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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Asparagine Synthetase Deficiency" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2018/09/20" /><meta name="citation_author" content="Majid Alfadhel" /><meta name="citation_author" content="Ayman W El-Hattab" /><meta name="citation_pmid" content="30234940" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK525916/" /><meta name="citation_keywords" content="ASNS Deficiency" /><meta name="citation_keywords" content="ASNS Deficiency" /><meta name="citation_keywords" content="Asparagine synthetase [glutamine-hydrolyzing]" /><meta name="citation_keywords" content="ASNS" /><meta name="citation_keywords" content="Asparagine Synthetase Deficiency" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Asparagine Synthetase Deficiency" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Majid Alfadhel" /><meta name="DC.Contributor" content="Ayman W El-Hattab" /><meta name="DC.Date" content="2018/09/20" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK525916/" /><meta name="description" content="Asparagine synthetase deficiency (ASD) mainly presents as a triad of congenital microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low cerebrospinal fluid (CSF) asparagine level can help the clinician in differentiating this disorder from others. In most cases age of onset of apnea, excessive irritability, and seizures is soon after birth. Affected individuals typically do not acquire any developmental milestones. Spastic quadriplegia can lead to severe contractures of the limbs and neurogenic scoliosis. Feeding difficulties (gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination) are a significant problem in most affected individuals. A majority have cortical blindness. MRI findings are nonspecific but may include generalized atrophy and simplified gyral pattern." /><meta name="og:title" content="Asparagine Synthetase Deficiency" /><meta name="og:type" content="book" /><meta name="og:description" content="Asparagine synthetase deficiency (ASD) mainly presents as a triad of congenital microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low cerebrospinal fluid (CSF) asparagine level can help the clinician in differentiating this disorder from others. In most cases age of onset of apnea, excessive irritability, and seizures is soon after birth. Affected individuals typically do not acquire any developmental milestones. Spastic quadriplegia can lead to severe contractures of the limbs and neurogenic scoliosis. Feeding difficulties (gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination) are a significant problem in most affected individuals. 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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="#__NBK525916_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK525916_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/mld/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/agu/" 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="_NBK525916_"><span class="title" itemprop="name">Asparagine Synthetase Deficiency</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: ASNS Deficiency</div><p class="contrib-group"><span itemprop="author">Majid Alfadhel</span>, MD, HHSc, SSC-Ped, ABHS(CH), FCCMG and <span itemprop="author">Ayman W El-Hattab</span>, MD, FAAP, FACMG.</p><a data-jig="ncbitoggler" href="#__NBK525916_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK525916_ai__"><div class="contrib half_rhythm"><span itemprop="author">Majid Alfadhel</span>, MD, HHSc, SSC-Ped, ABHS(CH), FCCMG<div class="affiliation small">Genetics Division, Department of Pediatrics<br />King Saud Bin Abdulaziz University for Health Sciences<br />King Abdulaziz Medical City<br />Riyadh, Saudi Arabia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@mlehdaflard" class="oemail">moc.liamg@mlehdaflard</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ayman W El-Hattab</span>, MD, FAAP, FACMG<div class="affiliation small">Associate Professor, Department of Clinical Sciences<br />College of Medicine<br />University of Sharjah<br />Sharjah, United Arab Emirates<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.oohay@wabattahle" class="oemail">moc.oohay@wabattahle</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 20, 2018</span>.</p><p><em>Estimated reading time: 15 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="as-def.Summary" itemprop="description"><h2 id="_as-def_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Asparagine synthetase deficiency (ASD) mainly presents as a triad of <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low cerebrospinal fluid (CSF) asparagine level can help the clinician in differentiating this disorder from others. In most cases age of onset of apnea, excessive irritability, and seizures is soon after birth. Affected individuals typically do not acquire any developmental milestones. Spastic quadriplegia can lead to severe contractures of the limbs and neurogenic scoliosis. Feeding difficulties (gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination) are a significant problem in most affected individuals. A majority have cortical blindness. MRI findings are nonspecific but may include generalized atrophy and simplified gyral pattern.</p></div><div><h4 class="inline">Diagnosis.</h4><p>The diagnosis of ASD is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> by identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>ASNS</i> by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Antispastic medication (baclofen, tizanidine, and/or Botox<sup>®</sup> injection) for spasticity; clonazepam for hyperekplexia; mechanical ventilation may be required for apnea; nasogastric or gastrostomy tube to support nutrition; standard treatment for seizures, hearing loss, gastroesophageal reflux disease, constipation, and kyphosis/scoliosis; supportive developmental therapies.</p><p><i>Prevention of secondary complications:</i> Regular immunization to prevent life-threatening infections.</p><p>
