factor H deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749608</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Decreased hemoglobin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165397008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165397008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162119&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162119</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001903" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001903</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001903" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001903</a>]</span><br /> -
Increased blood urea nitrogen (BUN) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151539&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151539</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003138</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003138</a>]</span><br /> -
Increased creatinine <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166717003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166717003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151578</a>, <a href="https://bioportal.bioontology.org/search?q=C0700225&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700225</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003259</a>]</span><br /> -
Decreased serum factor H (atypical HUS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856147</a>]</span><br /> -
Decreased serum factor I (atypical HUS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1968718&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1968718</a>]</span><br /> -
Decreased serum C3 (atypical HUS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856148&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856148</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005421</a>]</span><br /> -
Decreased serum factor B (atypical HUS) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1968719&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1968719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005416" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005416</a>]</span><br /> -
Hyperlipidemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55822004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55822004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166816003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166816003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3744001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3744001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E78.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E78.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0428465&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0428465</a>, <a href="https://bioportal.bioontology.org/search?q=C0020476&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020476</a>, <a href="https://bioportal.bioontology.org/search?q=C0020473&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020473</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010980" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010980</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0003077" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003077</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003077" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003077</a>]</span><br /> -
Normal activity of von Willebrand factor-cleaving protease <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856149&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856149</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Diarrhea-associated (D+HUS), occurs in children younger than 3 years, associated with verotoxin-producing E. coli (90% of patients) (typical HUS)<br /> -
D+HUS (typical HUS) is usually sporadic, limited to 1 event, and has a good prognosis<br /> -
Diarrhea-negative subtype (D-HUS), or atypical HUS, is more severe and often relapses<br /> -
D-HUS is usually familial<br /> -
Phenotypic overlap with thrombotic thrombocytopenic purpura (TTP, <a href="/entry/274150">274150</a>)<br /> -
May be triggered by medications, including antineoplastic agents, immunotherapeutic agents, and antiplatelet agents<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Susceptibility conferred by mutation in the complement factor H gene (CHF, <a href="/entry/134370#0001">134370.0001</a>)<br /> -
Susceptibility conferred by deletion that includes the complement factor H-related 1 gene (CFHR1, <a href="/entry/134371#0001">134371.0001</a>) and complement factor H-related 3 gene (CFHR3, <a href="/entry/605366#0001">605366.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Hemolytic uremic syndrome
- <a href="/phenotypicSeries/PS235400">PS235400</a>
- 11 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/1/1528?start=-3&limit=10&highlight=1528"> 1q31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> {Hemolytic uremic syndrome, atypical, susceptibility to, 1} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134370"> CFH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134370"> 134370 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1529?start=-3&limit=10&highlight=1529"> 1q31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> {Hemolytic uremic syndrome, atypical, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605336"> CFHR3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605336"> 605336 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1530?start=-3&limit=10&highlight=1530"> 1q31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/235400"> {Hemolytic uremic syndrome, atypical, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/235400"> 235400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134371"> CFHR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/134371"> 134371 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1659?start=-3&limit=10&highlight=1659"> 1q32.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612922"> {Hemolytic uremic syndrome, atypical, susceptibility to, 2} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/612922"> 612922 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120920"> MCP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120920"> 120920 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/482?start=-3&limit=10&highlight=482"> 4q25 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612923"> {Hemolytic uremic syndrome, atypical, susceptibility to, 3} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/612923"> 612923 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/217030"> CFI </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/217030"> 217030 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/343?start=-3&limit=10&highlight=343"> 6p21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612924"> {Hemolytic uremic syndrome, atypical, susceptibility to, 4} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/612924"> 612924 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138470"> CFB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138470"> 138470 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/769?start=-3&limit=10&highlight=769"> 17q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615008"> Nephrotic syndrome, type 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/615008"> 615008 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601440"> DGKE </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601440"> 601440 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/769?start=-3&limit=10&highlight=769"> 17q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615008"> {Hemolytic uremic syndrome, atypical, susceptibility to, 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/615008"> 615008 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601440"> DGKE </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601440"> 601440 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/189?start=-3&limit=10&highlight=189"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612925"> {Hemolytic uremic syndrome, atypical, susceptibility to, 5} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/612925"> 612925 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120700"> C3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120700"> 120700 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/145?start=-3&limit=10&highlight=145"> 20p11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612926"> {Hemolytic uremic syndrome, atypical, susceptibility to, 6} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/612926"> 612926 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188040"> THBD </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188040"> 188040 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/630?start=-3&limit=10&highlight=630"> Xq24 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301110"> Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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/301110"> 301110 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300611"> C1GALT1C1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300611"> 300611 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<p>A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-1 (AHUS1) can be conferred by variation in the gene encoding complement factor H (CFH; <a href="/entry/134370">134370</a>) on chromosome 1q31.</p><p>Deficiency of the CFH-related proteins CFHR1 (<a href="/entry/134371">134371</a>) and CFHR3 (<a href="/entry/605336">605336</a>) may be associated with development of the disorder due to autoantibodies. Other genes may play a role in modifying the phenotype (see MOLECULAR GENETICS).</p><p>HUS can share overlapping clinical features with thrombotic thrombocytopenic purpura (TTP; <a href="/entry/274150">274150</a>), which is caused by mutation in the von Willebrand factor-cleaving protease (VWFCP) gene (ADAMTS13; <a href="/entry/604134">604134</a>).</p>
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<p>Typical hemolytic uremic syndrome is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes ('burr cells'). The vast majority of cases (90%) are sporadic, occur in children under 3 years of age, and are associated with epidemics of diarrhea caused by verotoxin-producing E. coli. The death rate is very low, about 30% of cases have renal sequelae, and there is usually no relapse of the disease. This form of HUS usually presents with a diarrhea prodrome (thus referred to as D+HUS) and has a good prognosis in most cases. In contrast, a subgroup of patients with HUS have an atypical presentation (aHUS or D-HUS) without a prodrome of enterocolitis and diarrhea and have a much poorer prognosis, with a tendency to relapse and frequent development of end-stage renal failure or death. These cases tend to be familial. Both autosomal recessive and autosomal dominant inheritance have been reported (<a href="#18" class="mim-tip-reference" title="Goodship, J., Warwicker, P., Pirson, Y., Nicholls, A., Turnpenny, P., Goodship, T. &lt;strong&gt;Haemolytic uremic syndrome maps to chromosome 1q and is associated with mutations in the complement factor H gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 61 (suppl.): A56 only, 1997."None>Goodship et al., 1997</a>; <a href="#52" class="mim-tip-reference" title="Taylor, C. M. &lt;strong&gt;Hemolytic-uremic syndrome and complement factor H deficiency: clinical aspects.&lt;/strong&gt; Semin. Thromb. Hemost. 27: 185-190, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11446651/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11446651&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2001-15247&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11446651">Taylor, 2001</a>; <a href="#55" class="mim-tip-reference" title="Veyradier, A., Obert, B., Haddad, E., Cloarec, S., Nivet, H., Foulard, M., Lesure, F., Delattre, P., Lakhdari, M., Meyer, D., Girma, J.-PO., Loirat, C. &lt;strong&gt;Severe deficiency of the specific von Willebrand factor-cleaving protease (ADAMTS 13) activity in a subgroup of children with atypical hemolytic uremic syndrome.&lt;/strong&gt; J. Pediat. 142: 310-317, 2003. Note: Erratum: J. Pediat. 142: 616 only, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12640381/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12640381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2003.79&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12640381">Veyradier et al., 2003</a>; <a href="#37" class="mim-tip-reference" title="Noris, M., Brioschi, S., Caprioli, J., Todeschini, M., Bresin, E., Porrati, F., Gamba, S., Remuzzi, G. &lt;strong&gt;Familial haemolytic uraemic syndrome and an MCP mutation.&lt;/strong&gt; Lancet 362: 1542-1547, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14615110/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14615110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14742-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14615110">Noris et al., 2003</a>). <a href="#38" class="mim-tip-reference" title="Noris, M., Remuzzi, G. &lt;strong&gt;Atypical hemolytic-uremic syndrome.&lt;/strong&gt; New Eng. J. Med. 361: 1676-1687, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19846853/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19846853&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMra0902814&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19846853">Noris and Remuzzi (2009)</a> provided a detailed review of atypical HUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11446651+12640381+19846853+14615110" 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 Atypical Hemolytic Uremic Syndrome</em></strong></p><p>
