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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Duarte Variant Galactosemia" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2020/06/25" /><meta name="citation_author" content="Judith L Fridovich-Keil" /><meta name="citation_author" content="Michael J Gambello" /><meta name="citation_author" content="Rani H Singh" /><meta name="citation_author" content="J Daniel Sharer" /><meta name="citation_pmid" content="25473725" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK258640/" /><meta name="citation_keywords" content="Duarte Galactosemia" /><meta name="citation_keywords" content="Duarte Galactosemia" /><meta name="citation_keywords" content="Galactose-1-phosphate uridylyltransferase" /><meta name="citation_keywords" content="GALT" /><meta name="citation_keywords" content="Duarte Variant Galactosemia" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Duarte Variant Galactosemia" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Judith L Fridovich-Keil" /><meta name="DC.Contributor" content="Michael J Gambello" /><meta name="DC.Contributor" content="Rani H Singh" /><meta name="DC.Contributor" content="J Daniel Sharer" /><meta name="DC.Date" content="2020/06/25" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK258640/" /><meta name="description" content="Infants with Duarte variant galactosemia who receive breast milk or a high galactose-containing formula (dairy milk-based formula) are typically asymptomatic and show the same prevalence of acute issues seen in the general newborn population. For decades it has been unclear whether Duarte variant galactosemia results in long-term developmental problems either with or without dietary intervention. However, a recent study of 350 children ages six to 12 years reported no detectable differences in developmental outcomes tested between children with Duarte variant galactosemia and controls, or among children with Duarte variant galactosemia as a function of galactose exposure in infancy. Premature ovarian insufficiency, which is common in classic galactosemia, also has not been reported for girls or women with Duarte variant galactosemia." /><meta name="og:title" content="Duarte Variant Galactosemia" /><meta name="og:type" content="book" /><meta name="og:description" content="Infants with Duarte variant galactosemia who receive breast milk or a high galactose-containing formula (dairy milk-based formula) are typically asymptomatic and show the same prevalence of acute issues seen in the general newborn population. For decades it has been unclear whether Duarte variant galactosemia results in long-term developmental problems either with or without dietary intervention. However, a recent study of 350 children ages six to 12 years reported no detectable differences in developmental outcomes tested between children with Duarte variant galactosemia and controls, or among children with Duarte variant galactosemia as a function of galactose exposure in infancy. Premature ovarian insufficiency, which is common in classic galactosemia, also has not been reported for girls or women with Duarte variant galactosemia." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK258640/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/duarte-gal/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK258640/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK258640_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK258640_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/duane/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/miyoshi/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK258640_"><span class="title" itemprop="name">Duarte Variant Galactosemia</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Duarte Galactosemia</div><p class="contrib-group"><span itemprop="author">Judith L Fridovich-Keil</span>, PhD, <span itemprop="author">Michael J Gambello</span>, MD, PhD, <span itemprop="author">Rani H Singh</span>, PhD, RD, and <span itemprop="author">J Daniel Sharer</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK258640_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK258640_ai__"><div class="contrib half_rhythm"><span itemprop="author">Judith L Fridovich-Keil</span>, PhD<div class="affiliation small">Department of Human Genetics
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Emory University School of Medicine
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Atlanta, Georgia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.yrome@vodirfj" class="oemail">ude.yrome@vodirfj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Michael J Gambello</span>, MD, PhD<div class="affiliation small">Division of Medical Genetics
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Department of Human Genetics
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Emory University School of Medicine
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Atlanta, Georgia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.yrome@lebmagm" class="oemail">ude.yrome@lebmagm</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Rani H Singh</span>, PhD, RD<div class="affiliation small">Division of Medical Genetics
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Department of Human Genetics
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Emory University School of Medicine
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Atlanta, Georgia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.yrome@hgnisr" class="oemail">ude.yrome@hgnisr</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">J Daniel Sharer</span>, PhD<div class="affiliation small">UAB Biochemical Genetics and Metabolic Disease Laboratory
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Department of Genetics
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University of Alabama at Birmingham
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Birmingham, Alabama<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.bau@rerahsd" class="oemail">ude.bau@rerahsd</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">December 4, 2014</span>; Last Revision: <span itemprop="dateModified">June 25, 2020</span>.</p><p><em>Estimated reading time: 20 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="duarte-gal.Summary" itemprop="description"><h2 id="_duarte-gal_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Infants with Duarte variant galactosemia who receive breast milk or a high galactose-containing formula (dairy milk-based formula) are typically asymptomatic and show the same prevalence of acute issues seen in the general newborn population. For decades it has been unclear whether Duarte variant galactosemia results in long-term developmental problems either with or without dietary intervention. However, a recent study of 350 children ages six to 12 years reported no detectable differences in developmental outcomes tested between children with Duarte variant galactosemia and controls, or among children with Duarte variant galactosemia as a function of galactose exposure in infancy. Premature ovarian insufficiency, which is common in classic galactosemia, also has not been reported for girls or women with Duarte variant galactosemia.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>Duarte variant galactosemia is diagnosed by a combination of biochemical and genetic testing. Specifically, erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity is typically about 25% of control activity, and <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/genotyping/">genotyping</a> reveals the presence of one <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic <i>GALT</i> variant together with either a heterozygous or <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> Duarte (D<sub>2</sub>) <i>GALT</i> variant.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Currently, there is no uniform standard of care regarding restriction of dietary galactose for infants with Duarte variant galactosemia. Thus, some health care providers, or parents, may choose to restrict dietary galactose in the first year of life, while others may not. When dietary galactose is restricted in infancy, centers often perform a galactose challenge around age one year followed by measurement of the erythrocyte galactose-1-phosphate level. If the level is within the normal range (<1.0 mg/dL), dietary restriction of galactose is generally discontinued. When dietary galactose is not restricted in infancy, some health care providers may still choose to check the erythrocyte galactose-1-phosphate level at age one year to confirm that the level is approaching the normal range.