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<i>Surveillance</i>
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</p><ul><li class="half_rhythm"><div>At each visit: evaluation of developmental progress and growth; assessment for progression of spasticity, contractures, and scoliosis/kyphosis.</div></li><li class="half_rhythm"><div>Every six months: assessment of nutritional status through serum total protein, albumin, and prealbumin levels.</div></li><li class="half_rhythm"><div>Annually: ophthalmologic evaluation.</div></li><li class="half_rhythm"><div>As needed: EEG if there are concerns for new-onset seizure activity or progression of seizures; audiologic evaluation if there are concerns for hearing loss.</div></li></ul></div><div><h4 class="inline">Genetic counseling.</h4><p>Asparagine synthetase deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk are possible if the <i>ASNS</i> pathogenic variants in the family are known.</p></div></div><div id="as-def.Diagnosis"><h2 id="_as-def_Diagnosis_">Diagnosis</h2><div id="as-def.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Asparagine synthetase deficiency (ASD) <b>should be suspected</b> in individuals with the following clinical features, brain MRI findings, and supportive laboratory findings.</p><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div>Congenital and progressive microcephaly</div></li><li class="half_rhythm"><div>Severe global developmental delay</div></li><li class="half_rhythm"><div>Hypotonia followed by spastic quadriplegia, seizures, jitteriness, and hyperekplexia</div></li><li class="half_rhythm"><div>Intrauterine growth restriction with subsequent feeding difficulties, failure to thrive, and short stature</div></li><li class="half_rhythm"><div>Cortical blindness</div></li></ul><p>
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<b>Brain MRI findings</b>
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</p><ul><li class="half_rhythm"><div>Generalized brain atrophy (100%)</div></li><li class="half_rhythm"><div>Simplified gyral pattern (81%)</div></li><li class="half_rhythm"><div>Cerebellar vermis hypoplasia (41%)</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div><b>CSF asparagine level</b> is typically low or not detected [<a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>].</div></li><li class="half_rhythm"><div><b>Plasma asparagine level</b> is low in about half of affected individuals and is not as sensitive as CSF asparagine levels in supporting this diagnosis.</div></li><li class="half_rhythm"><div><b>The following</b> are unremarkable:</div><ul><li class="half_rhythm"><div>Plasma acylcarnitine profile</div></li><li class="half_rhythm"><div>Creatine kinase (CK) level</div></li><li class="half_rhythm"><div>Total homocysteine, lactic acid, and ammonia levels</div></li><li class="half_rhythm"><div>Urine organic acids</div></li></ul></li></ul></div><div id="as-def.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of ASD <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>ASNS</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK525916/table/as-def.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobasdefTmoleculargenetictestingused">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#as-def.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>ASNS</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>ASNS</i> pathogenic variant and one <i>ASNS</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b>, use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>, and <b>more comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>ASNS</i> is performed first and followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> if only one or no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>ASNS</i> and other genes of interest (see <a href="#as-def.Differential_Diagnosis">Differential Diagnosis</a>) may be considered. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>More comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (when available) including <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> and <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a> may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> or genes that results in a similar clinical presentation).</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div id="as-def.T.molecular_genetic_testing_used" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Asparagine Synthetase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.molecular_genetic_testing_used/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.molecular_genetic_testing_used_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ASNS</i>