Atypical HUS is a genetically heterogeneous condition. Susceptibility to the development of the disorder can be conferred by mutations in various components of or regulatory factors in the complement cascade system (<a href="#24" class="mim-tip-reference" title="Jozsi, M., Licht, C., Strobel, S., Zipfel, S. L. H., Richter, H., Heinen, S., Zipfel, P. F., Skerka, C. &lt;strong&gt;Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.&lt;/strong&gt; Blood 111: 1512-1514, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18006700/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18006700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2007-09-109876&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18006700">Jozsi et al., 2008</a>). See AHUS2 (<a href="/entry/612922">612922</a>), AHUS3 (<a href="/entry/612923">612923</a>), AHUS4 (<a href="/entry/612924">612924</a>), AHUS5 (<a href="/entry/612925">612925</a>), and AHUS6 (<a href="/entry/612926">612926</a>). AHUS7 (see <a href="/entry/615008">615008</a>) is caused by mutation in the DGKE gene (<a href="/entry/601440">601440</a>), which is not part of the complement cascade system. AHUS8 (<a href="/entry/301110">301110</a>) is caused by mutation in the C1GALT1C1 gene (<a href="/entry/300611">300611</a>), encoding a molecular chaperone with an essential role in mucin-type O-glycan biosynthesis, on chromosome Xq23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18006700" 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="#20" class="mim-tip-reference" title="Hagge, W. W., Holley, K. E., Burke, E. C., Stickler, G. B. &lt;strong&gt;Hemolytic-uremic syndrome in two siblings.&lt;/strong&gt; New Eng. J. Med. 277: 138-139, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6054994/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6054994&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196707202770306&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6054994">Hagge et al. (1967)</a> reported the hemolytic uremic syndrome in 2 sibs. Features included intravascular hemolysis, thrombocytopenia, and azotemia. One had repeated attacks ending in renal failure and death at age 8 years; the other recovered completely after one attack. <a href="#10" class="mim-tip-reference" title="Chan, J. C. M., Eleff, M. G., Campbell, R. A. &lt;strong&gt;The hemolytic-uremic syndrome in nonrelated adopted siblings.&lt;/strong&gt; J. Pediat. 75: 1050-1053, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5352831/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5352831&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(69)80346-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5352831">Chan et al. (1969)</a> reported HUS in 2 adopted, unrelated sibs. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6054994+5352831" 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="#25" class="mim-tip-reference" title="Kaplan, B. S., Chesney, R. W., Drummond, K. N. &lt;strong&gt;Hemolytic uremic syndrome in families.&lt;/strong&gt; New Eng. J. Med. 292: 1090-1093, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1128552/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1128552&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197505222922102&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1128552">Kaplan et al. (1975)</a> reported HUS in 3 sibs and reviewed reports of 21 sibships with 2 or more affected individuals. Two groups of families could be identified among 41 analyzed. Sibs whose onset was within a short time of each other had a relatively good prognosis (19% mortality). Those whose onset was more than a year apart had a poorer prognosis (68% mortality). <a href="#25" class="mim-tip-reference" title="Kaplan, B. S., Chesney, R. W., Drummond, K. N. &lt;strong&gt;Hemolytic uremic syndrome in families.&lt;/strong&gt; New Eng. J. Med. 292: 1090-1093, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1128552/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1128552&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197505222922102&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1128552">Kaplan et al. (1975)</a> suggested that an environmental agent was causative in the first group and that genetic factors were important in the second. Most of the first group of families came from an endemic area, whereas most of the second group came from a nonendemic area. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1128552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Blattler, W., Wegmann, W., Herold, H., Straub, P. W. &lt;strong&gt;Familiaeres haemolytisch-uraemisches Syndrom: Untersuchungen zur Pathogenesis bei den Ueberlebenden.&lt;/strong&gt; Schweiz. Med. Wschr. 105: 1773-1774, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1215973/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1215973&lt;/a&gt;]" pmid="1215973">Blattler et al. (1975)</a> studied a family in which 4 sibs had died from HUS. The parents and 4 surviving sibs had normal renal function and normal platelet and fibrinogen survival. The mother and 3 sibs had an increased percentage of megathrombocytes. Two of them showed renal accumulation of Cr 51-platelet radioactivity and ultrastructural changes of the endothelium on renal biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1215973" 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="#14" class="mim-tip-reference" title="Edelsten, A. D., Tuck, S. &lt;strong&gt;Familial haemolytic uraemic syndrome.&lt;/strong&gt; Arch. Dis. Child. 53: 255-256, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/646435/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;646435&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.53.3.255&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="646435">Edelsten and Tuck (1978)</a> reported a family with HUS inherited in an autosomal dominant pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=646435" 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="#53" class="mim-tip-reference" title="Thompson, R. A., Winterborn, M. H. &lt;strong&gt;Hypocomplementaemia due to a genetic deficiency of beta-1H globulin.&lt;/strong&gt; Clin. Exp. Immun. 46: 110-119, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6461451/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6461451&lt;/a&gt;]" pmid="6461451">Thompson and Winterborn (1981)</a> reported an 8-month-old Asian boy with very low levels of plasma factor H who presented with the hemolytic uremic syndrome. Complement component C3 (<a href="/entry/120700">120700</a>) was also depleted. A healthy 3-year-old brother had the same complement profile, suggesting activation of the alternative complement pathway. The parents, who were first cousins, had half-normal levels of factor H. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6461451" 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="Kirchner, K. A., Smith, R. M., Gockerman, J. P., Luke, R. G. &lt;strong&gt;Hereditary thrombotic thrombocytopenic purpura: microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency occurring in consecutive generations.&lt;/strong&gt; Nephron 30: 28-30, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7201082/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7201082&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000182427&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7201082">Kirchner et al. (1982)</a> described this disorder in mother and daughter. The daughter's illness, characterized primarily by renal insufficiency, was most compatible with adult hemolytic uremic syndrome and the mother's illness, with prominent neurologic findings, was most compatible with thrombotic thrombocytopenic purpura. <a href="#34" class="mim-tip-reference" title="Merrill, R. H., Knupp, C. L., Jennette, J. C. &lt;strong&gt;Familial thrombotic microangiopathy.&lt;/strong&gt; Quart. J. Med. 57: 749-759, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4080959/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4080959&lt;/a&gt;]" pmid="4080959">Merrill et al. (1985)</a> reported 2 certain cases and 3 possible case in 2 generations of a North Carolina black family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7201082+4080959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Neuhaus, T. J., Calonder, S., Leumann, E. P. &lt;strong&gt;Heterogeneity of atypical haemolytic uraemic syndromes.&lt;/strong&gt; Arch. Dis. Child. 76: 518-521, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9245850/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9245850&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.76.6.518&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9245850">Neuhaus et al. (1997)</a> reported clinical features of atypical D-HUS in 23 children. Features included requirement for dialysis (74%), hypertension (43%), cardiomyopathy (43%), and cerebral convulsions (48%). Only 5 patients (26%), including 4 infants, recovered completely. Six patients (32%) had 1 to 10 recurrences and 8 (42%) developed end-stage renal failure. Four children died. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245850" 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="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al. (1998)</a> reported a 36-year-old man with sporadic relapsing aHUS. He had anemia, thrombocytopenia, hypertension, and acute renal failure. Renal biopsy showed a thrombotic microangiopathy and deposition of complement component C3 in vessel walls. He had half-normal serum levels of factor H and decreased levels of C3, consistent with activation of the alternative complement pathway. HUS recurred after renal transplantation. Molecular analysis revealed a heterozygous 4-bp deletion in the CFH gene (<a href="/entry/134370#0011">134370.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9551389" 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="Ohali, M., Shalev, H., Schlesinger, M., Katz, Y., Kachko, L., Carmi, R., Sofer, S., Landau, D. &lt;strong&gt;Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H.&lt;/strong&gt; Pediat. Nephrol. 12: 619-624, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9811382/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9811382&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004670050515&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9811382">Ohali et al. (1998)</a> reported a large consanguineous Bedouin family in which 10 infants had atypical HUS characterized by microangiopathic hemolytic anemia, acute renal failure, severe hypertension, edema, and increased serum triglycerides. All had very early onset with a median presentation at age 2 weeks. Two patients died during the first disease episode; the remaining 8 patients had a mean number of 4 relapses despite treatment. In total, 8 patients died at ages 3 weeks to 10 months. Factor H levels were low to undetectable in all 4 patients studied, and C3 levels were decreased in 9 of 10 infants tested. Four kidney biopsies showed marked arteriolar changes, including stenosis, edema, and thickening of the intima. Glomerular changes included swelling of endothelial cells with microvillus transformation and proliferation of mesangial cells with increased matrix deposition in the mesangium. Other changes included fibrotic changes in glomeruli and the tubulointerstitium, as well as C3 deposition in capillary walls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9811382" 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="#48" class="mim-tip-reference" title="Rougier, N., Kazatchkine, M. D., Rougier, J.-P., Fremeaux-Bacchi, V., Blouin, J., Deschenes, G., Soto, B., Baudouin, V., Pautard, B., Proesmans, W., Weiss, E., Weiss, L. &lt;strong&gt;Human complement factor H deficiency associated with hemolytic uremic syndrome.&lt;/strong&gt; J. Am. Soc. Nephrol. 9: 2318-2326, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9848786/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9848786&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.V9122318&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9848786">Rougier et al. (1998)</a> reported 6 children with complement factor H deficiency and acute glomerular disease. Five of the 6 children presented with hemolytic uremic syndrome. Two of the children were from a consanguineous family from Turkey and exhibited a homozygous deficiency characterized by absence of the 150-kD form of factor H. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9848786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Noris, M., Brioschi, S., Caprioli, J., Todeschini, M., Bresin, E., Porrati, F., Gamba, S., Remuzzi, G. &lt;strong&gt;Familial haemolytic uraemic syndrome and an MCP mutation.&lt;/strong&gt; Lancet 362: 1542-1547, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14615110/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14615110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14742-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14615110">Noris et al. (2003)</a> reported a 21-year-old woman and her affected brother. Disease onset in the sister (the proband) was at age 16 months, when she developed fever, hemolytic anemia, and thrombocytopenia. At the time, renal function was normal. Thereafter she had 6 recurrences of thrombotic microangiopathy, all associated with deteriorating renal function. Treatment consisted of plasma exchange and infusions, steroids, and blood transfusions, which led to complete recovery of blood abnormalities and renal function. The last episode occurred at age 20 years and was characterized by anemia, thrombocytopenia, and severe impairment of renal function. Renal biopsy showed irreversible changes of chronic nephropathy with typical features of HUS, including diffuse narrowing/occlusion of vessels and severe glomerular ischemia. At the age of 21 years she was on chronic dialysis. The proband's brother had 2 episodes of HUS at age 9 years. Both were characterized by severe hemolytic anemia and acute renal insufficiency and resolved without plasma treatment, with no renal sequelae. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14615110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="clinicalManagement" class="mim-anchor"></a>
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<strong>Clinical Management</strong>
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<p><a href="#21" class="mim-tip-reference" title="Hazani, A., Eldor, A., Shechter, Y., Etzioni, A. &lt;strong&gt;Familial relapsing thrombotic micro-angiopathy in two siblings.&lt;/strong&gt; Europ. J. Pediat. 155: 99-101, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8775222/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8775222&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02075759&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8775222">Hazani et al. (1996)</a> reported relapsing thrombotic microangiopathy in a 12-year-old girl and her 7-year-old brother. During 11 years of follow-up, the girl responded only to steroids; many other therapeutic modalities were ineffective. Following treatment with low-dose danazol, relapses became fewer and less severe, completely subsiding after 6 months. The brother's illness began with signs of hemolytic uremic syndrome, with later development of neurologic manifestations. During a 6-year follow-up he responded only to plasma exchange. Although chronic thrombocytopenia persisted during the last 3 years, the boy's clinical condition improved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8775222" 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="Landau, D., Shalev, H., Levy-Finer, G., Polonsky, A., Segev, Y., Katchko, L. &lt;strong&gt;Familial hemolytic uremic syndrome associated with complement factor H deficiency.&lt;/strong&gt; J. Pediat. 138: 412-417, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11241053/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11241053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.112649&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11241053">Landau et al. (2001)</a> described 2 patients with atypical HUS associated with factor H deficiency. One patient who underwent renal transplantation for end-stage renal disease later had an extensive nonhemorrhagic cerebral infarction on 2 occasions and died in spite of multiple plasma transfusions. A second patient, a 14-month-old boy, experienced numerous HUS episodes starting at the age of 2 weeks. Daily plasma transfusions during relapses brought about only a temporary state of remission. However, prophylactic twice-weekly plasma therapy had been successful in preventing relapses and preserving renal function. <a href="#31" class="mim-tip-reference" title="Landau, D., Shalev, H., Levy-Finer, G., Polonsky, A., Segev, Y., Katchko, L. &lt;strong&gt;Familial hemolytic uremic syndrome associated with complement factor H deficiency.&lt;/strong&gt; J. Pediat. 138: 412-417, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11241053/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11241053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.112649&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11241053">Landau et al. (2001)</a> reported that with this regimen, serum factor H was increased from 6 mg/dL to subnormal values of 12 to 25 mg/dL (normal, greater than 60 mg/dL). <a href="#31" class="mim-tip-reference" title="Landau, D., Shalev, H., Levy-Finer, G., Polonsky, A., Segev, Y., Katchko, L. &lt;strong&gt;Familial hemolytic uremic syndrome associated with complement factor H deficiency.&lt;/strong&gt; J. Pediat. 138: 412-417, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11241053/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11241053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.112649&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11241053">Landau et al. (2001)</a> concluded that aHUS recurs because factor H deficiency is not corrected by renal transplantation. A hypertransfusion protocol may be useful. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Inheritance</strong>