</p><p><i>Surveillance:</i> For infants on dietary restriction of galactose: if the erythrocyte galactose-1-phosphate level is >1.0 mg/dL following a galactose challenge at age one year, galactose restriction may be resumed. In this case, the galactose challenge and measurement of erythrocyte galactose-1-phosphate level may be repeated every four to six months until the erythrocyte galactose-1-phosphate level stabilizes at <1.0 mg/dL.</p><p><i>Agents/circumstances to avoid:</i> Opinion varies as to whether avoidance of all dairy products (including breast milk and dairy milk-based formula) until age one year is warranted.</p><p><i>Evaluation of relatives at risk:</i> If families with one child with Duarte variant galactosemia wish to evaluate their other children for Duarte variant galactosemia, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> for the <i>GALT</i> variants identified in the family can be performed.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Duarte variant galactosemia is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. When one parent is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the <i>GALT</i> D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> and the other parent is heterozygous for a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each child has a 25% chance of having Duarte variant galactosemia, a 25% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of the D<sub>2</sub> allele, a 25% chance of being an asymptomatic carrier of the <i>GALT</i> pathogenic variant, and a 25% chance of being unaffected and also not a carrier of either <i>GALT</i> variant. Carrier testing for at-risk relatives and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for pregnancies at increased risk requires prior identification of the <i>GALT</i> variants in the family and determination of the parental origin of each allele.</p></div></div><div id="duarte-gal.Diagnosis"><h2 id="_duarte-gal_Diagnosis_">Diagnosis</h2><p>Duarte variant galactosemia is defined by a combination of the following:</p><ul><li class="half_rhythm"><div>One <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (G <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>) present in the <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> state plus the <i>GALT</i> Duarte (D<sub>2</sub>) variant allele present in either the heterozygous state (<i>in trans</i> to the G allele) or in the <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> state (both <i>in</i>
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<a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> and <i>in</i>
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<a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> to the G allele)</div></li><li class="half_rhythm"><div>Erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity that is typically about 25% of control activity</div></li></ul><div id="duarte-gal.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Duarte variant galactosemia, caused by a partial deficiency in erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme, <b>should be suspected</b> in infants with a positive newborn screening (NBS) result for galactosemia but few if any clinical findings when on a high-galactose diet (e.g., breast milk or a dairy milk-based formula).</p><p>
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<b>Positive NBS result</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">NBS for classic galactosemia and its variants (including Duarte variant galactosemia) is primarily based on quantification of erythrocyte GALT enzyme activity on dried blood spots.</div><div class="half_rhythm">Note: While all states in the US now include screening for classic galactosemia in their NBS panel, some states have set their newborn screening GALT enzyme activity cutoff level to ensure the detection of classic and clinical variant galactosemia while minimizing false positives and the detection of infants with Duarte variant galactosemia [<a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>]. In those states, a NBS result for galactosemia that is not flagged as "abnormal" may not be informative for Duarte variant galactosemia.</div></li><li class="half_rhythm"><div class="half_rhythm">GALT enzyme activity below the cutoff defined by the screening program is considered positive and requires follow-up diagnostic testing (see <a href="#duarte-gal.Establishing_the_Diagnosis">Establishing the Diagnosis</a>).</div><div class="half_rhythm">Note: GALT is a labile enzyme; exposure of the sample to heat and/or humidity in storage or transit (as sometimes occurs in hot climates especially during the summer months) can result in artifactual loss of activity and higher false positive rates.</div></li></ul><p><b>Follow-up testing.</b> Quantitative testing of erythrocyte GALT enzyme activity is the first recommended follow-up approach for a positive NBS result for galactosemia. Testing of erythrocyte galactose-1-phosphate and/or urinary galactitol may also be useful as a baseline or if the infant is on a high-galactose diet (e.g., breast milk or a dairy milk-based formula).</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Erythrocyte GALT</b>
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<b>enzyme activity</b> that is typically about 25% of control activity is consistent with a diagnosis of Duarte variant galactosemia (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>, <a class="bk_pop" href="#duarte-gal.REF.walter.2014">Walter & Fridovich-Keil [2014]</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al [2015]</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>The erythrocyte galactose-1-phosphate (Gal-1P) concentration</b> may range from high (>30 mg/dL) to normal (<1.0 mg/dL) depending on the infant's recent dietary exposure to breast milk or galactose-containing formula.</div><div class="half_rhythm">Note: Dairy milk products contain lactose, which is metabolized to glucose and galactose by normal digestion. Therefore, any product that contains dairy milk and/or lactose also contains galactose.</div><ul><li class="half_rhythm"><div>Erythrocyte galactose-1-phosphate concentrations may exceed 30 mg/dL within the first few weeks of life; however, even in infants with Duarte variant galactosemia who are not treated with a galactose-restricted diet the concentration tends to normalize (<1.0 mg/dL) within the first year [<a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2008.206">Ficicioglu et al 2008</a>, <a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2010.1177">Ficicioglu et al 2010</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>].</div></li><li class="half_rhythm"><div>Erythrocyte galactose-1-phosphate concentration in infants placed on a galactose-restricted diet normalizes rapidly, decreasing to an almost undetectable level within one month [<a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2008.206">Ficicioglu et al 2008</a>].</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm"><b>Urinary galactitol</b> may be elevated, but not to the same extent seen in classic galactosemia [<a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2010.1177">Ficicioglu et al 2010</a>].</div><ul><li class="half_rhythm"><div>The mean urinary galactitol level in a cohort of young children with Duarte variant galactosemia on unrestricted (regular) diet at age one year was 46±14 mmol/mol creatinine [<a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2008.206">Ficicioglu et al 2008</a>], and in a cohort of children with Duarte variant galactosemia on unrestricted galactose (regular) diet at ages one to six years was 31.6 mmol/mol creatinine.</div></li><li class="half_rhythm"><div>Mean urinary galactitol in controls (<1 year of age) was reported to range from 2-78 mmol/mol creatinine, and mean urinary galactitol in infants (<1 year) with classic galactosemia was 466±166 mmol/mol [<a class="bk_pop" href="#duarte-gal.REF.palmieri.1999.1294">Palmieri et al 1999</a>].</div></li></ul></li></ul><p>Click <a href="/books/NBK258640/bin/duarte-gal-historical_tests.pdf">here</a> (pdf) for information on testing of historical interest.</p></div><div id="duarte-gal.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of Duarte variant galactosemia <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> by a combination of: (1) erythrocyte GALT enzyme activity that is typically about 25% of control activity; and (2) molecular genetic test results that identify the presence of one <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic <i>GALT</i> variant together with either a heterozygous or <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> Duarte (D<sub>2</sub>) <i>GALT</i> variant (<a href="/books/NBK258640/table/duarte-gal.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobduartegalTmoleculargenetictestingu">Table 1</a>).