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</td><td headers="hd_h_as-def.T.molecular_genetic_testing_used_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_as-def.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22/22 <sup>4</sup></td></tr><tr><td headers="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_as-def.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="as-def.TF.1.1"><p class="no_margin">See <a href="/books/NBK525916/#as-def.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="as-def.TF.1.2"><p class="no_margin">See <a href="#as-def.Molecular_Genetics">Molecular Genetics</a> for information on 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="as-def.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 <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 and small intragenic deletions/insertions; 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="as-def.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al [2013]</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al [2015]</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al [2015]</a>, <a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al [2015]</a>, <a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al [2016]</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al [2016]</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al [2017]</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al [2017]</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al [2017]</a></p></div></dd><dt>5. </dt><dd><div id="as-def.TF.1.5"><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 range of techniques such as <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>6. </dt><dd><div id="as-def.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> has not identified any pathogenic variants to date.</p></div></dd></dl></div></div></div></div></div><div id="as-def.Clinical_Characteristics"><h2 id="_as-def_Clinical_Characteristics_">Clinical Characteristics</h2><div id="as-def.Clinical_Description"><h3>Clinical Description</h3><p>Asparagine synthetase deficiency (ASD) mainly presents as a triad of <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low CSF asparagine level can help differentiate this disorder from others with similar clinical findings [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>]. Age of onset is soon after birth in the majority of reported individuals (median age of onset: 1 day; range 1 day – 9 months). Only three cases have presented after the neonatal period [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.sacharow.2018.317">Sacharow et al 2018</a>]. Two neonates presented prenatally with microcephaly detected by antenatal ultrasound [<a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>].</p><p>The common clinical manifestations summarized in <a href="/books/NBK525916/table/as-def.T.clinical_manifestations_of_22_i/?report=objectonly" target="object" rid-ob="figobasdefTclinicalmanifestationsof22i">Table 2</a> are discussed below the table.</p><div id="as-def.T.clinical_manifestations_of_22_i" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Clinical Manifestations of 22 Individuals with Asparagine Synthetase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.clinical_manifestations_of_22_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.clinical_manifestations_of_22_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical Manifestations</th><th id="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Frequency (%)</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neonatal onset <sup>1</sup></td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17/18 (95%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe global developmental delay</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22/22 (100%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital & progressive microcephaly <sup>2</sup></td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22/22 (100%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperreflexia</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22/22 (100%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Axial hypotonia followed by spastic quadriplegia</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21/22 (95%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizures</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16/22 (73%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Jitteriness</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/15 (87%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cortical blindness</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/22 (60%)</td></tr><tr><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperekplexia</td><td headers="hd_h_as-def.T.clinical_manifestations_of_22_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/22 (32%)</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="as-def.TF.2.1"><p class="no_margin">Congenital microcephaly, apnea, excessive irritability, and seizures</p></div></dd><dt>2. </dt><dd><div id="as-def.TF.2.2"><p class="no_margin">Head circumference is often 2 standard deviations (SD) below the mean at birth but may decline to 9 SD below the mean by early childhood.</p></div></dd></dl></div></div></div><p><b>Neurologic.</b> All affected individuals reported have the following:</p><ul><li class="half_rhythm"><div>Congenital microcephaly, ranging between 26.5 and 33.4 cm (1-4 SD below the mean)</div></li><li class="half_rhythm"><div>Severe global developmental delay with no acquisition of developmental milestones [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>]</div></li><li class="half_rhythm"><div>Axial hypotonia followed by spastic quadriplegia [<a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>] leading to severe contractures of all limbs and neurogenic scoliosis</div></li></ul><p><b>Seizures</b> usually start in the neonatal period and mimic pyridoxine-dependent epilepsy [<a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al 2016</a>].</p><ul><li class="half_rhythm"><div>The type of seizure is not specific and can include the following [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>]:</div><ul><li class="half_rhythm"><div>Generalized tonic-clonic (64%)</div></li><li class="half_rhythm"><div>Myoclonic (50%)</div></li><li class="half_rhythm"><div>Tonic (50%)</div></li><li class="half_rhythm"><div>Partial complex seizure (21%)</div></li><li class="half_rhythm"><div>Spasms (15%) that are refractory to anti-seizure medication</div></li></ul></li><li class="half_rhythm"><div>EEG abnormalities are nonspecific [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>, <a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al 2015</a>, <a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al 2016</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>]:</div><ul><li class="half_rhythm"><div>Multiple independent spike foci most commonly (65%)</div></li><li class="half_rhythm"><div>Burst suppression</div></li><li class="half_rhythm"><div>Hypsarrhythmia</div></li><li class="half_rhythm"><div>Discontinuous EEG pattern</div></li></ul></li><li class="half_rhythm"><div>Jitteriness and hyperekplexia are present in 78% and 35% of reported individuals, respectively.