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<p>Concordant monozygotic twins have been reported (<a href="#5" class="mim-tip-reference" title="Campbell, S., Carre, I. J. &lt;strong&gt;Fatal haemolytic uraemic syndrome and idiopathic hyperlipaemia in monozygotic twins.&lt;/strong&gt; Arch. Dis. Child. 40: 654-658, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5844955/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5844955&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.40.214.654&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5844955">Campbell and Carre, 1965</a>). <a href="#15" class="mim-tip-reference" title="Farr, M. J., Roberts, S., Morley, A. R., Dewar, P. J., Roberts, D. F., Uldall, P. R. &lt;strong&gt;The haemolytic uraemic syndrome--a family study.&lt;/strong&gt; Quart. J. Med. 44: 161-188, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1178809/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1178809&lt;/a&gt;]" pmid="1178809">Farr et al. (1975)</a> described a family with several affected members, including a father and his son and daughter. A common symptom was hypertension. They reviewed reports of familial occurrence. <a href="#41" class="mim-tip-reference" title="Perret, B., Gaze, H., Zimmermann, A., Oetliker, O. &lt;strong&gt;Syndrome hemolytique uremique familial non endemique: nephrectomie et transplantation.&lt;/strong&gt; Helv. Paediat. Acta 34: 167-176, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/378906/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;378906&lt;/a&gt;]" pmid="378906">Perret et al. (1979)</a> described this disorder in 5 members of 3 generations of a kindred and suggested genetic predisposition with a dominant gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=378906+1178809+5844955" 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 the study by <a href="#16" class="mim-tip-reference" title="Furlan, M., Robles, R., Galbusera, M., Remuzzi, G., Kyrle, P. A., Brenner, B., Krause, M., Scharrer, I., Aumann, V., Mittler, U., Solenthaler, M., Lammle, B. &lt;strong&gt;Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.&lt;/strong&gt; New Eng. J. Med. 339: 1578-1584, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9828245/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9828245&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199811263392202&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9828245">Furlan et al. (1998)</a>, there were multiple patients with the familial form of HUS: patients 44 and 45 were sister and brother and had 8 sibs who had died of acute HUS; patient 46 (a male) had 3 brothers who had died of HUS; from 2 other unrelated families, patients 47 and 48 were sisters and patients 49 and 50 were brothers; 1 brother and 1 sister of patient 51 had died of HUS; patients 52 and 53 were brother and sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Goodship, J., Warwicker, P., Pirson, Y., Nicholls, A., Turnpenny, P., Goodship, T. &lt;strong&gt;Haemolytic uremic syndrome maps to chromosome 1q and is associated with mutations in the complement factor H gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 61 (suppl.): A56 only, 1997."None>Goodship et al. (1997)</a> stated that most familial cases are recessive but dominant pedigrees had also been reported.</p><p>In a review of thrombotic microangiopathies, <a href="#35" class="mim-tip-reference" title="Moake, J. L. &lt;strong&gt;Thrombotic microangiopathies.&lt;/strong&gt; New. Eng. J. Med. 347: 589-600, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12192020/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12192020&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMra020528&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12192020">Moake (2002)</a> stated that 5 to 10% of cases of HUS are familial. The mortality rate (54%) is much higher in the familial form than in typical childhood HUS (3 to 5%). About half of the survivors have relapses and over one-third require long-term dialysis. Among patients with familial HUS who receive kidney allografts, 16% lose function in the engrafted kidney within 1 month. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12192020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="pathogenesis" class="mim-anchor"></a>
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<p><strong><em>Atypical Hemolytic Uremic Syndrome</em></strong></p><p>
Low levels of factor H in patients with aHUS were reported by <a href="#47" class="mim-tip-reference" title="Roodhooft, A. M., McLean, R. H., Elst, E., Van Acker, K. J. &lt;strong&gt;Recurrent haemolytic uraemic syndrome and acquired hypomorphic variant of the third component of complement.&lt;/strong&gt; Pediat. Nephrol. 4: 597-599, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2088459/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2088459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00858631&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2088459">Roodhooft et al. (1990)</a>, <a href="#42" class="mim-tip-reference" title="Pichette, V., Querin, S., Schurch, W., Brun, G., Lehner-Netsch, G., Delage, J. M. &lt;strong&gt;Familial hemolytic-uremic syndrome and homozygous factor H deficiency.&lt;/strong&gt; Am. J. Kidney Dis. 24: 936-941, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7985673/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7985673&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0272-6386(12)81065-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7985673">Pichette et al. (1994)</a>, and others. Some patients, however, may have normal levels of factor H, suggesting a dysfunction of the protein (<a href="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9551389+7985673+2088459" 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>Reduced serum C3 levels have been reported in sporadic (<a href="#50" class="mim-tip-reference" title="Stuhlinger, W., Kourilsky, O., Kanfer, A., Sraer, J. D. &lt;strong&gt;Haemolytic-uraemic syndrome: evidence for intravascular C3 activation. (Letter)&lt;/strong&gt; Lancet 304: 788-789, 1974. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4143056/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4143056&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(74)90991-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4143056">Stuhlinger et al., 1974</a>; <a href="#46" class="mim-tip-reference" title="Robson, W. L. M., Leung, A. K. C., Fick, G. H., McKenna, A. I. &lt;strong&gt;Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome.&lt;/strong&gt; Nephron 62: 296-299, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1436342/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1436342&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000187063&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1436342">Robson et al., 1992</a>) and familial HUS (<a href="#59" class="mim-tip-reference" title="Zachwieja, J., Strzykala, K., Golda, W., Maciejewski, J. &lt;strong&gt;Familial, recurrent haemolytic-uraemic syndrome with hypocomplementaemia. (Letter)&lt;/strong&gt; Pediat. Nephrol. 6: 221-222, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1571225/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1571225&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00866325&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1571225">Zachwieja et al., 1992</a>). In Italy, <a href="#39" class="mim-tip-reference" title="Noris, M., Ruggenenti, P., Perna, A., Orisio, S., Caprioli, J., Skerka, C., Vasile, B., Zipfel, P. F., Remuzzi, G. &lt;strong&gt;Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities.&lt;/strong&gt; J. Am. Soc. Nephrol. 10: 281-293, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10215327/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10215327&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.V102281&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10215327">Noris et al. (1999)</a> studied 6 families with HUS, 1 family with TTP, and 2 families with both disorders. Included in the study were 15 patients and 63 available healthy relatives as well as 25 age- and gender-matched healthy controls and 56 of their available relatives. Consanguinity was observed in 2 families. Seventy-three percent of the cases versus 16% of controls (P less than 0.001) as well as 24% of case-relatives versus 5% of control-relatives (P = 0.005) had decreased C3 levels, which were more marked in the actual cases. Factor H abnormalities were found in 4 of the 15 cases as compared with 3 of the 63 case-relatives and none of 17 healthy controls. All cases with factor H abnormalities had low C3 serum concentrations. <a href="#39" class="mim-tip-reference" title="Noris, M., Ruggenenti, P., Perna, A., Orisio, S., Caprioli, J., Skerka, C., Vasile, B., Zipfel, P. F., Remuzzi, G. &lt;strong&gt;Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities.&lt;/strong&gt; J. Am. Soc. Nephrol. 10: 281-293, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10215327/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10215327&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.V102281&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10215327">Noris et al. (1999)</a> concluded that reduced C3 in familial HUS is likely related to a genetically determined deficiency of factor H. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10215327+1571225+4143056+1436342" 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="#44" class="mim-tip-reference" title="Remuzzi, G., Galbusera, M., Noris, M., Canciani, M. T., Daina, E., Bresin, E., Contaretti, S., Caprioli, J., Gamba, S., Ruggenenti, P., Perico, N., Mannucci, P. M. &lt;strong&gt;von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.&lt;/strong&gt; Blood 100: 778-785, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12130486/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12130486&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2001-12-0166&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12130486">Remuzzi et al. (2002)</a> concluded that ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and that it is not the only determinant of VWF (<a href="/entry/613160">613160</a>) abnormalities in these conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12130486" 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 41 children with D+HUS and 23 children with D-HUS, <a href="#55" class="mim-tip-reference" title="Veyradier, A., Obert, B., Haddad, E., Cloarec, S., Nivet, H., Foulard, M., Lesure, F., Delattre, P., Lakhdari, M., Meyer, D., Girma, J.-PO., Loirat, C. &lt;strong&gt;Severe deficiency of the specific von Willebrand factor-cleaving protease (ADAMTS 13) activity in a subgroup of children with atypical hemolytic uremic syndrome.&lt;/strong&gt; J. Pediat. 142: 310-317, 2003. Note: Erratum: J. Pediat. 142: 616 only, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12640381/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12640381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2003.79&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12640381">Veyradier et al. (2003)</a> found that von Willebrand factor-cleaving protease activity was normal in over 50% of patients, but was undetectable in 1 D+HUS and 6 D-HUS children. After a 3-month remission, the D+HUS patient recovered 100% VWFCP activity, whereas the 6 D-HUS patients kept an undetectable level. In these 6 D-HUS patients, the disease was characterized by a neonatal onset and several relapses of hemolytic anemia, thrombocytopenia, acute renal failure, and cerebral ischemia. Arterial hypertension and end-stage renal failure sometimes occurred. <a href="#55" class="mim-tip-reference" title="Veyradier, A., Obert, B., Haddad, E., Cloarec, S., Nivet, H., Foulard, M., Lesure, F., Delattre, P., Lakhdari, M., Meyer, D., Girma, J.-PO., Loirat, C. &lt;strong&gt;Severe deficiency of the specific von Willebrand factor-cleaving protease (ADAMTS 13) activity in a subgroup of children with atypical hemolytic uremic syndrome.&lt;/strong&gt; J. Pediat. 142: 310-317, 2003. Note: Erratum: J. Pediat. 142: 616 only, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12640381/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12640381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2003.79&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12640381">Veyradier et al. (2003)</a> concluded that a subgroup of patients with D-HUS is related to VWFCP and may actually correspond to TTP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12640381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using in vitro expression studies, <a href="#32" class="mim-tip-reference" title="Manuelian, T., Hellwage, J., Meri, S., Caprioli, J., Noris, M., Heinen, S., Jozsi, M., Neumann, H. P. H., Remuzzi, G., Zipfel, P. F. &lt;strong&gt;Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome.&lt;/strong&gt; J. Clin. Invest. 111: 1181-1190, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12697737/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12697737&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI16651&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12697737">Manuelian et al. (2003)</a> demonstrated that pathogenic mutations in the CFH gene (<a href="/entry/134370#0001">134370.0001</a>; <a href="/entry/134370#0017">134370.0017</a>-<a href="/entry/134370#0018">134370.0018</a>) resulted in mutant proteins with decreased binding to heparin, C3b/C3d, and human endothelial cells. The findings suggested that reduced interaction with the surface of endothelial cells is central to the pathophysiology of aHUS and that normal factor H has a protective role during tissue injury. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12697737" 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="#49" class="mim-tip-reference" title="Stahl, A., Vaziri-Sani, F., Heinen, S., Kristoffersson, A.-C., Gydell, K.-H., Raafat, R., Gutierrez, A., Beringer, O., Zipfel, P. F., Karpman, D. &lt;strong&gt;Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation.&lt;/strong&gt; Blood 111: 5307-5315, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18268093/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18268093&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2007-08-106153&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18268093">Stahl et al. (2008)</a> demonstrated that aHUS-associated mutant factor H (see, e.g., <a href="/entry/134370#0022">134370.0022</a>) exhibited decreased binding to normal platelets compared to wildtype factor H. Addition of patient serum containing mutant factor H to control platelets resulted in complement activation, deposition of C3 and C9, release of platelet-derived microparticles, and platelet aggregation, indicating platelet activation. Similar findings were obtained with other aHUS-associated CFH mutations. Preincubation of normal platelets with factor H reduced these effects. The findings indicated that mutant CFH results in complement activation on the surface of platelets and platelet activation, which may contribute to thrombocytopenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18268093" 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>Autoantibodies in aHUS</em></strong></p><p>
