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<input type="hidden" name="email-subject-hash" value="35361252cd2495746a8c32096414df13c77abb05d83454584acf9582880c257c"/>
</div>
<div class="action-panel-control-wrap">
<label for="email-to" class="action-panel-label required-field-asterisk">
To:
</label>
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="dJv6bqIRoMoVZZ1VrjIibxt30oou8EQfuwfbOgbdYnbpTq7L4ClkFFZHys6G1foz">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
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<input type="hidden" name="csrfmiddlewaretoken" value="dJv6bqIRoMoVZZ1VrjIibxt30oou8EQfuwfbOgbdYnbpTq7L4ClkFFZHys6G1foz">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="dJv6bqIRoMoVZZ1VrjIibxt30oou8EQfuwfbOgbdYnbpTq7L4ClkFFZHys6G1foz">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
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<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="dJv6bqIRoMoVZZ1VrjIibxt30oou8EQfuwfbOgbdYnbpTq7L4ClkFFZHys6G1foz">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="23334384">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://dx.doi.org/10.1007/s00467-012-2329-z"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3055&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23334384&amp;db=pubmed&amp;nlmid=8708728"
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"
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target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23334384&amp;db=pubmed&amp;nlmid=8708728"
title="Free full text at PubMed Central"
data-ga-category="full_text"
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<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/23334384/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/23334384/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="23334384" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23334384%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="dJv6bqIRoMoVZZ1VrjIibxt30oou8EQfuwfbOgbdYnbpTq7L4ClkFFZHys6G1foz"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
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Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one"><bold>Conflict of interest statement</bold>: Dr. Goldfarb is a consultant for Takeda.</p>
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<div class="figure-caption-contents"><p> Urinary crystals. A. Typical small… </p></div>
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<div class="figure-caption-contents"><p> Urinary crystals. A. Typical small and medium sized 2,8-dihydroxyadenine crystals. The medium sized… </p></div>
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<div class="figure-caption-contents">Urinary crystals. A. Typical small and medium sized 2,8-dihydroxyadenine crystals. The medium sized cystals are brown with dark outline and central spicules. (Original magnification × 400). B. The same field viewed with polarized light microscopy. The small and medium sized crystals appear yellow in colour and produce a central Maltese cross pattern. (Original magnification × 400). C. Urinary cystine crystals. The typical 6-sided crystal is diagnostic of cystinuria. A good example can be seen on the left side of the Figure (arrow). D. Urinary calcium oxalate crystals. The typical bipyramidal calcium oxalate dihydrate crystals (arrows) and a large dumbbell calcium oxalate monohydrate crystal (asterisk) are both seen. E. Amorphous calcium phosphate crystals. Although their appearance is not as distinctive, amorphous calcium phosphate crystals should be suspected if the urine is alkaline (pH > 6.0).</div>
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<div class="figure-caption-contents"><p> Schematic overview of adenine metabolism.… </p></div>
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<div class="figure-caption-contents"><p> Schematic overview of adenine metabolism. In adenine phosphoribosyltransferase deficiency, adenine cannot be converted… </p></div>
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<div class="figure-caption-contents">Schematic overview of adenine metabolism. In adenine phosphoribosyltransferase deficiency, adenine cannot be converted to adenosine monophsophate and is instead converted by xanthine dehydrogenase to 2,8-dihydroxyadenine. Abbreviations: APRT, adenine phosphoribosyltransferase; AMP, adenosine monophsophate; HPRT, hypoxanthine-guanine phosphoribosyltransferase; IMP, inosine monophosphate; XDH, xanthine dehydrogenase.</div>
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<p> Figure 3 </p>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of… </p></div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadeninuria. Annotations to… </p></div>