</div></li></ul><p><b>Brain MRI findings.</b> The most common features are summarized in <a href="#as-def.Suggestive_Findings">Suggestive Findings</a>; other reported abnormalities (in <80%) include the following [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>, <a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al 2016</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]:</p><ul><li class="half_rhythm"><div>Delayed myelination (68%)</div></li><li class="half_rhythm"><div>Small pons</div></li><li class="half_rhythm"><div>Thin corpus callosum (55%)</div></li><li class="half_rhythm"><div>Enlarged ventricular system (50%)</div></li><li class="half_rhythm"><div>Left transverse sinus thrombosis and cerebral dysgenesis</div></li><li class="half_rhythm"><div>Blake's cyst and/or arachnoid cyst</div></li><li class="half_rhythm"><div>Bilateral caudate atrophy</div></li><li class="half_rhythm"><div>Increased lactate peak on MR spectroscopy in four individuals studied [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al 2015</a>]</div></li></ul><p>Note: CSF asparagine level was normal in one reported individual [<a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>].</p><p><b>Nonspecific <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> facial features</b> reported in approximately 50% of affected individuals include brachycephaly, pear-like head shape, sloping forehead, widely spaced eyes, big fleshy ears, prominent nasal tip, and micrognathia.</p><p><b>Gastrointestinal manifestations.</b> Feeding difficulties are a major problem for most affected individuals. Contributing factors include hypotonia, gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination. Many affected individuals also have constipation.</p><p>Recurrent aspiration has been reported in eight individuals. Many require nasogastric tube feeding or gastrostomy [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>].</p><p><b>Ophthalmologic.</b> Most individuals are unable to fix and follow with their eyes. Cortical blindness is reported in 65% of affected individuals. One affected person was reported to have left convergent squint [<a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>].</p><p><b>Less frequently reported</b> manifestations include the following [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]:</p><ul><li class="half_rhythm"><div>Intrauterine growth restriction [<a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]</div></li><li class="half_rhythm"><div>Sensorineural hearing loss [<a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al 2015</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>]</div></li><li class="half_rhythm"><div>Frequent apneas necessitating mechanical ventilation, reported in nine affected individuals [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]</div></li><li class="half_rhythm"><div>Diaphragmatic eventration [<a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]</div></li><li class="half_rhythm"><div>Phrenic nerve palsy [<a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]</div></li></ul><p><b>Prognosis.</b> ASD is associated with a high rate of morbidity and mortality, where 50% of individuals die in the first year of life [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>]. However, because only a small cohort of affected individuals have been reported, it is possible that this represents the more severe end of a clinical spectrum.</p></div><div id="as-def.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been reported.</p></div><div id="as-def.Prevalence"><h3>Prevalence</h3><p>ASD has been reported in 22 individuals from 14 families to date. Consanguinity was reported in 50% of families. Affected individuals from Saudi Arabia, United Arab Emirates, Canada, France, Japan, and India have been reported [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>, <a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al 2015</a>, <a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al 2016</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>].</p></div></div><div id="as-def.Genetically_Related_Allelic_Disor"><h2 id="_as-def_Genetically_Related_Allelic_Disor_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with pathogenic variants in <i>ASNS</i>.</p></div><div id="as-def.Differential_Diagnosis"><h2 id="_as-def_Differential_Diagnosis_">Differential Diagnosis</h2><p>The differential diagnosis of ASD is wide, and the cardinal features of spastic quadriplegia, microcephaly, and low asparagine level can aid clinicians in differentiating this disorder from the other related disorders.</p><p>Note: Many chromosomal disorders present with features that overlap with asparagine synthetase deficiency; therefore, a <a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> could be considered.