<a href="#13" class="mim-tip-reference" title="Dragon-Durey, M.-A., Loirat, C., Cloarec, S., Macher, M.-A., Blouin, J., Nivet, H., Weiss, L., Fridman, W. H., Fremeaux-Bacchi, V. &lt;strong&gt;Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome.&lt;/strong&gt; J. Am. Soc. Nephrol. 16: 555-563, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15590760/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15590760&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.2004050380&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15590760">Dragon-Durey et al. (2005)</a> identified serum anti-CFH IgG autoantibodies in 3 (6%) of 48 children with recurrent aHUS. Plasma CFH activity was decreased, whereas plasma CFH antigen levels were normal and CFH gene analysis was normal, indicating an acquired functional CFH deficiency. The findings indicated that aHUS may occur in the context of an autoimmune disease, and suggested that plasma exchange or immunosuppression may be a beneficial treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15590760" 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>Of 147 patients with aHUS, 121 of whom had previously been reported by <a href="#60" class="mim-tip-reference" title="Zipfel, P. F., Edey, M., Heinen, S., Jozsi, M., Richter, H., Misselwitz, J., Hoppe, B., Routledge, D., Strain, L., Hughes, A. E., Goodship, J. A., Licht, C., Goodship, T. H. J., Skerka, C. &lt;strong&gt;Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome.&lt;/strong&gt; PLoS Genet. 3: e41, 2007. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17367211/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17367211&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17367211[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1371/journal.pgen.0030041&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17367211">Zipfel et al. (2007)</a>, <a href="#24" class="mim-tip-reference" title="Jozsi, M., Licht, C., Strobel, S., Zipfel, S. L. H., Richter, H., Heinen, S., Zipfel, P. F., Skerka, C. &lt;strong&gt;Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.&lt;/strong&gt; Blood 111: 1512-1514, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18006700/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18006700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2007-09-109876&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18006700">Jozsi et al. (2008)</a> identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. These observations suggested that CFHR1/CFHR3 deficiency represents a risk factor for CFH autoantibody formation. Unaffected family members with decreased CFHR1/CFHR3 did not have CFH autoantibodies. The binding epitopes of all autoantibodies were localized to the C-terminal recognition region of factor H, which represents a hotspot for aHUS mutations. The authors thus defined a subgroup of aHUS, which they termed DEAP HUS (deficiency of CFHR proteins and CFH autoantibody positive), that is characterized by a combination of genetic and acquired factors. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18006700+17367211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Dragon-Durey, M.-A., Blanc, C., Marliot, F., Loirat, C., Blouin, J., Sautes-Fridman, C., Fridman, W. H., Fremeaux-Bacchi, V. &lt;strong&gt;The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome.&lt;/strong&gt; J. Med. Genet. 46: 447-450, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19435718/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19435718&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2008.064766&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19435718">Dragon-Durey et al. (2009)</a> found a deletion of 1 or both CFHR1/CFHR3 alleles in 22.7% of 144 French aHUS patients and only 8.2% of 70 healthy controls. The highest deletion frequency was in the subgroup of aHUS patients with anti-factor H autoantibodies (92.9% had 1 or 2 deleted alleles) and in the group of patients with a CFI mutation (31.8% had 1 or 2 deleted alleles). Deletion of CFHR1/CFHR3 was not significantly more frequent in those patients in whom anti-CFH antibodies or CFI mutation were excluded. The findings indicated that genomic deletion of CFHR1/CFHR3 plays a role in the development of anti-CFH autoantibodies, but likely has only a secondary role in susceptibility to aHUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19435718" 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>Typical Hemolytic Uremic Syndrome</em></strong></p><p>
<a href="#26" class="mim-tip-reference" title="Kaplan, B. S., Drummond, K. N. &lt;strong&gt;The hemolytic-uremic syndrome is a syndrome. (Editorial)&lt;/strong&gt; New Eng. J. Med. 298: 964-966, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/642978/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;642978&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197804272981710&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="642978">Kaplan and Drummond (1978)</a> noted that typical HUS is triggered by specific infection. Typical HUS follows a prodrome of acute afebrile gastroenteritis, often with bloody stools. HUS and a hitherto poorly recognized condition, haemorrhagic colitis, which is clinically and pathologically similar to the prodromal bloody diarrheal phase of classic HUS, are related in a causal way to verocytotoxin-producing Escherichia coli (VTEC) infection (<a href="#28" class="mim-tip-reference" title="Karmali, M. A., Petric, M., Lim, C., Fleming, P. C., Arbus, G. S., Lior, H. &lt;strong&gt;The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli.&lt;/strong&gt; J. Infect. Dis. 151: 775-782, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3886804/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3886804&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/infdis/151.5.775&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3886804">Karmali et al., 1985</a>). Verocytotoxin refers to the capacity of this family of potent protein exotoxins to produce an irreversible cytopathic effect in certain cultured cell lines, especially Vero and HeLa. The toxin is also lethal to laboratory animals, especially rabbits, in minute doses. E. coli O157:H7, the most frequently isolated serotype of verotoxin-producing E. coli in the United States, is capable of causing a broad spectrum of illness, including nonbloody diarrhea, bloody diarrhea, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura (<a href="#19" class="mim-tip-reference" title="Griffin, P. M., Ostroff, S. M., Tauxe, R. V., Greene, K. D., Wells, J. G., Lewis, J. H., Blake, P. A. &lt;strong&gt;Illnesses associated with Escherichia coli O157:H7 infections: a broad clinical spectrum.&lt;/strong&gt; Ann. Intern. Med. 109: 705-712, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3056169/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3056169&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.7326/0003-4819-109-9-705&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3056169">Griffin et al., 1988</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=642978+3056169+3886804" 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="#43" class="mim-tip-reference" title="Proulx, F., Toledano, B., Phan, V., Clermont, M.-J., Mariscalco, M. M., Seidman, E. G. &lt;strong&gt;Circulating granulocyte colony-stimulating factor, C-X-C, and C-C chemokines in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome.&lt;/strong&gt; Pediat. Res. 52: 928-934, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12438672/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12438672&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-200212000-00019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12438672">Proulx et al. (2002)</a> compared the circulating concentrations of granulocyte colony-stimulating factor (GCSF; <a href="/entry/138970">138970</a>) and several chemokines in the course of E. coli O157:H7 enteritis, hemorrhagic colitis (HC), and HUS. They found that GROA (<a href="/entry/155730">155730</a>), CCL4 (<a href="/entry/182284">182284</a>), and MCP1 (<a href="/entry/158105">158105</a>) are produced whether or not HC or HUS develops. They also found that children with O157:H7-associated HUS may present abnormally increased circulating levels of GCSF and decreased levels of ENA78 (CXCL5; <a href="/entry/600324">600324</a>). The authors concluded that leukocytes may be involved in the pathogenesis of HUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12438672" 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="#18" class="mim-tip-reference" title="Goodship, J., Warwicker, P., Pirson, Y., Nicholls, A., Turnpenny, P., Goodship, T. &lt;strong&gt;Haemolytic uremic syndrome maps to chromosome 1q and is associated with mutations in the complement factor H gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 61 (suppl.): A56 only, 1997."None>Goodship et al. (1997)</a> undertook a candidate gene linkage study in 2 families with autosomal dominant HUS and in 1 family with a pedigree compatible with recessive inheritance or dominant inheritance with partial penetrance. The disease segregated with the region of 1q containing the candidate HF1 gene (CFH; <a href="/entry/134370">134370</a>); maximum lod = 3.94.</p><p><a href="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al. (1998)</a> demonstrated that familial HUS segregated with the chromosome 1q region, bounded by the markers D1S212 and D1S306, containing the factor H gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9551389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<p>In affected members of a large family with autosomal dominant aHUS originally reported by <a href="#14" class="mim-tip-reference" title="Edelsten, A. D., Tuck, S. &lt;strong&gt;Familial haemolytic uraemic syndrome.&lt;/strong&gt; Arch. Dis. Child. 53: 255-256, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/646435/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;646435&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.53.3.255&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="646435">Edelsten and Tuck (1978)</a>, <a href="#18" class="mim-tip-reference" title="Goodship, J., Warwicker, P., Pirson, Y., Nicholls, A., Turnpenny, P., Goodship, T. &lt;strong&gt;Haemolytic uremic syndrome maps to chromosome 1q and is associated with mutations in the complement factor H gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 61 (suppl.): A56 only, 1997."None>Goodship et al. (1997)</a> and <a href="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al. (1998)</a> identified a heterozygous mutation in the CFH gene (<a href="/entry/134370#0001">134370.0001</a>). Although none of the patients had decreased levels of plasma factor H, <a href="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al. (1998)</a> postulated that the mutation disrupted the structure and function of the protein. In an adult with sporadic HUS, <a href="#57" class="mim-tip-reference" title="Warwicker, P., Goodship, T. H. J., Donne, R. L., Pirson, Y., Nicholls, A., Ward, R. M., Turnpenny, P., Goodship, J. A. &lt;strong&gt;Genetic studies into inherited and sporadic hemolytic uremic syndrome.&lt;/strong&gt; Kidney Int. 53: 836-844, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9551389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9551389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1523-1755.1998.00824.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9551389">Warwicker et al. (1998)</a> identified a heterozygous 4-bp deletion in the HF1 gene (<a href="/entry/134370#0011">134370.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9551389+646435" 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 affected members of a Bedouin kindred with atypical HUS and factor H deficiency originally reported by <a href="#40" class="mim-tip-reference" title="Ohali, M., Shalev, H., Schlesinger, M., Katz, Y., Kachko, L., Carmi, R., Sofer, S., Landau, D. &lt;strong&gt;Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H.&lt;/strong&gt; Pediat. Nephrol. 12: 619-624, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9811382/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9811382&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004670050515&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9811382">Ohali et al. (1998)</a>, <a href="#58" class="mim-tip-reference" title="Ying, L., Katz, Y., Schlesinger, M., Carmi, R., Shalev, H., Haider, N., Beck, G., Sheffield, V. C., Landau, D. &lt;strong&gt;Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 65: 1538-1546, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10577907/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10577907&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10577907[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302673&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10577907">Ying et al. (1999)</a> identified a homozygous mutation in the CFH gene (<a href="/entry/134370#0004">134370.0004</a>). In this same family, <a href="#4" class="mim-tip-reference" title="Buddles, M. R. H., Donne, R. L., Richards, A., Goodship, J., Goodship, T. H. J. &lt;strong&gt;Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 66: 1721-1722, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10762557/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10762557&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302877&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10762557">Buddles et al. (2000)</a> identified a different homozygous pathogenic mutation in the CFH gene (<a href="/entry/134370#0005">134370.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10762557+10577907+9811382" 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 2 children from Turkey with relapsing HUS originally reported by <a href="#48" class="mim-tip-reference" title="Rougier, N., Kazatchkine, M. D., Rougier, J.-P., Fremeaux-Bacchi, V., Blouin, J., Deschenes, G., Soto, B., Baudouin, V., Pautard, B., Proesmans, W., Weiss, E., Weiss, L. &lt;strong&gt;Human complement factor H deficiency associated with hemolytic uremic syndrome.&lt;/strong&gt; J. Am. Soc. Nephrol. 9: 2318-2326, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9848786/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9848786&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.V9122318&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9848786">Rougier et al. (1998)</a>, <a href="#12" class="mim-tip-reference" title="Dragon-Durey, M.-A., Fremeaux-Bacchi, V., Loirat, C., Blouin, J., Niaudet, P., Deschenes, G., Coppo, P., Fridman, W. H., Weiss, L. &lt;strong&gt;Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.&lt;/strong&gt; J. Am. Soc. Nephrol. 15: 787-795, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14978182/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14978182&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/01.asn.0000115702.28859.a7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14978182">Dragon-Durey et al. (2004)</a> identified a homozygous mutation in the CFH gene (<a href="/entry/134370#0012">134370.0012</a>). <a href="#12" class="mim-tip-reference" title="Dragon-Durey, M.-A., Fremeaux-Bacchi, V., Loirat, C., Blouin, J., Niaudet, P., Deschenes, G., Coppo, P., Fridman, W. H., Weiss, L. &lt;strong&gt;Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.&lt;/strong&gt; J. Am. Soc. Nephrol. 15: 787-795, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14978182/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14978182&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/01.asn.0000115702.28859.a7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14978182">Dragon-Durey et al. (2004)</a> also identified heterozygous mutations in the CFH gene in 2 additional patients with atypical HUS reported by <a href="#48" class="mim-tip-reference" title="Rougier, N., Kazatchkine, M. D., Rougier, J.-P., Fremeaux-Bacchi, V., Blouin, J., Deschenes, G., Soto, B., Baudouin, V., Pautard, B., Proesmans, W., Weiss, E., Weiss, L. &lt;strong&gt;Human complement factor H deficiency associated with hemolytic uremic syndrome.&lt;/strong&gt; J. Am. Soc. Nephrol. 9: 2318-2326, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9848786/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9848786&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1681/ASN.V9122318&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9848786">Rougier et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9848786+14978182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Caprioli, J., Castelletti, F., Bucchioni, S., Bettinaglio, P., Bresin, E., Pianetti, G., Gamba, S., Brioschi, S., Daina, E., Remuzzi, G., Noris, M. &lt;strong&gt;Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease.&lt;/strong&gt; Hum. Molec. Genet. 12: 3385-3395, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14583443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14583443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddg363&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14583443">Caprioli et al. (2003)</a> analyzed the complete HF1 gene in 101 patients with HUS, 32 patients with TTP, and 106 controls in order to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and nonmutation carriers, and the role of HF1 polymorphisms in the predisposition to HUS. They found 17 different HF1 mutations (16 heterozygous and 1 homozygous) in 33 HUS patients; 13 mutations were located in exons 22 and 23. No TTP patient carried HF1 mutations. HUS manifested earlier and the mortality rate was higher in mutation carriers than in noncarriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in patients without HF1 mutations half of the grafts were functioning after 1 year. Three HF1 polymorphisms were strongly associated with aHUS: a -257T promoter allele, a 2089G allele in exon 14, and a 2881T allele in exon 19, resulting in an glu963-to-asp substitution. Two or 3 disease-associated variants led to a higher risk of HUS than 1 alone. Analysis of available relatives of mutation patients revealed a penetrance of 50%. In 5 of 9 families the proband inherited the mutation from 1 parent and 2 disease-associated variants from the other, while unaffected carriers inherited the protective variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583443" 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="#7" class="mim-tip-reference" title="Caprioli, J., Noris, M., Brioschi, S., Pianetti, G., Castelletti, F., Bettinaglio, P., Mele, C., Bresin, E., Cassis, L., Gamba, S., Porrati, F., Bucchioni, S., Monteferrante, F., Fang, C. J., Liszewski, M. K., Kavanagh, D., Atkinson, J. P., Remuzzi, G. &lt;strong&gt;Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.&lt;/strong&gt; Blood 108: 1267-1279, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16621965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16621965&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16621965[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2005-10-007252&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16621965">Caprioli et al. (2006)</a> identified mutations in the CFH gene in 47 (30%) of 156 patients with aHUS. Most were heterozygous, but some families had homozygous mutations. Most of the mutations were spread over the 5 exons that encode the most C-terminal part of CFH, often clustering in SCR20, which is involved in binding to surface-bound C3b. In a comparison of 14 aHUS patients with MCP mutations and 42 with CFH mutations, <a href="#7" class="mim-tip-reference" title="Caprioli, J., Noris, M., Brioschi, S., Pianetti, G., Castelletti, F., Bettinaglio, P., Mele, C., Bresin, E., Cassis, L., Gamba, S., Porrati, F., Bucchioni, S., Monteferrante, F., Fang, C. J., Liszewski, M. K., Kavanagh, D., Atkinson, J. P., Remuzzi, G. &lt;strong&gt;Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.&lt;/strong&gt; Blood 108: 1267-1279, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16621965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16621965&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16621965[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2005-10-007252&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16621965">Caprioli et al. (2006)</a> found that patients with MCP mutations had an overall better prognosis. Complete remission was observed in 85.7% of patients with MCP mutations compared to 17.5% of patients with CFH mutations. Only 1 patient with an MCP mutation developed end-stage renal failure and none died during the acute episode, whereas end-stage renal failure and death occurred in 22% and 30%, respectively, of patients with CFH mutations. Most (85%) of the patients with MCP mutations retained normal renal function compared to 22.5% of patients with CFH mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16621965" 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>Modifier Genes</em></strong></p><p>
<a href="#60" class="mim-tip-reference" title="Zipfel, P. F., Edey, M., Heinen, S., Jozsi, M., Richter, H., Misselwitz, J., Hoppe, B., Routledge, D., Strain, L., Hughes, A. E., Goodship, J. A., Licht, C., Goodship, T. H. J., Skerka, C. &lt;strong&gt;Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome.&lt;/strong&gt; PLoS Genet. 3: e41, 2007. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17367211/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17367211&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17367211[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1371/journal.pgen.0030041&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17367211">Zipfel et al. (2007)</a> found that an 84-kb deletion of the CFHR1 (<a href="/entry/134371#0001">134371.0001</a>) and CFHR3 (<a href="/entry/605336#0001">605336.0001</a>) genes was associated with an increased risk of atypical hemolytic-uremic syndrome in 2 independent European cohorts. In the first group, 19 (16%) of 121 aHUS patients had the deletion compared to 2 of 100 control individuals. Three of the patients had a homozygous deletion. All patients had normal serum factor H levels. In the second group comprising 66 patients, 28% had the deletion compared to 6% of controls. Ten percent and 2% of patients and controls, respectively, were homozygous for the deletion. In vitro functional expression studies showed that CFHR1/CFHR3-deficient plasma had decreased protective activity against erythrocyte lysis, suggesting a defective regulation of complement activation. Of 147 patients with aHUS, 121 of whom had previously been reported by <a href="#60" class="mim-tip-reference" title="Zipfel, P. F., Edey, M., Heinen, S., Jozsi, M., Richter, H., Misselwitz, J., Hoppe, B., Routledge, D., Strain, L., Hughes, A. E., Goodship, J. A., Licht, C., Goodship, T. H. J., Skerka, C. &lt;strong&gt;Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome.&lt;/strong&gt; PLoS Genet. 3: e41, 2007. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17367211/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17367211&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17367211[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1371/journal.pgen.0030041&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17367211">Zipfel et al. (2007)</a>, <a href="#24" class="mim-tip-reference" title="Jozsi, M., Licht, C., Strobel, S., Zipfel, S. L. H., Richter, H., Heinen, S., Zipfel, P. F., Skerka, C. &lt;strong&gt;Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.&lt;/strong&gt; Blood 111: 1512-1514, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18006700/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18006700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood-2007-09-109876&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18006700">Jozsi et al. (2008)</a> identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18006700+17367211" 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="Blom, A. M., Bergstrom, F., Edey, M., Diaz-Torres, M., Kavanagh, D., Lampe, A., Goodship, J. A., Strain, L., Moghal, N., McHugh, M., Inward, C., Tomson, C., Fremeaux-Bacchi, V., Villoutreix, B. O., Goodship, T. H. J. &lt;strong&gt;A novel non-synonymous polymorphism (p.arg240his) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity.&lt;/strong&gt; J. Immun. 180: 6385-6391, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18424762/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18424762&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.4049/jimmunol.180.9.6385&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18424762">Blom et al. (2008)</a> identified an arg240-to-his (R240H) SNP in the C4BPA gene (<a href="/entry/120830">120830</a>) that was associated with aHUS. The heterozygous change was found in 6 of 166 patients with aHUS and in 5 of 542 healthy controls. Three of the 6 patients with this SNP carried mutations in other known aHUS susceptibility genes, including MCP and CFH. The findings were replicated in another sample. Functional expression studies showed that the C4BPA variant had impaired ability to bind C3b and to act as a cofactor in its degradation. The findings supported the hypothesis that dysregulation of the alternative complement pathway can lead to aHUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18424762" 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>Associations Pending Confirmation</em></strong></p><p>
For discussion of a possible relationship between variation in the CFHR5 gene and atypical hemolytic uremic syndrome, see <a href="/entry/608593#0003">608593.0003</a>-<a href="/entry/608593#0005">608593.0005</a>.</p>
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<strong>Population Genetics</strong>
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<p><strong><em>Typical Hemolytic Uremic Syndrome</em></strong></p><p>
<a href="#17" class="mim-tip-reference" title="Gianantonio, C. A., Vitacco, M., Mendilaharzu, F., Gallo, G. &lt;strong&gt;The hemolytic-uremic syndrome. Renal status of 76 patients at long-term follow-up.&lt;/strong&gt; J. Pediat. 72: 757-765, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5652602/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5652602&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(68)80427-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5652602">Gianantonio et al. (1968)</a> observed 75 cases of HUS in Argentina, where the disorder seems unusually frequent, and assembled some evidence for viral etiology. Endemic areas included Argentina, South Africa, the west coast of the United States, and the Netherlands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5652602" 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="#51" class="mim-tip-reference" title="Tarr, P. I., Neill, M. A., Allen, J., Siccardi, C. J., Watkins, S. L., Hickman, R. O. &lt;strong&gt;The increasing incidence of the hemolytic-uremic syndrome in King County, Washington: lack of evidence for ascertainment bias.&lt;/strong&gt; Am. J. Epidemiol. 129: 582-586, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2916551/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2916551&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/oxfordjournals.aje.a115170&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2916551">Tarr et al. (1989)</a> reported an increase in the incidence of HUS in King County, Washington, during the previous 15 years. In Minnesota, <a href="#33" class="mim-tip-reference" title="Martin, D. L., MacDonald, K. L., White, K. E., Soler, J. T., Osterholm, M. T. &lt;strong&gt;The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota.&lt;/strong&gt; New Eng. J. Med. 323: 1161-1167, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2215593/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2215593&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199010253231703&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2215593">Martin et al. (1990)</a> reported an increase in mean annual incidence from 0.5 case per 100,000 child-years among children less than 18 in 1979 to 2.0 cases per 100,000 in 1988 (P = 0.000004). Of 28 patients, 13 (46%) showed E. coli O157:H7 in stool specimens. Patients were more likely than controls to attend large day-care centers, suggesting that such attendance is a risk factor for HUS. On the basis of the population-attributable risk, however, this factor could account for no more than 16% of the cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2916551+2215593" 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="#45" class="mim-tip-reference" title="Remuzzi, G., Marchesi, D., Misiani, R., Mecca, G., de Gaetano, G., Donati, M. B. &lt;strong&gt;Familial deficiency of a plasma factor stimulating vascular prostacyclin activity.&lt;/strong&gt; Thromb. Res. 16: 517-525, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/390760/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;390760&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0049-3848(79)90098-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="390760">Remuzzi et al. (1979)</a> suggested that deficiency of a vascular prostacyclin stimulator may underlie the disorder. Plasma from a 54-year-old woman with HUS had a low capacity to stimulate PGI2 production by rat aortic rings. Plasma treatment restored this activity. PGI2-stimulating activity was normal in 2 daughters of the proband but consistently low (20-50% of control) in both of her sons, neither of whom had a history or clinical signs of a microangiopathic disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=390760" 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="#Bergstein1974" class="mim-tip-reference" title="Bergstein, J., Michael, A., Jr., Kjellstrand, C., Simmons, R., Najarian, J. &lt;strong&gt;Hemolytic-uremic syndrome in adult sisters.&lt;/strong&gt; Transplantation 17: 487-490, 1974.">Bergstein et al. (1974)</a>; <a href="#Carreras1983" class="mim-tip-reference" title="Carreras, L., Caralps, A., Martinez Amenos, A., Rama, H., Alsina, J. &lt;strong&gt;Hereditary hemolytic uremic syndrome. (Letter)&lt;/strong&gt; Nephron 34: 269, 1983.">Carreras et al. (1983)</a>; <a href="#Carreras1981" class="mim-tip-reference" title="Carreras, L., Romero, R., Requesens, C., Oliver, A. J., Carrera, M., Clavo, M., Alsina, J. &lt;strong&gt;Familial hypocomplementemic hemolytic uremic syndrome with HLA-A3,B7 haplotype.&lt;/strong&gt; JAMA 245: 602-604, 1981.">Carreras et al.
(1981)</a>; <a href="#Hellman1980" class="mim-tip-reference" title="Hellman, R. M., Jackson, D. V., Buss, D. H. &lt;strong&gt;Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome in HLA-identical siblings.&lt;/strong&gt; Ann. Intern. Med. 93: 283-284, 1980.">Hellman et al. (1980)</a>; <a href="#Hymes1981" class="mim-tip-reference" title="Hymes, L. C., Warshaw, B. L. &lt;strong&gt;Hemolytic-uremic syndrome in two siblings from a nonendemic area.&lt;/strong&gt; Am. J. Dis. Child. 135: 766-767, 1981.">Hymes and Warshaw (1981)</a>; <a href="#Karlsberg1977" class="mim-tip-reference" title="Karlsberg, R. P., Lacher, J. W., Bartecchi, C. E. &lt;strong&gt;Adult hemolytic-uremic syndrome: familial variant.&lt;/strong&gt; Arch. Intern. Med. 137: 1155-1157, 1977.">Karlsberg et
al. (1977)</a>; <a href="#Koster1978" class="mim-tip-reference" title="Koster, F., Levin, J., Walker, L., Tung, K. S. K., Gilman, R. H., Rahaman, M., Majid, A., Islam, S., Williams, R. C., Jr. &lt;strong&gt;Hemolytic-uremic syndrome after shigellosis: relation to endotoxemia and circulating immune complexes.&lt;/strong&gt; New Eng. J. Med. 298: 927-933, 1978.">Koster et al. (1978)</a>; <a href="#Tune1974" class="mim-tip-reference" title="Tune, B. M. &lt;strong&gt;Hemolytic-uremic syndrome in siblings--prospective survey.&lt;/strong&gt; J. Pediat. 85: 682-683, 1974.">Tune (1974)</a>; <a href="#Wallace1975" class="mim-tip-reference" title="Wallace, D. C., Lovric, A., Clubb, J. S., Carseldine, D. B. &lt;strong&gt;Thrombotic thrombocytopenic purpura in four siblings.&lt;/strong&gt; Am. J. Med. 58: 724-734, 1975.">Wallace et al. (1975)</a>
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Bergstein, J., Michael, A., Jr., Kjellstrand, C., Simmons, R., Najarian, J.
<strong>Hemolytic-uremic syndrome in adult sisters.</strong>
Transplantation 17: 487-490, 1974.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4597177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4597177</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4597177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00007890-197405000-00007" target="_blank">Full Text</a>]
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<a id="Blattler1975" class="mim-anchor"></a>
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Blattler, W., Wegmann, W., Herold, H., Straub, P. W.