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<div class="figure-caption-contents">Algorithm for diagnostic evaluation of adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadeninuria. Annotations to Figure 3 <sup>1</sup>2,8-dihydroxyadeninuria, hyperuricosuria and xanthinuria should always be considered in the differential diagnosis of radiolucent kidney stones in childhood. <sup>2</sup> Children with radiolucent kidney stones and chronic kidney disease (CKD) should be evaluated for adenine phosphoribosyltransferase (APRT) deficiency. <sup>3,6</sup>Patients with APRT deficiency may present with acute kidney injury (AKI), CKD or acute allograft nephropathy, even in the absence of previous history of kidney stones. Kidney biopsy shows variable degree of tubulointerstitial injury and features consistent with crystalline nephropathy. <sup>4</sup>Ultraviolet spectrophotometry and/or x-ray crystallography easily differentiates 2,8-dihydroxyadenine (DHA) from uric acid and xanthine. <sup>5</sup>The pathognomonic round, brown urinary DHA crystals (Figure 1) are seen in almost all patients with the disorder. The crystals may, however, be hard to identify in patients with markedly decreased renal function due to reduced crystal clearance. <sup>7</sup>APRT activity in red blood cell lysates ranges from 16-32 nmol/h/mg hemoglobin in healthy subjects [118]; homozygotes and compound heterozygotes have no measurable enzyme activity and in heterozygotes the activity is approximately 25%. Recent blood transfusion may falsely elevate APRT activity. <sup>8</sup> Genetic testing, which confirms the diagnosis when functionally significant mutations are found in both copies of the APRT gene, is not clinically indicated in patients with abolished APRT activity.</div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of… </p></div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of cystinuria. Annotations to Figure 4 Demonstration of aminoaciduria… </p></div>
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<div class="figure-caption-contents">Algorithm for diagnostic evaluation of cystinuria. Annotations to Figure 4 Demonstration of aminoaciduria with excessive levels of ornithine, arginine or lysine is not required for diagnosis. All patients with stones prior to age 30 years should be screened. Sodium-cyanide-nitroprusside test can yield false positive result in heterozygotes below the age of 2 years. A positive sodium-cyanide-nitroprusside test should be confirmed with 24 hour urine collection. Homozygotes have more than 170 μmol cystine/mmol creatinine (1500 μmol cystine/g creatinine). Heterozygotes (with <i>SLC7A9</i> mutations) will have between 11 and 110 μmol cystine/mmol creatinine (100-1000 μmol cystine/g creatinine), while other heterozygotes (with <i>SLC3A1</i> mutations) have normal cystine excretion (≤11 μmol cystine/mmol creatinine). Adult homozygotes excrete more than 1.3 mmol cystine per day (300 mg/day); heterozygotes (with <i>SLC7A9</i> mutations) will excrete more than 0.13 mmol/day (30 mg/day) while other heterozygotes (with <i>SLC3A1</i> mutations) have normal cystine excretion.</div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of Dent disease. Annotations to Figure 5 <sup> 1 </sup> The… </p></div>
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<div class="figure-caption-contents">Algorithm for diagnostic evaluation of Dent disease. Annotations to Figure 5 <sup>1</sup>The guideline does not address prenatal diagnosis. <sup>2</sup>Trace or greater by dipstick; or &gt;0.2 mg protein/mg creatinine; or &gt;100 mg protein/day. <sup>3</sup>Low molecular weight (LMW) proteinuria may be reduced in advanced renal insufficiency, or be present in renal failure from other causes, but remains helpful when markedly increased. <sup>4</sup>In the presence of kidney failure, defined as a measured or estimated glomerular filtration rate (GFR) less than 15 ml/min/1.73 m<sup>2</sup>, calcium stones, nephrocalcinosis, hypercalciuria, hypophosphatemia with or without rickets, and family history of stones, CKD, rickets or proteinuria may be sufficient to consider Dent disease, even in the absence of documented LMW proteinuria, and genetic testing could be considered. <sup>5</sup>Dent disease mutations have also been described in patients with histologic features of focal segmental glomerulosclerosis. <sup>6</sup>Hypercalciuria is defined as a 24 hour urine calcium or random urine calcium-to-creatinine ratio of &gt;95th percentile for age.