</p><div id="as-def.T.differential_diagnosis_of_aspar" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Differential Diagnosis of Asparagine Synthetase Deficiency (ASD)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.differential_diagnosis_of_aspar/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.differential_diagnosis_of_aspar_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" style="text-align:left;vertical-align:middle;">Phenotype/<br />Disorder</th><th id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" style="text-align:left;vertical-align:middle;">Gene(s) /<br />Genetic Mechanism</th><th id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of the Phenotype/Disorder</th></tr><tr><th headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4" id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/ASD</th><th headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4" id="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from ASD</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> microcephalies</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple genes (See OMIM <a href="https://omim.org/phenotypicSeries/PS251200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS251200</a>.)</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No malformations in other organ systems</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Normal CSF asparagine level</div></li><li class="half_rhythm"><div>No spastic quadriplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seckel syndrome</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATR</i><br /><i>CPAP</i> (<i>CENPJ</i>)<br /><i>CEP152</i><br /><i>CEP63</i><br /><i>RBBP8</i><br /><i>DNA2</i><br /><i>NIN</i><br /><i>NSMCE2</i><br /><i>TRAIP</i></td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Intrauterine growth restriction</div></li><li class="half_rhythm"><div>Sloping forehead</div></li><li class="half_rhythm"><div>Short stature</div></li></ul>
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</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Normal CSF asparagine level</div></li><li class="half_rhythm"><div>No spastic quadriplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lissencephaly-pachygyria <sup>1</sup></td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple genes (See OMIM <a href="https://omim.org/phenotypicSeries/PS607432" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS607432</a>.)</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD<br />XL</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cerebellar hypoplasia</div></li><li class="half_rhythm"><div>Simplified gyral pattern</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li></ul>
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</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lissencephaly & generalized polymicrogyria</div></li><li class="half_rhythm"><div>Normal CSF asparagine level</div></li></ul>
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</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Miller-Dieker syndrome<br />(See <a href="/books/n/gene/chrom17-lis/"><i>PAFAH1B1</i>-Associated Lissencephaly / Subcortical Band Heterotopia</a>.)</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17p13.3 <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a><br /><i>LIS1 (PAFAH1B1)</i><br /><i>YWHAE</i></td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Global DD</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li></ul>
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</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lissencephaly</div></li><li class="half_rhythm"><div>Dysmorphic features</div></li><li class="half_rhythm"><div>Normal CSF asparagine level</div></li></ul>
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</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/slo/">Smith-Lemli-Opitz syndrome</a>
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</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DHCR7</i>
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</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Global DD</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal & postnatal growth restriction</div></li><li class="half_rhythm"><div>Dysmorphic features</div></li><li class="half_rhythm"><div>Syndactyly of 2nd & 3rd toes</div></li><li class="half_rhythm"><div>Postaxial polydactyly</div></li><li class="half_rhythm"><div>Congenital heart defect</div></li><li class="half_rhythm"><div>Hypospadias in males</div></li><li class="half_rhythm"><div>No spastic quadriplegia</div></li><li class="half_rhythm"><div>Low total cholesterol w/↑ 7-dehydrocholesterol</div></li></ul>
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</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cdls/">Cornelia de Lange syndrome</a>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>HDAC8</i>
|
||
<br />
|
||
<i>NIPBL</i>
|
||
<br />
|
||
<i>RAD21</i>
|
||
<br />
|
||
<i>SMC1A</i>
|
||
<br />
|
||
<i>SMC3</i>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />XL</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Growth restriction</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li></ul>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Distinctive facial features</div></li><li class="half_rhythm"><div>Hirsutism</div></li><li class="half_rhythm"><div>Upper-limb reduction defects ranging from subtle phalangeal abnormalities to oligodactyly</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/serine-def/">Serine biosynthesis defects</a>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PHGDH</i>
|
||
<br />
|
||
<i>PSAT1</i>
|
||
<br />
|
||