<strong>Familiaeres haemolytisch-uraemisches Syndrom: Untersuchungen zur Pathogenesis bei den Ueberlebenden.</strong>
Schweiz. Med. Wschr. 105: 1773-1774, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1215973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1215973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1215973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Blom2008" class="mim-anchor"></a>
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Blom, A. M., Bergstrom, F., Edey, M., Diaz-Torres, M., Kavanagh, D., Lampe, A., Goodship, J. A., Strain, L., Moghal, N., McHugh, M., Inward, C., Tomson, C., Fremeaux-Bacchi, V., Villoutreix, B. O., Goodship, T. H. J.
<strong>A novel non-synonymous polymorphism (p.arg240his) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity.</strong>
J. Immun. 180: 6385-6391, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18424762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18424762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18424762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.4049/jimmunol.180.9.6385" target="_blank">Full Text</a>]
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Buddles, M. R. H., Donne, R. L., Richards, A., Goodship, J., Goodship, T. H. J.
<strong>Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. (Letter)</strong>
Am. J. Hum. Genet. 66: 1721-1722, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762557</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10762557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302877" target="_blank">Full Text</a>]
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<a id="Campbell1965" class="mim-anchor"></a>
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Campbell, S., Carre, I. J.
<strong>Fatal haemolytic uraemic syndrome and idiopathic hyperlipaemia in monozygotic twins.</strong>
Arch. Dis. Child. 40: 654-658, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5844955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5844955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5844955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.40.214.654" target="_blank">Full Text</a>]
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<a id="Caprioli2003" class="mim-anchor"></a>
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Caprioli, J., Castelletti, F., Bucchioni, S., Bettinaglio, P., Bresin, E., Pianetti, G., Gamba, S., Brioschi, S., Daina, E., Remuzzi, G., Noris, M.
<strong>Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease.</strong>
Hum. Molec. Genet. 12: 3385-3395, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14583443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14583443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddg363" target="_blank">Full Text</a>]
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<a id="Caprioli2006" class="mim-anchor"></a>
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Caprioli, J., Noris, M., Brioschi, S., Pianetti, G., Castelletti, F., Bettinaglio, P., Mele, C., Bresin, E., Cassis, L., Gamba, S., Porrati, F., Bucchioni, S., Monteferrante, F., Fang, C. J., Liszewski, M. K., Kavanagh, D., Atkinson, J. P., Remuzzi, G.
<strong>Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.</strong>
Blood 108: 1267-1279, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16621965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16621965</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16621965[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=16621965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1182/blood-2005-10-007252" target="_blank">Full Text</a>]
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<a id="Carreras1983" class="mim-anchor"></a>
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Carreras, L., Caralps, A., Martinez Amenos, A., Rama, H., Alsina, J.
<strong>Hereditary hemolytic uremic syndrome. (Letter)</strong>
Nephron 34: 269, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6877464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6877464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6877464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000183028" target="_blank">Full Text</a>]
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<a id="Carreras1981" class="mim-anchor"></a>
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Carreras, L., Romero, R., Requesens, C., Oliver, A. J., Carrera, M., Clavo, M., Alsina, J.
<strong>Familial hypocomplementemic hemolytic uremic syndrome with HLA-A3,B7 haplotype.</strong>
JAMA 245: 602-604, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7452889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7452889</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7452889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Chan1969" class="mim-anchor"></a>
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Chan, J. C. M., Eleff, M. G., Campbell, R. A.
<strong>The hemolytic-uremic syndrome in nonrelated adopted siblings.</strong>
J. Pediat. 75: 1050-1053, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5352831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5352831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5352831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(69)80346-x" target="_blank">Full Text</a>]
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<a id="Dragon-Durey2009" class="mim-anchor"></a>
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Dragon-Durey, M.-A., Blanc, C., Marliot, F., Loirat, C., Blouin, J., Sautes-Fridman, C., Fridman, W. H., Fremeaux-Bacchi, V.
<strong>The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome.</strong>
J. Med. Genet. 46: 447-450, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19435718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19435718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19435718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2008.064766" target="_blank">Full Text</a>]
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<a id="Dragon-Durey2004" class="mim-anchor"></a>
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Dragon-Durey, M.-A., Fremeaux-Bacchi, V., Loirat, C., Blouin, J., Niaudet, P., Deschenes, G., Coppo, P., Fridman, W. H., Weiss, L.
<strong>Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.</strong>
J. Am. Soc. Nephrol. 15: 787-795, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14978182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14978182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14978182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/01.asn.0000115702.28859.a7" target="_blank">Full Text</a>]
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<div class="">
<p class="mim-text-font">
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[<a href="https://doi.org/10.1681/ASN.2004050380" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/adc.53.3.255" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM199811263392202" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(68)80427-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.7326/0003-4819-109-9-705" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM196707202770306" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF02075759" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.7326/0003-4819-93-2-284" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archpedi.1981.02130320074025" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1182/blood-2007-09-109876" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/infdis/151.5.775" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000182427" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/S0140-6736(03)14742-3" target="_blank">Full Text</a>]
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<a id="Zipfel2007" class="mim-anchor"></a>
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Zipfel, P. F., Edey, M., Heinen, S., Jozsi, M., Richter, H., Misselwitz, J., Hoppe, B., Routledge, D., Strain, L., Hughes, A. E., Goodship, J. A., Licht, C., Goodship, T. H. J., Skerka, C.
<strong>Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome.</strong>
PLoS Genet. 3: e41, 2007. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17367211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17367211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17367211[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=17367211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1371/journal.pgen.0030041" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 11/10/2009
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Cassandra L. Kniffin - updated : 8/31/2009<br>Cassandra L. Kniffin - updated : 7/27/2009<br>Cassandra L. Kniffin - updated : 3/11/2009<br>George E. Tiller - updated : 2/5/2008<br>Cassandra L. Kniffin - updated : 11/26/2007<br>Cassandra L. Kniffin - updated : 7/16/2007<br>Cassandra L. Kniffin - updated : 5/1/2007<br>Cassandra L. Kniffin - updated : 9/28/2006<br>George E. Tiller - updated : 1/10/2006<br>Natalie E. Krasikov - updated : 7/7/2004<br>Cassandra L. Kniffin - updated : 3/8/2004<br>Natalie E. Krasikov - updated : 3/8/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 3/4/2003<br>Victor A. McKusick - updated : 10/11/2002<br>Cassandra L. Kniffin - reorganized : 7/3/2002<br>Ada Hamosh - updated : 4/26/2001<br>Victor A. McKusick - updated : 3/8/2001<br>Wilson H. Y. Lo - updated : 7/7/1999<br>Victor A. McKusick - updated : 2/4/1999<br>Victor A. McKusick - updated : 12/2/1998<br>Victor A. McKusick - updated : 10/23/1997
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Creation Date:
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Victor A. McKusick : 6/3/1986
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alopez : 07/11/2023
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ckniffin : 07/10/2023<br>carol : 03/02/2022<br>carol : 03/01/2022<br>alopez : 09/15/2016<br>carol : 11/21/2013<br>carol : 6/3/2013<br>ckniffin : 6/3/2013<br>alopez : 10/1/2012<br>ckniffin : 9/27/2012<br>ckniffin : 9/12/2012<br>carol : 5/15/2012<br>joanna : 5/14/2012<br>carol : 4/30/2012<br>terry : 3/20/2012<br>carol : 11/28/2011<br>carol : 10/6/2010<br>carol : 10/5/2010<br>carol : 11/11/2009<br>ckniffin : 11/10/2009<br>terry : 10/21/2009<br>wwang : 9/11/2009<br>ckniffin : 8/31/2009<br>carol : 7/30/2009<br>ckniffin : 7/27/2009<br>terry : 6/3/2009<br>wwang : 3/19/2009<br>ckniffin : 3/11/2009<br>joanna : 2/27/2009<br>terry : 2/26/2009<br>carol : 3/19/2008<br>wwang : 2/13/2008<br>terry : 2/5/2008<br>wwang : 12/27/2007<br>ckniffin : 11/26/2007<br>wwang : 7/20/2007<br>ckniffin : 7/16/2007<br>carol : 5/4/2007<br>ckniffin : 5/1/2007<br>carol : 10/5/2006<br>ckniffin : 9/28/2006<br>wwang : 1/20/2006<br>terry : 1/10/2006<br>wwang : 8/3/2005<br>carol : 7/7/2004<br>tkritzer : 4/20/2004<br>ckniffin : 3/8/2004<br>carol : 3/8/2004<br>carol : 3/8/2004<br>ckniffin : 3/5/2004<br>cwells : 2/17/2004<br>terry : 2/9/2004<br>cwells : 3/11/2003<br>terry : 3/4/2003<br>tkritzer : 10/11/2002<br>tkritzer : 10/11/2002<br>carol : 7/3/2002<br>carol : 7/3/2002<br>ckniffin : 7/3/2002<br>alopez : 5/8/2001<br>terry : 4/26/2001<br>terry : 3/26/2001<br>mcapotos : 3/20/2001<br>mcapotos : 3/20/2001<br>mcapotos : 3/20/2001<br>mcapotos : 3/16/2001<br>terry : 3/8/2001<br>alopez : 12/7/1999<br>alopez : 12/6/1999<br>carol : 7/16/1999<br>kayiaros : 7/7/1999<br>carol : 2/6/1999<br>terry : 2/4/1999<br>carol : 12/15/1998<br>carol : 12/7/1998<br>terry : 12/2/1998<br>terry : 10/28/1997<br>terry : 10/24/1997<br>terry : 10/23/1997<br>mark : 3/31/1996<br>terry : 3/21/1996<br>mimadm : 6/8/1994<br>davew : 6/2/1994<br>carol : 3/26/1992<br>supermim : 3/16/1992<br>carol : 3/7/1992<br>carol : 12/10/1990
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<strong>#</strong> 235400
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HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1; AHUS1
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<em>Alternative titles; symbols</em>
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AHUS, SUSCEPTIBILITY TO, 1
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Other entities represented in this entry:
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HEMOLYTIC UREMIC SYNDROME, TYPICAL, INCLUDED
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<strong>ORPHA:</strong> 2134, 544472, 90038, 93581; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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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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<span class="mim-font">
1q31.3
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{Hemolytic uremic syndrome, atypical, susceptibility to, 1}
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235400
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Autosomal dominant; Autosomal recessive
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3
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CFH
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134370
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1q31.3
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<span class="mim-font">
{Hemolytic uremic syndrome, atypical, susceptibility to}
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235400
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Autosomal dominant; Autosomal recessive
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3
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CFHR3
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605336
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1q31.3
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{Hemolytic uremic syndrome, atypical, susceptibility to}
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235400
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Autosomal dominant; Autosomal recessive
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3
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CFHR1
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134371
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-1 (AHUS1) can be conferred by variation in the gene encoding complement factor H (CFH; 134370) on chromosome 1q31.</p><p>Deficiency of the CFH-related proteins CFHR1 (134371) and CFHR3 (605336) may be associated with development of the disorder due to autoantibodies. Other genes may play a role in modifying the phenotype (see MOLECULAR GENETICS).</p><p>HUS can share overlapping clinical features with thrombotic thrombocytopenic purpura (TTP; 274150), which is caused by mutation in the von Willebrand factor-cleaving protease (VWFCP) gene (ADAMTS13; 604134).</p>