</p><p><b>Duarte variant (D<sub>2</sub>) <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</b> Five sequence changes in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration are found on the Duarte variant (D<sub>2</sub>) allele.</p><p>Of primary importance is a 4-bp <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/promoter-region/">promoter region</a> (<a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object" rid-ob="figobduartegalTgaltvariantsassociatedwi">c.-119_-116delGTCA</a>) that is considered to cause diminished transcription (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>). The four remaining variants unique to the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> are described in <a href="#duarte-gal.Molecular_Genetics">Molecular Genetics</a>, <b>Benign variants</b> and <a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object" rid-ob="figobduartegalTgaltvariantsassociatedwi">Table 3</a>.</p><p><b>Pathogenic <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</b> A <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is one that results in absent or barely detectable GALT enzyme activity when it occurs in the <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> state or the <a class="def" href="/books/n/gene/glossary/def-item/compound-heterozygous/">compound heterozygous</a> state with another pathogenic variant; the resulting phenotypes are classic (<1% GALT activity) or clinical variant galactosemia (1%-10% GALT activity) (see <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>). Note: Pathogenic <i>GALT</i> variants are sometimes referred to collectively as G alleles.</p><p><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>GALT</i> detects small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-gene deletions/duplications are not detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</p><ul><li class="half_rhythm"><div><b>Sequence analysis</b> can detect the D<sub>2</sub>
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<i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> as well as most <i>GALT</i> pathogenic variants. However, a nearly whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of <i>GALT</i> that has been reported predominantly among affected individuals of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> ancestry (see <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>) may not be detected by traditional sequencing technologies.</div></li><li class="half_rhythm"><div>If the D<sub>2</sub> variant is identified in a sample in which GALT enzyme activity is about 25%, but no <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <b><a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a></b> should be considered. This is especially true if variants characteristic of the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> appear <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a>; the other allele of <i>GALT</i> may be deleted.</div></li></ul><p><b>Interpretation of molecular genetic test results.</b> See <a href="#duarte-gal.Molecular_Genetics">Molecular Genetics</a> for details.</p><div id="duarte-gal.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Duarte Variant Galactosemia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK258640/table/duarte-gal.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duarte-gal.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_2" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands in Whom the Method Detects:</th></tr><tr><th headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3" id="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">The Duarte (D<sub>2</sub>) variant</th><th headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3" id="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">A <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GALT</i>
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</td><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3 hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3 hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>95%</td></tr><tr><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/<a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> analysis <sup>4</sup></td><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3 hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0 <sup>5</sup></td><td headers="hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_1_3 hd_h_duarte-gal.T.molecular_genetic_testing_u_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Estimated <1% <sup>6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="duarte-gal.TF.1.1"><p class="no_margin">See <a href="/books/NBK258640/#duarte-gal.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="duarte-gal.TF.1.2"><p class="no_margin">See <a href="#duarte-gal.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="duarte-gal.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="duarte-gal.TF.1.4"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>5. </dt><dd><div id="duarte-gal.TF.1.5"><p class="no_margin">Deletion/<a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> analysis will not identify the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</p></div></dd><dt>6. </dt><dd><div id="duarte-gal.TF.1.6"><p class="no_margin">Exon and multiexon <i>GALT</i> deletions have been reported; while rare overall, such deletions may be common in specific populations. See <a href="/books/NBK258640/#duarte-gal.molgen.TA">Table A</a>, <b>Locus-Specific Databases</b>.</p></div></dd></dl></div></div></div></div></div><div id="duarte-gal.Clinical_Characteristics"><h2 id="_duarte-gal_Clinical_Characteristics_">Clinical Characteristics</h2><div id="duarte-gal.Clinical_Description"><h3>Clinical Description</h3><p><b>The neonatal period.</b> Infants with Duarte variant galactosemia who are on breast milk or a high galactose-containing formula (here referred to as "dairy milk-based formula") are typically asymptomatic. However, anecdotal reports suggest that some infants with Duarte variant galactosemia, like some infants who do not have any form of galactosemia, may experience jaundice or other acute symptoms that resolve over time following removal of breast milk or dairy milk-based formula from the diet [Author, personal observation].</p><p>Note: Resolution of acute symptoms over time following removal of breast milk or dairy milk-based formula from the diet does <b>not</b> confirm that the problem was related to galactose.</p><p><b>Neurodevelopment.</b> A recent study by <a class="bk_pop" href="#duarte-gal.REF.carlock.2019.e20182516">Carlock et al [2019]</a> reported 73 outcomes representing five general domains of development (cognitive, physical, motor, socio-emotional, and speech/language) in 350 children, 206 with Duarte variant galactosemia and 144 controls. Cases and controls were derived from the same set of families and ascertained from 13 different states in the United States, so they were well-matched by geography, race, socioeconomic status, and other covariates.</p><ul><li class="half_rhythm"><div>No significant difference in prevalence of complications was seen between affected individuals and controls for any of the outcomes tested.</div></li><li class="half_rhythm"><div>No significant difference was seen comparing developmental outcomes of children with Duarte variant galactosemia who consumed breast milk or dairy milk-based formula versus low-galactose formula in the first year of life.</div></li><li class="half_rhythm"><div>Combined, these results strongly support the assertion that Duarte variant galactosemia does not cause developmental complications in children with or without dietary restriction of galactose.</div></li></ul><p>Note: The developmental outcomes of school-age children with Duarte variant galactosemia has been a point of controversy for some time, in part because a study by <a class="bk_pop" href="#duarte-gal.REF.powell.2009.874">Powell et al [2009]</a> reported that children age three to ten years with Duarte variant galactosemia in metropolitan Atlanta were more likely than age-matched controls from the general population to receive speech-language intervention in public school. However, a reconsideration of these data in 2019 revealed a number of important confounding factors that may explain the results observed [<a class="bk_pop" href="#duarte-gal.REF.fridovichkeil.2019.2683">Fridovich-Keil et al 2019</a>].</p><p><b>Ovarian function in females.</b> A study of anti-müllerian hormone in young girls with enzymatically and/or molecularly confirmed Duarte variant galactosemia demonstrated no evidence of premature ovarian insufficiency [<a class="bk_pop" href="#duarte-gal.REF.badik.2011.469">Badik et al 2011</a>]. Further, family studies of newly diagnosed infants with classic or Duarte variant galactosemia sometimes reveal that the mother herself has Duarte variant galactosemia, confirming that women with Duarte variant galactosemia can be fertile and carry a pregnancy successfully to term [Author, personal observation].</p></div><div id="duarte-gal.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>No significant <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a>-<a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> relationships for Duarte variant galactosemia with regard to different pathogenic <i>GALT</i> alleles <i>in</i>