<table-wrap position="anchor" orientation="portrait"><table><tbody><tr><td align="left" colspan="3" rowspan="1"><b>Random urine calcium-to-creatinine ratio (Ca/Cr) by age</b> [119]</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"><b>Age (yr)</b></td><td colspan="2" valign="top" align="center" rowspan="1"><b>Ca/Cr ratio Upper limit of normal</b></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"/><td valign="top" align="center" rowspan="1" colspan="1">(mmol/mmol)</td><td valign="top" align="center" rowspan="1" colspan="1">(mg/mg)</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">0-1</td><td align="center" valign="top" rowspan="1" colspan="1">2.29</td><td align="center" valign="top" rowspan="1" colspan="1">0.81</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">1-2</td><td align="center" valign="top" rowspan="1" colspan="1">1.58</td><td align="center" valign="top" rowspan="1" colspan="1">0.56</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">2-3</td><td align="center" valign="top" rowspan="1" colspan="1">1.41</td><td align="center" valign="top" rowspan="1" colspan="1">0.50</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">3-5</td><td align="center" valign="top" rowspan="1" colspan="1">1.16</td><td align="center" valign="top" rowspan="1" colspan="1">0.41</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">5-7</td><td align="center" valign="top" rowspan="1" colspan="1">0.85</td><td align="center" valign="top" rowspan="1" colspan="1">0.30</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">7-10</td><td align="center" valign="top" rowspan="1" colspan="1">0.71</td><td align="center" valign="top" rowspan="1" colspan="1">0.25</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">10-14</td><td align="center" valign="top" rowspan="1" colspan="1">0.68</td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">14-17</td><td align="center" valign="top" rowspan="1" colspan="1">0.68</td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td></tr></tbody></table></table-wrap> <sup>7</sup>Possibly homozygous for mutation or with inactivation of normal X-chromosome. <sup>8</sup>Clinical criteria include low molecular weight (LMW) proteinuria plus one of the findings in Box A.</div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Annotations… </p></div>
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<div class="figure-caption-contents">Algorithm for diagnostic evaluation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Annotations to Figure 6 <sup>1</sup>The diagnosis of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is based on the triad of hypomagnesemia, hypercalciuria and nephrocalcinosis [5]. Tables of normal values should be consulted in the interpretation of any random urine solute-to-creatinine ratios. <sup>2</sup>All patients have nephrocalcinosis early in the course of the disease and 30% of patients eventually develop kidney stones. <sup>3</sup>Progressive chronic kidney disease (CKD) is apparent during childhood and adolescence, with half of patients reaching end stage renal disease (ESRD) at 20 years of age [5]. Renal histological findings are not specific and include calcium deposits, glomerular sclerosis, tubular atrophy and interstitial fibrosis consistent with a tubulointerstitial nephropathy. <sup>4</sup>The serum magnesium concentration at presentation has been shown to range from 0.23 to 0.61 mmol/L with a median concentration of 0.40 mmol/L [76]. <sup>5</sup>Normal limits for urinary calcium excretion is presented above in the annotations to Figure 5. <sup>6</sup>Hypermagnesuria is defined as the random urine magnesium-to-creatinine ratio of &gt;95th percentile for age.
<table-wrap position="anchor" orientation="portrait"><table><tbody><tr><td align="left" colspan="3" rowspan="1"><b>Random urine magnesium-to-creatinine (Mg/Cr) ratio by age</b> [119]</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"><b>Age (yr)</b></td><td colspan="2" valign="top" align="center" rowspan="1"><b>Mg/Cr ratioUpper limit of normal</b></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"/><td valign="top" align="center" rowspan="1" colspan="1">mmo/mmol</td><td valign="top" align="center" rowspan="1" colspan="1">mg/mg</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">0-1</td><td align="center" valign="top" rowspan="1" colspan="1">2.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.48</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">1-2</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.37</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">2-3</td><td align="center" valign="top" rowspan="1" colspan="1">1.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.34</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">3-5</td><td align="center" valign="top" rowspan="1" colspan="1">1.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.29</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">5-7</td><td align="center" valign="top" rowspan="1" colspan="1">1.0</td><td align="center" valign="top" rowspan="1" colspan="1">0.21</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">7-10</td><td align="center" valign="top" rowspan="1" colspan="1">0.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.18</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">10-14</td><td align="center" valign="top" rowspan="1" colspan="1">0.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.15</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">14-17</td><td align="center" valign="top" rowspan="1" colspan="1">0.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.13</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr></tbody></table></table-wrap> <sup>7</sup>Lower limits for the random citrate-to-creatinine ratio are presented below.