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<strong>Description</strong>
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<p>Typical hemolytic uremic syndrome is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes ('burr cells'). The vast majority of cases (90%) are sporadic, occur in children under 3 years of age, and are associated with epidemics of diarrhea caused by verotoxin-producing E. coli. The death rate is very low, about 30% of cases have renal sequelae, and there is usually no relapse of the disease. This form of HUS usually presents with a diarrhea prodrome (thus referred to as D+HUS) and has a good prognosis in most cases. In contrast, a subgroup of patients with HUS have an atypical presentation (aHUS or D-HUS) without a prodrome of enterocolitis and diarrhea and have a much poorer prognosis, with a tendency to relapse and frequent development of end-stage renal failure or death. These cases tend to be familial. Both autosomal recessive and autosomal dominant inheritance have been reported (Goodship et al., 1997; Taylor, 2001; Veyradier et al., 2003; Noris et al., 2003). Noris and Remuzzi (2009) provided a detailed review of atypical HUS. </p><p><strong><em>Genetic Heterogeneity of Atypical Hemolytic Uremic Syndrome</em></strong></p><p>
Atypical HUS is a genetically heterogeneous condition. Susceptibility to the development of the disorder can be conferred by mutations in various components of or regulatory factors in the complement cascade system (Jozsi et al., 2008). See AHUS2 (612922), AHUS3 (612923), AHUS4 (612924), AHUS5 (612925), and AHUS6 (612926). AHUS7 (see 615008) is caused by mutation in the DGKE gene (601440), which is not part of the complement cascade system. AHUS8 (301110) is caused by mutation in the C1GALT1C1 gene (300611), encoding a molecular chaperone with an essential role in mucin-type O-glycan biosynthesis, on chromosome Xq23. </p>
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<strong>Clinical Features</strong>
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<p>Hagge et al. (1967) reported the hemolytic uremic syndrome in 2 sibs. Features included intravascular hemolysis, thrombocytopenia, and azotemia. One had repeated attacks ending in renal failure and death at age 8 years; the other recovered completely after one attack. Chan et al. (1969) reported HUS in 2 adopted, unrelated sibs. </p><p>Kaplan et al. (1975) reported HUS in 3 sibs and reviewed reports of 21 sibships with 2 or more affected individuals. Two groups of families could be identified among 41 analyzed. Sibs whose onset was within a short time of each other had a relatively good prognosis (19% mortality). Those whose onset was more than a year apart had a poorer prognosis (68% mortality). Kaplan et al. (1975) suggested that an environmental agent was causative in the first group and that genetic factors were important in the second. Most of the first group of families came from an endemic area, whereas most of the second group came from a nonendemic area. </p><p>Blattler et al. (1975) studied a family in which 4 sibs had died from HUS. The parents and 4 surviving sibs had normal renal function and normal platelet and fibrinogen survival. The mother and 3 sibs had an increased percentage of megathrombocytes. Two of them showed renal accumulation of Cr 51-platelet radioactivity and ultrastructural changes of the endothelium on renal biopsy. </p><p>Edelsten and Tuck (1978) reported a family with HUS inherited in an autosomal dominant pattern. </p><p>Thompson and Winterborn (1981) reported an 8-month-old Asian boy with very low levels of plasma factor H who presented with the hemolytic uremic syndrome. Complement component C3 (120700) was also depleted. A healthy 3-year-old brother had the same complement profile, suggesting activation of the alternative complement pathway. The parents, who were first cousins, had half-normal levels of factor H. </p><p>Kirchner et al. (1982) described this disorder in mother and daughter. The daughter's illness, characterized primarily by renal insufficiency, was most compatible with adult hemolytic uremic syndrome and the mother's illness, with prominent neurologic findings, was most compatible with thrombotic thrombocytopenic purpura. Merrill et al. (1985) reported 2 certain cases and 3 possible case in 2 generations of a North Carolina black family. </p><p>Neuhaus et al. (1997) reported clinical features of atypical D-HUS in 23 children. Features included requirement for dialysis (74%), hypertension (43%), cardiomyopathy (43%), and cerebral convulsions (48%). Only 5 patients (26%), including 4 infants, recovered completely. Six patients (32%) had 1 to 10 recurrences and 8 (42%) developed end-stage renal failure. Four children died. </p><p>Warwicker et al. (1998) reported a 36-year-old man with sporadic relapsing aHUS. He had anemia, thrombocytopenia, hypertension, and acute renal failure. Renal biopsy showed a thrombotic microangiopathy and deposition of complement component C3 in vessel walls. He had half-normal serum levels of factor H and decreased levels of C3, consistent with activation of the alternative complement pathway. HUS recurred after renal transplantation. Molecular analysis revealed a heterozygous 4-bp deletion in the CFH gene (134370.0011). </p><p>Ohali et al. (1998) reported a large consanguineous Bedouin family in which 10 infants had atypical HUS characterized by microangiopathic hemolytic anemia, acute renal failure, severe hypertension, edema, and increased serum triglycerides. All had very early onset with a median presentation at age 2 weeks. Two patients died during the first disease episode; the remaining 8 patients had a mean number of 4 relapses despite treatment. In total, 8 patients died at ages 3 weeks to 10 months. Factor H levels were low to undetectable in all 4 patients studied, and C3 levels were decreased in 9 of 10 infants tested. Four kidney biopsies showed marked arteriolar changes, including stenosis, edema, and thickening of the intima. Glomerular changes included swelling of endothelial cells with microvillus transformation and proliferation of mesangial cells with increased matrix deposition in the mesangium. Other changes included fibrotic changes in glomeruli and the tubulointerstitium, as well as C3 deposition in capillary walls. </p><p>Rougier et al. (1998) reported 6 children with complement factor H deficiency and acute glomerular disease. Five of the 6 children presented with hemolytic uremic syndrome. Two of the children were from a consanguineous family from Turkey and exhibited a homozygous deficiency characterized by absence of the 150-kD form of factor H. </p><p>Noris et al. (2003) reported a 21-year-old woman and her affected brother. Disease onset in the sister (the proband) was at age 16 months, when she developed fever, hemolytic anemia, and thrombocytopenia. At the time, renal function was normal. Thereafter she had 6 recurrences of thrombotic microangiopathy, all associated with deteriorating renal function. Treatment consisted of plasma exchange and infusions, steroids, and blood transfusions, which led to complete recovery of blood abnormalities and renal function. The last episode occurred at age 20 years and was characterized by anemia, thrombocytopenia, and severe impairment of renal function. Renal biopsy showed irreversible changes of chronic nephropathy with typical features of HUS, including diffuse narrowing/occlusion of vessels and severe glomerular ischemia. At the age of 21 years she was on chronic dialysis. The proband's brother had 2 episodes of HUS at age 9 years. Both were characterized by severe hemolytic anemia and acute renal insufficiency and resolved without plasma treatment, with no renal sequelae. </p>
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<strong>Clinical Management</strong>
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<p>Hazani et al. (1996) reported relapsing thrombotic microangiopathy in a 12-year-old girl and her 7-year-old brother. During 11 years of follow-up, the girl responded only to steroids; many other therapeutic modalities were ineffective. Following treatment with low-dose danazol, relapses became fewer and less severe, completely subsiding after 6 months. The brother's illness began with signs of hemolytic uremic syndrome, with later development of neurologic manifestations. During a 6-year follow-up he responded only to plasma exchange. Although chronic thrombocytopenia persisted during the last 3 years, the boy's clinical condition improved. </p><p>Landau et al. (2001) described 2 patients with atypical HUS associated with factor H deficiency. One patient who underwent renal transplantation for end-stage renal disease later had an extensive nonhemorrhagic cerebral infarction on 2 occasions and died in spite of multiple plasma transfusions. A second patient, a 14-month-old boy, experienced numerous HUS episodes starting at the age of 2 weeks. Daily plasma transfusions during relapses brought about only a temporary state of remission. However, prophylactic twice-weekly plasma therapy had been successful in preventing relapses and preserving renal function. Landau et al. (2001) reported that with this regimen, serum factor H was increased from 6 mg/dL to subnormal values of 12 to 25 mg/dL (normal, greater than 60 mg/dL). Landau et al. (2001) concluded that aHUS recurs because factor H deficiency is not corrected by renal transplantation. A hypertransfusion protocol may be useful. </p>
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<strong>Inheritance</strong>
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<p>Concordant monozygotic twins have been reported (Campbell and Carre, 1965). Farr et al. (1975) described a family with several affected members, including a father and his son and daughter. A common symptom was hypertension. They reviewed reports of familial occurrence. Perret et al. (1979) described this disorder in 5 members of 3 generations of a kindred and suggested genetic predisposition with a dominant gene. </p><p>In the study by Furlan et al. (1998), there were multiple patients with the familial form of HUS: patients 44 and 45 were sister and brother and had 8 sibs who had died of acute HUS; patient 46 (a male) had 3 brothers who had died of HUS; from 2 other unrelated families, patients 47 and 48 were sisters and patients 49 and 50 were brothers; 1 brother and 1 sister of patient 51 had died of HUS; patients 52 and 53 were brother and sister. </p><p>Goodship et al. (1997) stated that most familial cases are recessive but dominant pedigrees had also been reported.</p><p>In a review of thrombotic microangiopathies, Moake (2002) stated that 5 to 10% of cases of HUS are familial. The mortality rate (54%) is much higher in the familial form than in typical childhood HUS (3 to 5%). About half of the survivors have relapses and over one-third require long-term dialysis. Among patients with familial HUS who receive kidney allografts, 16% lose function in the engrafted kidney within 1 month. </p>
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<strong>Pathogenesis</strong>
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<p><strong><em>Atypical Hemolytic Uremic Syndrome</em></strong></p><p>
Low levels of factor H in patients with aHUS were reported by Roodhooft et al. (1990), Pichette et al. (1994), and others. Some patients, however, may have normal levels of factor H, suggesting a dysfunction of the protein (Warwicker et al., 1998). </p><p>Reduced serum C3 levels have been reported in sporadic (Stuhlinger et al., 1974; Robson et al., 1992) and familial HUS (Zachwieja et al., 1992). In Italy, Noris et al. (1999) studied 6 families with HUS, 1 family with TTP, and 2 families with both disorders. Included in the study were 15 patients and 63 available healthy relatives as well as 25 age- and gender-matched healthy controls and 56 of their available relatives. Consanguinity was observed in 2 families. Seventy-three percent of the cases versus 16% of controls (P less than 0.001) as well as 24% of case-relatives versus 5% of control-relatives (P = 0.005) had decreased C3 levels, which were more marked in the actual cases. Factor H abnormalities were found in 4 of the 15 cases as compared with 3 of the 63 case-relatives and none of 17 healthy controls. All cases with factor H abnormalities had low C3 serum concentrations. Noris et al. (1999) concluded that reduced C3 in familial HUS is likely related to a genetically determined deficiency of factor H. </p><p>Remuzzi et al. (2002) concluded that ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and that it is not the only determinant of VWF (613160) abnormalities in these conditions. </p><p>In 41 children with D+HUS and 23 children with D-HUS, Veyradier et al. (2003) found that von Willebrand factor-cleaving protease activity was normal in over 50% of patients, but was undetectable in 1 D+HUS and 6 D-HUS children. After a 3-month remission, the D+HUS patient recovered 100% VWFCP activity, whereas the 6 D-HUS patients kept an undetectable level. In these 6 D-HUS patients, the disease was characterized by a neonatal onset and several relapses of hemolytic anemia, thrombocytopenia, acute renal failure, and cerebral ischemia. Arterial hypertension and end-stage renal failure sometimes occurred. Veyradier et al. (2003) concluded that a subgroup of patients with D-HUS is related to VWFCP and may actually correspond to TTP. </p><p>Using in vitro expression studies, Manuelian et al. (2003) demonstrated that pathogenic mutations in the CFH gene (134370.0001; 134370.0017-134370.0018) resulted in mutant proteins with decreased binding to heparin, C3b/C3d, and human endothelial cells. The findings suggested that reduced interaction with the surface of endothelial cells is central to the pathophysiology of aHUS and that normal factor H has a protective role during tissue injury. </p><p>Stahl et al. (2008) demonstrated that aHUS-associated mutant factor H (see, e.g., 134370.0022) exhibited decreased binding to normal platelets compared to wildtype factor H. Addition of patient serum containing mutant factor H to control platelets resulted in complement activation, deposition of C3 and C9, release of platelet-derived microparticles, and platelet aggregation, indicating platelet activation. Similar findings were obtained with other aHUS-associated CFH mutations. Preincubation of normal platelets with factor H reduced these effects. The findings indicated that mutant CFH results in complement activation on the surface of platelets and platelet activation, which may contribute to thrombocytopenia. </p><p><strong><em>Autoantibodies in aHUS</em></strong></p><p>