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<a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> with the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> have been reported.</p></div><div id="duarte-gal.Nomenclature"><h3>Nomenclature</h3><p>Duarte variant galactosemia may also be called Duarte galactosemia, DG, or biochemical variant galactosemia.</p><p>Sometimes, Duarte variant galactosemia is simply called variant galactosemia; however, this term is better reserved for individuals now said to have "<a href="/books/n/gene/galactosemia/">clinical variant galactosemia</a>," who do not have a <i>GALT</i> D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> but rather have <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>GALT</i> pathogenic variants of which at least one is <a class="def" href="/books/n/gene/glossary/def-item/hypomorphic/">hypomorphic</a>, resulting in a low level of residual GALT enzyme activity. Of note, galactokinase deficiency and epimerase deficiency are also sometimes called "variant" galactosemia. Thus, unless the term Duarte, D, DG, or D<sub>2</sub> is explicit, the reader should not assume that the term variant galactosemia implies Duarte variant galactosemia.</p></div><div id="duarte-gal.Prevalence"><h3>Prevalence</h3><p>The prevalence of Duarte variant galactosemia is difficult to confirm due to incomplete ascertainment. Duarte variant galactosemia is detected in as many as 1:3,500 screened births in some states and essentially zero in others, largely reflecting differences in NBS protocols [<a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>] (see <a href="#duarte-gal.Diagnosis">Diagnosis</a>, <b>Erythrocyte GALT enzyme activity</b>).</p><p>The true prevalence of Duarte variant galactosemia in the US newborn population is estimated to be approximately tenfold the prevalence of classic galactosemia [<a class="bk_pop" href="#duarte-gal.REF.fernhoff.2010.1045">Fernhoff 2010</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>].</p><p>Among newborns diagnosed with Duarte variant galactosemia some patterns implicating differential prevalence by race are evident [<a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>]. For example, Duarte variant galactosemia is more common among infants of European ancestry and less prevalent among infants of African, African American, or Asian ancestry. These differences parallel recognized differences among these populations in the prevalence of the D<sub>2</sub> variant and/or other known <i>GALT</i> pathogenic variants [<a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>].</p></div></div><div id="duarte-gal.Genetically_Related_Allelic_D"><h2 id="_duarte-gal_Genetically_Related_Allelic_D_">Genetically Related (Allelic) Disorders</h2><p><a href="/books/n/gene/galactosemia/">Classic galactosemia and clinical variant galactosemia</a> are also associated with mutation of <i>GALT.</i> The genotypes that give rise to these phenotypes have two <i>GALT</i> pathogenic variants that result in either absent or only trace GALT enzyme activity.</p><p>The Los Angeles (LA) variant (D<sub>1</sub>) has the identical p.Asn314Asp <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant as the Duarte (D<sub>2</sub>) variant but does not have the promoter <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> c.-119_-116delGTCA. Instead, it is in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration with the missense variant p.Leu218=. This variant does not cause galactosemia and is associated with normal to increased erythrocyte GALT enzyme activity (see <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>).</p></div><div id="duarte-gal.Differential_Diagnosis"><h2 id="_duarte-gal_Differential_Diagnosis_">Differential Diagnosis</h2><p>Most infants with Duarte variant galactosemia are diagnosed because of a positive NBS result for galactosemia. The differential diagnosis of a positive NBS for galactosemia is:</p><ul><li class="half_rhythm"><div>
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<a href="/books/n/gene/galactosemia/">Classic galactosemia and clinical variant galactosemia</a>
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</div></li><li class="half_rhythm"><div>Duarte variant galactosemia</div></li><li class="half_rhythm"><div>
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<a href="/books/n/gene/gale-def/">GALE (epimerase) deficiency galactosemia </a>
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</div></li><li class="half_rhythm"><div>GALK (galactokinase) deficiency (OMIM <a href="https://omim.org/entry/230200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">230200</a>)</div></li><li class="half_rhythm"><div>GALM deficiency galactosemia (OMIM <a href="https://omim.org/entry/618881" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618881</a>)</div></li><li class="half_rhythm"><div>Compromised galactose utilization not caused by a Leloir enzyme deficiency (e.g., Fanconi-Bickel syndrome [OMIM <a href="https://www.omim.org/entry/227810" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">227810</a>] or portosystemic shunt [<a class="bk_pop" href="#duarte-gal.REF.bernard.2012.273">Bernard et al 2012</a>]).</div></li><li class="half_rhythm"><div>A false positive result that includes:</div><ul><li class="half_rhythm"><div>Heterozygotes (carriers) for a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>;</div></li><li class="half_rhythm"><div>Other combinations of partially impaired <i>GALT</i> alleles (e.g., D<sub>2</sub> variant homozygotes);</div></li><li class="half_rhythm"><div>Individuals with completely normal <i>GALT</i> alleles and enzyme activity whose samples were technically compromised by exposure to heat and/or humidity in storage or transit.</div></li></ul></li></ul><p><b>Erythrocyte GALT enzyme activity.</b> Measuring erythrocyte GALT enzyme activity is often the first step in differential diagnosis of a positive NBS result for galactosemia.</p><div id="duarte-gal.T.disorders_to_consider_given" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Disorders to Consider Given a Newborn Screening Result Suggestive of Galactosemia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK258640/table/duarte-gal.T.disorders_to_consider_given/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duarte-gal.T.disorders_to_consider_given_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Erythrocyte GALT Enzyme Activity <sup>1</sup></th><th id="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diagnosis</th></tr></thead><tbody><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Very low to undetectable</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/galactosemia/">Classic galactosemia</a>
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</td></tr><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-10%</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/galactosemia/">Clinical variant galactosemia</a>