<table-wrap position="anchor" orientation="portrait"><table><tbody><tr><td align="left" colspan="3" rowspan="1"><b>Random urine citrate-to-creatinine (Cit/Cr) ratio by age</b> [120]</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"><b>Age (yr)</b></td><td colspan="2" valign="top" align="center" rowspan="1"><b>Cit/Cr ratio Lower limit of normal</b></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"/><td valign="top" align="center" rowspan="1" colspan="1">mmol/mmol</td><td valign="top" align="center" rowspan="1" colspan="1">mg/mg</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">0-5</td><td align="center" valign="top" rowspan="1" colspan="1">0.25</td><td align="center" valign="top" rowspan="1" colspan="1">0.42</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&gt;5</td><td align="center" valign="top" rowspan="1" colspan="1">0.15</td><td align="center" valign="top" rowspan="1" colspan="1">0.25</td></tr></tbody></table></table-wrap> <sup>8</sup>Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (HHNC) is caused by mutations in the <i>CLDN16</i> or <i>CLDN19</i> genes. Genetic testing may be available at research institutions. Ocular abnormalities are indicative of a CLDN19 defect.</div>
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<div class="figure-caption-contents"><p> Algorithm for diagnostic evaluation of primary hyperoxaluria. Annotations to Figure 7 <sup> 1 </sup> Chronic… </p></div>
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Figure 7
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<div class="figure-caption-contents">Algorithm for diagnostic evaluation of primary hyperoxaluria. Annotations to Figure 7 <sup>1</sup>Chronic kidney disease is defined as a glomerular filtration rate of less than 50 ml/min/1.73 m<sup>2</sup>, or serum creatinine that is greater than or equal to two times normal for age. <sup>2</sup>The guideline does not address prenatal diagnosis [121, 122]. <sup>3</sup>Urine oxalate-to-creatinine ratios in healthy children vary continuously by age. Tables of normal values should be consulted in interpretation of any random urine oxalate-to-creatinine ratio.
<table-wrap position="anchor" orientation="portrait"><table><tbody><tr><td align="left" colspan="3" rowspan="1"><b>Random urine oxalate-to-creatinine (Ox/Cr) ratio by age</b> [123-126]</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"><b>Age</b></td><td colspan="2" valign="top" align="center" rowspan="1"><b>Ox/Cr ratio Upper limit of normal</b></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"/><td valign="top" align="center" rowspan="1" colspan="1">(mmol/mmol)</td><td valign="top" align="center" rowspan="1" colspan="1">(mg/mg)</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&lt;6 months</td><td align="center" valign="top" rowspan="1" colspan="1">0.37</td><td align="center" valign="top" rowspan="1" colspan="1">0.29</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">6 months to 2 years</td><td align="center" valign="top" rowspan="1" colspan="1">0.26</td><td align="center" valign="top" rowspan="1" colspan="1">0.20</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&gt;2 years to 5 years</td><td align="center" valign="top" rowspan="1" colspan="1">0.14</td><td align="center" valign="top" rowspan="1" colspan="1">0.11</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">6 to 12 years</td><td align="center" valign="top" rowspan="1" colspan="1">0.08</td><td align="center" valign="top" rowspan="1" colspan="1">0.063</td></tr></tbody></table></table-wrap> Little data is available to guide interpretation of random urine oxalate-to-creatinine ratio in adolescents and adults. Upper limits of normal ratios declining to 0.04 by age 18-20 years and then remaining stable through adult age are suggested by available literature [125, 127]. In patients of all ages, confirmation of hyperoxaluria by a 24 hour urine collection with normalization of the oxalate excretion rate to 1.73 m<sup>2</sup> body surface area, is strongly recommended. From 2 years of age through adulthood, normal urine oxalate is constant at &lt;0.45 mmol/1.73 m<sup>2</sup>/24 hours [125]. <sup>4</sup>Urine and plasma oxalate and urine glycolate measurements for diagnostic testing should be obtained while the patient is not receiving pyridoxine or vitamin supplements. <sup>5</sup> Increased urine glycolate in the presence of hyperoxaluria is suggestive, but not diagnostic of primary hyperoxaluria (PH) type 1. Increased urine L-glycerate in a hyperoxaluric patient suggests PH type 2. <sup>6</sup>Urine oxalate-to-creatinine ratios are higher in very premature infants than in term infants, especially when they are receiving parenteral nutrition containing amino acids. The ratio falls when premature infants are receiving only glucose and electrolyte solutions [128]. <sup>7</sup>When very high oxalate or low dietary calcium is suspected as the cause of the hyperoxaluria, the diet should be corrected and the urine oxalate remeasured for verification. <sup>8</sup>In some cases with firm clinical diagnosis, only one mutation is found even after analysis for large rearrangements, suggesting that regulatory or deep intronic mutations may be the second, undetected mutation. In such cases, the finding of a single disease-associated mutation in the context of a typical phenotype supports the clinical diagnosis of PH.</div>
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<span class="docsum-authors full-authors">Haley WE, Ibrahim el-SH, Qu M, Cernigliaro JG, Goldfarb DS, McCollough CH.</span>
<span class="docsum-authors short-authors">Haley WE, et al.</span>
<span class="docsum-journal-citation full-journal-citation">Case Rep Radiol. 2015;2015:801021. doi: 10.1155/2015/801021. Epub 2015 Nov 25.</span>
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