Dragon-Durey et al. (2005) identified serum anti-CFH IgG autoantibodies in 3 (6%) of 48 children with recurrent aHUS. Plasma CFH activity was decreased, whereas plasma CFH antigen levels were normal and CFH gene analysis was normal, indicating an acquired functional CFH deficiency. The findings indicated that aHUS may occur in the context of an autoimmune disease, and suggested that plasma exchange or immunosuppression may be a beneficial treatment. </p><p>Of 147 patients with aHUS, 121 of whom had previously been reported by Zipfel et al. (2007), Jozsi et al. (2008) identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. These observations suggested that CFHR1/CFHR3 deficiency represents a risk factor for CFH autoantibody formation. Unaffected family members with decreased CFHR1/CFHR3 did not have CFH autoantibodies. The binding epitopes of all autoantibodies were localized to the C-terminal recognition region of factor H, which represents a hotspot for aHUS mutations. The authors thus defined a subgroup of aHUS, which they termed DEAP HUS (deficiency of CFHR proteins and CFH autoantibody positive), that is characterized by a combination of genetic and acquired factors. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. </p><p>Dragon-Durey et al. (2009) found a deletion of 1 or both CFHR1/CFHR3 alleles in 22.7% of 144 French aHUS patients and only 8.2% of 70 healthy controls. The highest deletion frequency was in the subgroup of aHUS patients with anti-factor H autoantibodies (92.9% had 1 or 2 deleted alleles) and in the group of patients with a CFI mutation (31.8% had 1 or 2 deleted alleles). Deletion of CFHR1/CFHR3 was not significantly more frequent in those patients in whom anti-CFH antibodies or CFI mutation were excluded. The findings indicated that genomic deletion of CFHR1/CFHR3 plays a role in the development of anti-CFH autoantibodies, but likely has only a secondary role in susceptibility to aHUS. </p><p><strong><em>Typical Hemolytic Uremic Syndrome</em></strong></p><p>
Kaplan and Drummond (1978) noted that typical HUS is triggered by specific infection. Typical HUS follows a prodrome of acute afebrile gastroenteritis, often with bloody stools. HUS and a hitherto poorly recognized condition, haemorrhagic colitis, which is clinically and pathologically similar to the prodromal bloody diarrheal phase of classic HUS, are related in a causal way to verocytotoxin-producing Escherichia coli (VTEC) infection (Karmali et al., 1985). Verocytotoxin refers to the capacity of this family of potent protein exotoxins to produce an irreversible cytopathic effect in certain cultured cell lines, especially Vero and HeLa. The toxin is also lethal to laboratory animals, especially rabbits, in minute doses. E. coli O157:H7, the most frequently isolated serotype of verotoxin-producing E. coli in the United States, is capable of causing a broad spectrum of illness, including nonbloody diarrhea, bloody diarrhea, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura (Griffin et al., 1988). </p><p>Proulx et al. (2002) compared the circulating concentrations of granulocyte colony-stimulating factor (GCSF; 138970) and several chemokines in the course of E. coli O157:H7 enteritis, hemorrhagic colitis (HC), and HUS. They found that GROA (155730), CCL4 (182284), and MCP1 (158105) are produced whether or not HC or HUS develops. They also found that children with O157:H7-associated HUS may present abnormally increased circulating levels of GCSF and decreased levels of ENA78 (CXCL5; 600324). The authors concluded that leukocytes may be involved in the pathogenesis of HUS. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Goodship et al. (1997) undertook a candidate gene linkage study in 2 families with autosomal dominant HUS and in 1 family with a pedigree compatible with recessive inheritance or dominant inheritance with partial penetrance. The disease segregated with the region of 1q containing the candidate HF1 gene (CFH; 134370); maximum lod = 3.94.</p><p>Warwicker et al. (1998) demonstrated that familial HUS segregated with the chromosome 1q region, bounded by the markers D1S212 and D1S306, containing the factor H gene. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In affected members of a large family with autosomal dominant aHUS originally reported by Edelsten and Tuck (1978), Goodship et al. (1997) and Warwicker et al. (1998) identified a heterozygous mutation in the CFH gene (134370.0001). Although none of the patients had decreased levels of plasma factor H, Warwicker et al. (1998) postulated that the mutation disrupted the structure and function of the protein. In an adult with sporadic HUS, Warwicker et al. (1998) identified a heterozygous 4-bp deletion in the HF1 gene (134370.0011). </p><p>In affected members of a Bedouin kindred with atypical HUS and factor H deficiency originally reported by Ohali et al. (1998), Ying et al. (1999) identified a homozygous mutation in the CFH gene (134370.0004). In this same family, Buddles et al. (2000) identified a different homozygous pathogenic mutation in the CFH gene (134370.0005). </p><p>In 2 children from Turkey with relapsing HUS originally reported by Rougier et al. (1998), Dragon-Durey et al. (2004) identified a homozygous mutation in the CFH gene (134370.0012). Dragon-Durey et al. (2004) also identified heterozygous mutations in the CFH gene in 2 additional patients with atypical HUS reported by Rougier et al. (1998). </p><p>Caprioli et al. (2003) analyzed the complete HF1 gene in 101 patients with HUS, 32 patients with TTP, and 106 controls in order to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and nonmutation carriers, and the role of HF1 polymorphisms in the predisposition to HUS. They found 17 different HF1 mutations (16 heterozygous and 1 homozygous) in 33 HUS patients; 13 mutations were located in exons 22 and 23. No TTP patient carried HF1 mutations. HUS manifested earlier and the mortality rate was higher in mutation carriers than in noncarriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in patients without HF1 mutations half of the grafts were functioning after 1 year. Three HF1 polymorphisms were strongly associated with aHUS: a -257T promoter allele, a 2089G allele in exon 14, and a 2881T allele in exon 19, resulting in an glu963-to-asp substitution. Two or 3 disease-associated variants led to a higher risk of HUS than 1 alone. Analysis of available relatives of mutation patients revealed a penetrance of 50%. In 5 of 9 families the proband inherited the mutation from 1 parent and 2 disease-associated variants from the other, while unaffected carriers inherited the protective variants. </p><p>Caprioli et al. (2006) identified mutations in the CFH gene in 47 (30%) of 156 patients with aHUS. Most were heterozygous, but some families had homozygous mutations. Most of the mutations were spread over the 5 exons that encode the most C-terminal part of CFH, often clustering in SCR20, which is involved in binding to surface-bound C3b. In a comparison of 14 aHUS patients with MCP mutations and 42 with CFH mutations, Caprioli et al. (2006) found that patients with MCP mutations had an overall better prognosis. Complete remission was observed in 85.7% of patients with MCP mutations compared to 17.5% of patients with CFH mutations. Only 1 patient with an MCP mutation developed end-stage renal failure and none died during the acute episode, whereas end-stage renal failure and death occurred in 22% and 30%, respectively, of patients with CFH mutations. Most (85%) of the patients with MCP mutations retained normal renal function compared to 22.5% of patients with CFH mutations. </p><p><strong><em>Modifier Genes</em></strong></p><p>
Zipfel et al. (2007) found that an 84-kb deletion of the CFHR1 (134371.0001) and CFHR3 (605336.0001) genes was associated with an increased risk of atypical hemolytic-uremic syndrome in 2 independent European cohorts. In the first group, 19 (16%) of 121 aHUS patients had the deletion compared to 2 of 100 control individuals. Three of the patients had a homozygous deletion. All patients had normal serum factor H levels. In the second group comprising 66 patients, 28% had the deletion compared to 6% of controls. Ten percent and 2% of patients and controls, respectively, were homozygous for the deletion. In vitro functional expression studies showed that CFHR1/CFHR3-deficient plasma had decreased protective activity against erythrocyte lysis, suggesting a defective regulation of complement activation. Of 147 patients with aHUS, 121 of whom had previously been reported by Zipfel et al. (2007), Jozsi et al. (2008) identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. </p><p>Blom et al. (2008) identified an arg240-to-his (R240H) SNP in the C4BPA gene (120830) that was associated with aHUS. The heterozygous change was found in 6 of 166 patients with aHUS and in 5 of 542 healthy controls. Three of the 6 patients with this SNP carried mutations in other known aHUS susceptibility genes, including MCP and CFH. The findings were replicated in another sample. Functional expression studies showed that the C4BPA variant had impaired ability to bind C3b and to act as a cofactor in its degradation. The findings supported the hypothesis that dysregulation of the alternative complement pathway can lead to aHUS. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
For discussion of a possible relationship between variation in the CFHR5 gene and atypical hemolytic uremic syndrome, see 608593.0003-608593.0005.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Typical Hemolytic Uremic Syndrome</em></strong></p><p>
Gianantonio et al. (1968) observed 75 cases of HUS in Argentina, where the disorder seems unusually frequent, and assembled some evidence for viral etiology. Endemic areas included Argentina, South Africa, the west coast of the United States, and the Netherlands. </p><p>Tarr et al. (1989) reported an increase in the incidence of HUS in King County, Washington, during the previous 15 years. In Minnesota, Martin et al. (1990) reported an increase in mean annual incidence from 0.5 case per 100,000 child-years among children less than 18 in 1979 to 2.0 cases per 100,000 in 1988 (P = 0.000004). Of 28 patients, 13 (46%) showed E. coli O157:H7 in stool specimens. Patients were more likely than controls to attend large day-care centers, suggesting that such attendance is a risk factor for HUS. On the basis of the population-attributable risk, however, this factor could account for no more than 16% of the cases. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Remuzzi et al. (1979) suggested that deficiency of a vascular prostacyclin stimulator may underlie the disorder. Plasma from a 54-year-old woman with HUS had a low capacity to stimulate PGI2 production by rat aortic rings. Plasma treatment restored this activity. PGI2-stimulating activity was normal in 2 daughters of the proband but consistently low (20-50% of control) in both of her sons, neither of whom had a history or clinical signs of a microangiopathic disorder. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Bergstein et al. (1974); Carreras et al. (1983); Carreras et al.
(1981); Hellman et al. (1980); Hymes and Warshaw (1981); Karlsberg et
al. (1977); Koster et al. (1978); Tune (1974); Wallace et al. (1975)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
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Dragon-Durey, M.-A., Fremeaux-Bacchi, V., Loirat, C., Blouin, J., Niaudet, P., Deschenes, G., Coppo, P., Fridman, W. H., Weiss, L.
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Dragon-Durey, M.-A., Loirat, C., Cloarec, S., Macher, M.-A., Blouin, J., Nivet, H., Weiss, L., Fridman, W. H., Fremeaux-Bacchi, V.
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Edelsten, A. D., Tuck, S.
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Hymes, L. C., Warshaw, B. L.
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Jozsi, M., Licht, C., Strobel, S., Zipfel, S. L. H., Richter, H., Heinen, S., Zipfel, P. F., Skerka, C.
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</p>
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<li>
<p class="mim-text-font">
Kaplan, B. S., Chesney, R. W., Drummond, K. N.
<strong>Hemolytic uremic syndrome in families.</strong>
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[PubMed: 1128552]
[Full Text: https://doi.org/10.1056/NEJM197505222922102]
</p>
</li>
<li>
<p class="mim-text-font">
Kaplan, B. S., Drummond, K. N.
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[PubMed: 642978]
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<p class="mim-text-font">
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<p class="mim-text-font">
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<strong>The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli.</strong>
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Zipfel, P. F., Edey, M., Heinen, S., Jozsi, M., Richter, H., Misselwitz, J., Hoppe, B., Routledge, D., Strain, L., Hughes, A. E., Goodship, J. A., Licht, C., Goodship, T. H. J., Skerka, C.
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Cassandra L. Kniffin - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 8/31/2009<br>Cassandra L. Kniffin - updated : 7/27/2009<br>Cassandra L. Kniffin - updated : 3/11/2009<br>George E. Tiller - updated : 2/5/2008<br>Cassandra L. Kniffin - updated : 11/26/2007<br>Cassandra L. Kniffin - updated : 7/16/2007<br>Cassandra L. Kniffin - updated : 5/1/2007<br>Cassandra L. Kniffin - updated : 9/28/2006<br>George E. Tiller - updated : 1/10/2006<br>Natalie E. Krasikov - updated : 7/7/2004<br>Cassandra L. Kniffin - updated : 3/8/2004<br>Natalie E. Krasikov - updated : 3/8/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 3/4/2003<br>Victor A. McKusick - updated : 10/11/2002<br>Cassandra L. Kniffin - reorganized : 7/3/2002<br>Ada Hamosh - updated : 4/26/2001<br>Victor A. McKusick - updated : 3/8/2001<br>Wilson H. Y. Lo - updated : 7/7/1999<br>Victor A. McKusick - updated : 2/4/1999<br>Victor A. McKusick - updated : 12/2/1998<br>Victor A. McKusick - updated : 10/23/1997
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