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</td></tr><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~15%-33%</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Duarte variant galactosemia <sup>2</sup></td></tr><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~50%</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Carrier of 1 pathogenic <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> or <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> for the D<sub>2</sub> variant</td></tr><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~75%</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Carrier of 1 D<sub>2</sub> variant</td></tr><tr><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Indistinguishable</td><td headers="hd_h_duarte-gal.T.disorders_to_consider_given_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/gale-def/">GALE (epimerase) deficiency</a> or GALK (galactokinase) deficiency <sup>3</sup> or GALM (galactose mutarotase) deficiency <sup>4</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="duarte-gal.TF.2.1"><p class="no_margin">Compared with the erythrocyte GALT enzyme activity of controls</p></div></dd><dt>2. </dt><dd><div id="duarte-gal.TF.2.2"><p class="no_margin">See <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>.</p></div></dd><dt>3. </dt><dd><div id="duarte-gal.TF.2.3"><p class="no_margin"><a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al [2015]</a></p></div></dd><dt>4. </dt><dd><div id="duarte-gal.TF.2.4"><p class="no_margin"><a class="bk_pop" href="#duarte-gal.REF.iwasawa.2019.362">Iwasawa et al [2019]</a>, <a class="bk_pop" href="#duarte-gal.REF.wada.2019.1286">Wada et al [2019]</a></p></div></dd></dl></div></div></div><p><b>Erythrocyte galactose-1-phosphate</b> levels in infants with Duarte variant galactosemia exposed to galactose may be elevated. Although these erythrocyte galactose-1-phosphate levels overlap those seen in classic galactosemia, they typically do not exceed 30 mg/dL [<a class="bk_pop" href="#duarte-gal.REF.ficicioglu.2008.206">Ficicioglu et al 2008</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>]. In contrast, in classic galactosemia levels >50 mg/dL are not uncommon, and in some samples erythrocyte galactose-1-phosphate exceeds 100 mg/dL [<a class="bk_pop" href="#duarte-gal.REF.walter.2014">Walter & Fridovich-Keil 2014</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>].</p></div><div id="duarte-gal.Management"><h2 id="_duarte-gal_Management_">Management</h2><div id="duarte-gal.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>An infant who is symptomatic should be seen by a metabolic specialist for evaluation for other possible conditions.</p><p>To assist the family with understanding the genetic implications of a diagnosis of Duarte variant galactosemia for the child and family, a <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> consultation is recommended.</p></div><div id="duarte-gal.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Current data suggest that infants and children with Duarte variant galactosemia are not at increased risk for acute or long-term developmental [<a class="bk_pop" href="#duarte-gal.REF.carlock.2019.e20182516">Carlock et al 2019</a>] or ovarian [<a class="bk_pop" href="#duarte-gal.REF.badik.2011.469">Badik et al 2011</a>] complications regardless of dietary exposure to galactose in infancy. In light of these data, some healthcare providers may conclude that dietary intervention in Duarte variant galactosemia is neither required nor desirable [<a class="bk_pop" href="#duarte-gal.REF.mccandless.2019.e20183292">McCandless 2019</a>]; however, other providers may disagree.</p><p><b>If the decision is made to restrict dietary galactose,</b> health care providers may recommend one or more of the following [<a class="bk_pop" href="#duarte-gal.REF.fernhoff.2010.1045">Fernhoff 2010</a>, <a class="bk_pop" href="#duarte-gal.REF.pyhtila.2015.79">Pyhtila et al 2015</a>]:</p><ul><li class="half_rhythm"><div>Immediate dietary galactose restriction for infants with erythrocyte galactose-1-phosphate >10 mg/dL</div></li><li class="half_rhythm"><div>Full dietary restriction of galactose by feeding low-galactose formula, through age one year, at which time a galactose challenge is performed</div></li><li class="half_rhythm"><div>A compromise approach in which parents wishing to breastfeed alternate breast milk with a low-galactose formula</div></li></ul><p><b>The galactose challenge</b>. If dietary galactose is restricted, conducting a galactose challenge by age 12 months should be considered. For example:</p><ul><li class="half_rhythm"><div>Obtain a baseline erythrocyte galactose-1-phosphate level at diagnosis and again around age six months (i.e., after the introduction of solid foods).</div></li><li class="half_rhythm"><div>At age 12 months, gradually liberalize the dietary intake of galactose, and obtain an erythrocyte galactose-1-phosphate level one month later.</div></li><li class="half_rhythm"><div>If the erythrocyte galactose-1-phosphate level is within the normal range (<1.0 mg/dL) despite dairy milk ingestion, dietary restriction of galactose is not resumed.</div></li></ul></div><div id="duarte-gal.Surveillance"><h3>Surveillance</h3><p>Most individuals diagnosed with Duarte variant galactosemia as infants who are followed by a genetics or metabolic specialist are discharged from follow up after a successful galactose challenge at age one year (see <a href="#duarte-gal.Treatment_of_Manifestations">Treatment of Manifestations</a>).</p><p>Among children with Duarte variant galactosemia who have been restricted for dietary galactose as infants, if the erythrocyte galactose-1-phosphate level is >1.0 mg/dL following a galactose challenge at age one year, galactose restriction may be resumed, and the galactose challenge and measurement of erythrocyte galactose-1-phosphate level repeated every four to six months until the level stabilizes at <1.0 mg/dL.</p></div><div id="duarte-gal.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Some health care providers recommend avoiding all high galactose foods (e.g., dairy milk products) until age one year; other health care providers argue that this precaution is neither warranted nor desirable [<a class="bk_pop" href="#duarte-gal.REF.mccandless.2019.e20183292">McCandless 2019</a>].</p></div><div id="duarte-gal.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#duarte-gal.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="duarte-gal.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies for a wide range of diseases and conditions. Note: As there are no negative health consequences documented for this condition, there may not be any clinical trials.</p></div></div><div id="duarte-gal.Genetic_Counseling"><h2 id="_duarte-gal_Genetic_Counseling_">Genetic Counseling</h2><p>
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||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
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||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="duarte-gal.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Duarte variant galactosemia is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p><p>Individuals with Duarte variant galactosemia have at least one Duarte (D<sub>2</sub>) variant <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> and one <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (G allele) in <a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> configuration (on homologous chromosomes).</p></div><div id="duarte-gal.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Molecular genetic testing is needed to clarify the genetic status of parents.</div></li><li class="half_rhythm"><div>Typically, one parent of a child with Duarte variant galactosemia carries the Duarte (D<sub>2</sub>) variant <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> and the other parent carries a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (G allele).</div></li><li class="half_rhythm"><div>Rarely, a parent may have Duarte variant galactosemia or another <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> that includes the D<sub>2</sub> variant (e.g., homozygosity for the Duarte variant). Recurrence risks may vary for these couples.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) of a single <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> configuration with a normal <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>, or people who carry either one or two D<sub>2</sub> alleles, are clinically asymptomatic and do not have Duarte variant galactosemia.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If one parent is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> and the other parent is heterozygous for a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> each sib has at conception:</div><ul><li class="half_rhythm"><div>A 25% chance of having Duarte variant galactosemia;</div></li><li class="half_rhythm"><div>A 25% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>;</div></li><li class="half_rhythm"><div>A 25% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (G <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>);</div></li><li class="half_rhythm"><div>A 25% chance of being unaffected and not a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of either variant.</div></li></ul></li><li class="half_rhythm"><div>In some families, it is possible for the sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with Duarte variant galactosemia to have <a href="/books/n/gene/galactosemia/">classic or clinical variant galactosemia</a> depending on the genetic status of the proband's parents. For example, if one parent has Duarte variant galactosemia and the other parent is a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> for a pathogenic <i>GALT</i> variant, each sib at conception has:</div><ul><li class="half_rhythm"><div>A 25% chance of having Duarte variant galactosemia;</div></li><li class="half_rhythm"><div>A 25% chance of having classic galactosemia or clinical variant galactosemia;</div></li><li class="half_rhythm"><div>A 25% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>;</div></li><li class="half_rhythm"><div>A 25% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (G <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>).</div></li></ul></li><li class="half_rhythm"><div>Risks to sibs are different for other parental genotypes. Referral for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> is indicated for such families.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) of (1) a single <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> configuration with a normal <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> or (2) either one or two D<sub>2</sub>
|
||
<i>GALT</i> alleles are clinically asymptomatic and do not have Duarte variant galactosemia.</div></li></ul><p>
|
||
<b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The offspring of an individual with Duarte variant galactosemia are typically heterozygotes (carriers) of a <i>GALT</i> variant <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> (i.e., either a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> or the D<sub>2</sub> allele).</div></li><li class="half_rhythm"><div>Accurate determination of the risk to offspring is only possible after <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s reproductive partner.</div></li></ul><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>; typically, one side of the family will be at increased risk of carrying a D<sub>2</sub>
|
||
<i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> while the other side of the family will be at increased risk of carrying a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="duarte-gal.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>GALT</i> variants in the family and determination of the parental origin of each <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</p></div><div id="duarte-gal.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> status, and discussion of available <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> options is before pregnancy.</div></li><li class="half_rhythm"><div>Although current research indicates that individuals with Duarte variant galactosemia are typically asymptomatic [<a class="bk_pop" href="#duarte-gal.REF.badik.2011.469">Badik et al 2011</a>, <a class="bk_pop" href="#duarte-gal.REF.carlock.2019.e20182516">Carlock et al 2019</a>], they are heterozygotes (carriers) for a pathogenic <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>. It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who have Duarte variant galactosemia, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="duarte-gal.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>GALT</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="duarte-gal.Resources"><h2 id="_duarte-gal_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>Duarte Galactosemia</b>
|
||
</div><div>
|
||
<a href="http://duartegalactosemia.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.duartegalactosemia.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Medical Home Portal</b>
|
||
</div><div>
|
||
<a href="https://www.medicalhomeportal.org/diagnoses-and-conditions/galactosemia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Galactosemia</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Newborn Screening in Your State</b>
|
||
</div><div>Health Resources & Services Administration</div><div>
|
||
<a href="https://newbornscreening.hrsa.gov/your-state" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">newbornscreening.hrsa.gov/your-state</a>
|
||
</div></li></ul>
|
||
</div><div id="duarte-gal.Molecular_Genetics"><h2 id="_duarte-gal_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="duarte-gal.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Duarte Variant Galactosemia: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK258640/table/duarte-gal.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duarte-gal.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_duarte-gal.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_duarte-gal.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_duarte-gal.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_duarte-gal.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_duarte-gal.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_duarte-gal.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/2592" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>GALT</i>
|
||
</a>
|
||
</td><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2592" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">9p13<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P07902" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Galactose-1-phosphate uridylyltransferase</a>
|
||
</td><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/GALT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GALT database</a>
|
||
</td><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GALT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GALT</a>
|
||
</td><td headers="hd_b_duarte-gal.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GALT[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GALT</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="duarte-gal.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="duarte-gal.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Duarte Variant Galactosemia (<a href="/omim/230400,606999" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK258640/table/duarte-gal.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duarte-gal.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/230400" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">230400</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GALACTOSEMIA I; GALAC1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/606999" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">606999</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE; GALT</td></tr></tbody></table></div></div><div id="duarte-gal.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The mechanism of pathogenesis of the <i>GALT</i> D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> was a point of some confusion in the past (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>), likely reflecting the complex nature of the allele and the fact that the linked 4-bp promoter <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> (c.-119_-116delGTCA) was not initially recognized. The consensus is now that this 4-bp promoter deletion is actually the causal variant, leading to slight impairment of expression of what is a fully functional GALT protein.</p><p>The mechanism of pathogenesis of different <i>GALT</i> pathogenic variants as a cause of classic / clinical variant galactosemia is described in <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>.</p><p><b>Gene structure.</b> See <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a> for information about <i>GALT</i>. See also <a href="/books/NBK258640/#duarte-gal.molgen.TA">Table A</a>, <b>Gene</b>.</p><p>
|
||
<b>Benign variants</b>
|
||
</p><ul><li class="half_rhythm"><div><b>Duarte variant (D<sub>2</sub>) <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</b> Some consider the D<sub>2</sub> variant allele itself to be benign. Five sequence changes in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration are found on the D<sub>2</sub> allele.</div><ul><li class="half_rhythm"><div>Four are noncoding nucleotide variants that are unique to the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> (see <a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object" rid-ob="figobduartegalTgaltvariantsassociatedwi">Table 3</a>).</div></li><li class="half_rhythm"><div>Of primary importance is a 4-bp <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/promoter-region/">promoter region</a> (c.-119_-116delGTCA) that slightly impairs <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> expression (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>).</div></li><li class="half_rhythm"><div>The three remaining variants unique to D<sub>2</sub> are c.378-27G>C, c.508-24G>A, and c.507+62G>A.</div></li><li class="half_rhythm"><div>The fifth sequence change is the <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant c.940A>G (p.Asn314Asp, also called N314D); while always on the D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>, c.940A>G also occurs on other functionally normal <i>GALT</i> alleles (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>).</div></li></ul></li><li class="half_rhythm"><div><b>Los Angeles (or D<sub>1</sub>) variant <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a></b> results in no diminution of GALT enzyme activity and is considered benign. Note: The Los Angeles (LA) <i>GALT</i> variant (D<sub>1</sub>) has the identical c.940A>G <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant as the D<sub>2</sub> variant but does not have the c.-119_-116delGTCA promoter <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a>. Instead, it is in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration with the silent variant c.652C>T (p.Leu218=, also called L218L). See <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>. The D<sub>1</sub> variant allele does not cause galactosemia and is associated with normal or slightly increased erythrocyte GALT enzyme activity (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>).</div></li></ul><div id="duarte-gal.T.galt_variants_associated_wi" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p><i>GALT</i> Variants Associated with the D<sub>2</sub> Allele Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duarte-gal.T.galt_variants_associated_wi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.-119_-116delGTCA</td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA <sup>2</sup></td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_3" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nucleotide/22165415" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000155<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/22165416" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000146<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td></tr><tr><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.940A>G</td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn314Asp</td></tr><tr><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.378-27G>C<br />(IVS4-27G>C)</td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.508-24G>A<br />(IVS5-24G>A)</td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.507+62G>A<br />(IVS5-62G>A)</td><td headers="hd_h_duarte-gal.T.galt_variants_associated_wi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="duarte-gal.TF.3.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd><dt>2. </dt><dd><div id="duarte-gal.TF.3.2"><p class="no_margin">Reduces promoter function (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>)</p></div></dd></dl></div></div></div><p><b>Interpretation of molecular genetic test results.</b> Although rare, some individuals with Duarte variant galactosemia are <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> for <a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object" rid-ob="figobduartegalTgaltvariantsassociatedwi">c.940A>G</a> (p.Asn314Asp, also called N314D) and <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a pathogenic <i>GALT</i> variant, indicating that the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> coexists in these individuals in a <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration with either a D<sub>2</sub> or D<sub>1</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</p><p>Also, rarely, some individuals with classic galactosemia (who by definition have <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>GALT</i> pathogenic variants) may also have either a D<sub>2</sub> or D<sub>1</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration with one or both pathogenic <i>GALT</i> variants.</p><p>Therefore, demonstrating the presence of the D<sub>2</sub> variant – or any of the individual <i>GALT</i> sequence changes associated with a D<sub>2</sub> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> (e.g., <a href="/books/NBK258640/table/duarte-gal.T.galt_variants_associated_wi/?report=objectonly" target="object" rid-ob="figobduartegalTgaltvariantsassociatedwi">c.940A>G</a>; p.Asn314Asp, or N314D) – does not confirm a diagnosis of Duarte variant galactosemia or rule out a diagnosis of classic galactosemia. The presence of <i>GALT</i> variants must always be interpreted in conjunction with GALT enzyme activity levels.</p><p>Of note, the parents of a child with an identified D<sub>2</sub>
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<i>GALT</i> variant <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> and a <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> allele can undergo <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> themselves to determine whether each parent carries one variant, or whether both <i>GALT</i> variants are found in one parent while the other parent carries neither variant.</p><ul><li class="half_rhythm"><div>If each parent carries one variant found in the child, the D<sub>2</sub> and pathogenic <i>GALT</i> variants identified in the child are in <a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> configuration (on separate chromosomes) consistent with a diagnosis of Duarte variant galactosemia in the child.</div></li><li class="half_rhythm"><div>If one parent carries both the D<sub>2</sub> and pathogenic <i>GALT</i> variants identified in the child while the other parent carries neither, the D<sub>2</sub> and pathogenic <i>GALT</i> variants in the child are most likely in <a class="def" href="/books/n/gene/glossary/def-item/cis/"><i>cis</i></a> configuration (coexisting on the same <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a>) consistent with a diagnosis of unaffected galactosemia <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> rather than Duarte variant galactosemia in the child. In this scenario, the child would also be expected to show a GALT enzyme activity level close to 50% of control.</div></li></ul><p><b>Pathogenic variants.</b> See <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a> for information on other <i>GALT</i> alleles.</p><p><b>Normal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b> The normal human GALT protein contains 379 amino acids and functions as a homodimer with two active sites [<a class="bk_pop" href="#duarte-gal.REF.wedekind.1995.11049">Wedekind et al 1995</a>, <a class="bk_pop" href="#duarte-gal.REF.holden.2003.43885">Holden et al 2003</a>].</p><p>A <i>GALT</i> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> with only the c.940A>G (p.Asn314Asp) variant is thought to produce a fully functional protein (reviewed in <a class="bk_pop" href="#duarte-gal.REF.carney.2009.1624">Carney et al [2009]</a>).</p><p><b>Abnormal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b> Abnormal gene products associated with different pathogenic alleles of <i>GALT</i> are described in <a href="/books/n/gene/galactosemia/">Classic Galactosemia and Clinical Variant Galactosemia</a>.</p></div></div><div id="duarte-gal.Chapter_Notes"><h2 id="_duarte-gal_Chapter_Notes_">Chapter Notes</h2><div id="duarte-gal.Acknowledgments"><h3>Acknowledgments</h3><p>The authors are grateful to their colleagues and to the many families affected by Duarte variant galactosemia who participate in research studies.</p></div><div id="duarte-gal.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>25 June 2020 (AA) Revision: added GALM deficiency and associated references</div></li><li class="half_rhythm"><div>23 May 2019 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 December 2014 (me) Review posted live</div></li><li class="half_rhythm"><div>20 May 2014 (jfk) Original submission</div></li></ul></div></div><div id="duarte-gal.References"><h2 id="_duarte-gal_References_">References</h2><div id="duarte-gal.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.badik.2011.469">Badik JR, Castañeda U, Gleason T, Spencer J, Epstein M, Ficicioglu C, Fitzgerald K, Fridovich-Keil J. Ovarian function in Duarte galactosemia. <span><span class="ref-journal">Fertil Steril. </span>2011;<span class="ref-vol">96</span>:469–73.e1.</span> [<a href="/pmc/articles/PMC3773175/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3773175</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21719007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21719007</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.bernard.2012.273">Bernard O, Franchi-Abella S, Branchereau S, Pariente D, Gauthier F, Jacquemin E. Congenital portosystemic shunts in children: recognition, evaluation, and management. <span><span class="ref-journal">Semin Liver Dis. </span>2012;<span class="ref-vol">32</span>:273–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23397528" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23397528</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.carlock.2019.e20182516">Carlock G, Fischer ST, Lynch ME, Potter NL, Coles CD, Epstein MP, Mulle JG, Kable JA, Barrett CE, Edwards SM, Wilson E, Fridovich-Keil JL. Developmental outcomes in Duarte galactosemia. <span><span class="ref-journal">Pediatrics. </span>2019;<span class="ref-vol">143</span>:e20182516. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30593450" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30593450</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.carney.2009.1624">Carney AE, Sanders RD, Garza KR, McGaha LA, Bean LJ, Coffee BW, Thomas JW, Cutler DJ, Kurtkaya NL, Fridovich-Keil JL. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase. <span><span class="ref-journal">Hum Mol Genet. </span>2009;<span class="ref-vol">18</span>:1624–32.</span> [<a href="/pmc/articles/PMC2667289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2667289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19224951" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19224951</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.fernhoff.2010.1045">Fernhoff PM. Duarte galactosemia: how sweet is it? <span><span class="ref-journal">Clin Chem. </span>2010;<span class="ref-vol">56</span>:1045–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20489130" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20489130</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.ficicioglu.2010.1177">Ficicioglu C, Hussa C, Gallagher PR, Thomas N, Yager C. Monitoring of biochemical status in children with Duarte galactosemia: utility of galactose, galactitol, galactonate, and galactose 1-phosphate. <span><span class="ref-journal">Clin Chem. </span>2010;<span class="ref-vol">56</span>:1177–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20489133" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20489133</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.ficicioglu.2008.206">Ficicioglu C, Thomas N, Yager C, Gallagher PR, Hussa C, Mattie A, Day-Salvatore DL, Forbes BJ. Duarte (DG) galactosemia: a pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening. <span><span class="ref-journal">Mol Genet Metab. </span>2008;<span class="ref-vol">95</span>:206–12.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18976948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18976948</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.fridovichkeil.2019.2683">Fridovich-Keil JL, Carlock G, Coles CD, Lynch ME, Millians MN, Potter NL, Powell K, Richards P, Singh R, Wittenauer A. Developmental outcomes of children with Duarte galactosemia: exploring the bases of an apparent contradiction in the literature. <span><span class="ref-journal">Genet Med. </span>2019;<span class="ref-vol">21</span>:2683–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31160755" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31160755</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.holden.2003.43885">Holden HM, Rayment I, Thoden JB. Structure and function of enzymes of the Leloir pathway for galactose metabolism. <span><span class="ref-journal">J Biol Chem. </span>2003;<span class="ref-vol">278</span>:43885–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12923184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12923184</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.iwasawa.2019.362">Iwasawa S, Kikuchi A, Wada Y, Arai-Ichinoi N, Sakamoto O, Tamiya G, Kure S. The prevalence of GALM mutations that cause galactosemia: A database of functionally evaluated variants. <span><span class="ref-journal">Mol Genet Metab. </span>2019;<span class="ref-vol">126</span>:362–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30910422" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30910422</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.mccandless.2019.e20183292">McCandless SE. Answering a question older than most pediatricians: what to do about Duarte variant galactosemia. <span><span class="ref-journal">Pediatrics. </span>2019;<span class="ref-vol">143</span>:e20183292. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30593448" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30593448</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.palmieri.1999.1294">Palmieri M, Mazur A, Berry GT, Ning C, Wehrli S, Yager C, Reynolds R, Singh R, Muralidharan K, Langley S, Elsas L 2nd, Segal S. Urine and plasma galactitol in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia. <span><span class="ref-journal">Metabolism. </span>1999;<span class="ref-vol">48</span>:1294–302.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10535394" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10535394</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.powell.2009.874">Powell KK, Van Naarden Braun K, Singh RH, Shapira SK, Olney RS, Yeargin-Allsopp M. Long-term speech and language developmental issues among children with Duarte galactosemia. <span><span class="ref-journal">Genet Med. </span>2009;<span class="ref-vol">11</span>:874–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19904210" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19904210</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.pyhtila.2015.79">Pyhtila BM, Shaw KA, Neumann SE, Fridovich-Keil JL. Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead. <span><span class="ref-journal">JIMD Rep. </span>2015;<span class="ref-vol">15</span>:79–93.</span> [<a href="/pmc/articles/PMC4413015/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4413015</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24718839" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24718839</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.wada.2019.1286">Wada Y, Kikuchi A, Arai-Ichinoi N, Sakamoto O, Takezawa Y, Iwasawa S, Niihori T, Nyuzuki H, Nakajima Y, Ogawa E, Ishige M, Hirai H, Sasai H, Fujiki R, Shirota M, Funayama R, Yamamoto M, Ito T, Ohara O, Nakayama K, Aoki Y, Koshiba S, Fukao T, Kure S. Biallelic GALM pathogenic variants cause a novel type of galactosemia. <span><span class="ref-journal">Genet Med. </span>2019;<span class="ref-vol">21</span>:1286–94.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30451973" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30451973</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.walter.2014">Walter JH, Fridovich-Keil JL. Galactosemia. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. <em>The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID).</em> Chap 72. New York, NY: McGraw-Hill. 2014.</div></li><li class="half_rhythm"><div class="bk_ref" id="duarte-gal.REF.wedekind.1995.11049">Wedekind JE, Frey PA, Rayment I. Three-dimensional structure of galactose-1-phosphate uridylyltransferase from escherichia coli at 1.8A resolution. <span><span class="ref-journal">Biochemistry. </span>1995;<span class="ref-vol">34</span>:11049–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7669762" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7669762</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK258640/?report=reader">PubReader</a></li><li><a href="/books/NBK258640/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK258640" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK258640" style="display:none" title="Cite this Page"><div class="bk_tt">Fridovich-Keil JL, Gambello MJ, Singh RH, et al. Duarte Variant Galactosemia. 2014 Dec 4 [Updated 2020 Jun 25]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK258640/pdf/Bookshelf_NBK258640.pdf">PDF version of this page</a> (468K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#duarte-gal.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#duarte-gal.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#duarte-gal.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#duarte-gal.Genetically_Related_Allelic_D" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#duarte-gal.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#duarte-gal.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#duarte-gal.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#duarte-gal.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#duarte-gal.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#duarte-gal.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#duarte-gal.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Classic Galactosemia and Clinical Variant Galactosemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Classic Galactosemia and Clinical Variant Galactosemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Berry GT. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21290786" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" 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class="invert">Review</span> Citrullinemia Type I.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Citrullinemia Type I.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Quinonez SC, Lee KN. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301497" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Biotinidase Deficiency.</a><span 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