<i>PSPH</i>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neonatal seizure</div></li><li class="half_rhythm"><div>Global DD</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li></ul>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Low CSF serine & glycine level</div></li><li class="half_rhythm"><div>Cataract</div></li><li class="half_rhythm"><div>Nystagmus</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cdg/">Congenital disorders of N-linked glycosylation</a>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple genes (See OMIM <a href="https://omim.org/phenotypicSeries/PS212065" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS212065</a>.)</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />XL</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neonatal seizure</div></li><li class="half_rhythm"><div>Failure to thrive</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li><li class="half_rhythm"><div>Cerebellar hypoplasia</div></li></ul>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hepatopathy</div></li><li class="half_rhythm"><div>Hypoglycemia</div></li><li class="half_rhythm"><div>Protein-losing enteropathy</div></li><li class="half_rhythm"><div>Eye abnormalities</div></li><li class="half_rhythm"><div>Immunologic findings</div></li><li class="half_rhythm"><div>Skin abnormalities</div></li><li class="half_rhythm"><div>Skeletal findings</div></li><li class="half_rhythm"><div>Abnormal TIF</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-infantile epileptic encephalopathy type 28</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>WWOX</i>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Congenital microcephaly</div></li><li class="half_rhythm"><div>Severe DD</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Spastic quadriplegia</div></li><li class="half_rhythm"><div>Thin corpus callosum</div></li><li class="half_rhythm"><div>Delayed myelination</div></li></ul>
|
||
</td><td headers="hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_1_4 hd_h_as-def.T.differential_diagnosis_of_aspar_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal blood & CSF asparagine level</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; CSF = cerebrospinal fluid; DD = developmental delay; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; TIF = transferrin isoelectrofocusing; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd><dt>1. </dt><dd><div id="as-def.TF.3.1"><p class="no_margin">Lissencephaly-pachygyria spectrum of cortical malformation is characterized by smooth cortex with simplified gyration appearance. "Lissencephaly" refers to a brain without sulci. Pachygyria (focal or diffuse) is a mild expression of lissencephaly in which sulci are shallow and reduced in number.</p></div></dd></dl></div></div></div></div><div id="as-def.Management"><h2 id="_as-def_Management_">Management</h2><div id="as-def.Evaluations_Following_Initial_Dia"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with asparagine synthetase deficiency (ASD), the following evaluations are recommended if they have not already been completed.</p><div id="as-def.T.recommended_evaluations_followi" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis of Asparagine Synthetase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.recommended_evaluations_followi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.recommended_evaluations_followi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI to evaluate extent of disease</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider neurologic consultation.</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">EEG</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If seizures are suspected</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider visual evoked potential.</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/</b>
|
||
<br />
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of growth parameters to identify those w/failure to thrive</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment for feeding problems incl difficulty w/sucking, swallowing, & GERD</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to feeding therapist if feeding problems identified</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical eval for scoliosis &/or kyphosis</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider radiographic scoliosis survey (radiographs of the spine) based on clinical suspicion; consider referral to orthopedist if scoliosis is present.</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To provide a baseline level of functioning & recommendations for services (speech, occupational, physical therapy)</td></tr><tr><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Consider referral to clinical geneticist &/or genetic counselor.</td><td headers="hd_h_as-def.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">GERD = gastroesophageal reflux</p></div></dd></dl></div></div></div></div><div id="as-def.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>The management of ASD requires a multidisciplinary team approach; treatment is primarily supportive.</p><p>Note: Asparagine supplementation has not been effective and actually exacerbated seizures in affected individuals [<a class="bk_pop" href="#as-def.REF.alrifai.2016.98">Alrifai & Alfadhel 2016</a>].</p><div id="as-def.T.treatment_of_manifestations_in" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Asparagine Synthetase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.treatment_of_manifestations_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.treatment_of_manifestations_in_lrgtbl__"><table><thead><tr><th id="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Manifestation/Concern</th><th id="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment</th><th id="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment w/anti-seizure medication</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Spastic quadriplegia</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Antispastic drugs (e.g., baclofen, tizanidine) &/or Botox<sup>®</sup> injection</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hyperekplexia</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clonazepam appears to be the most effective treatment.</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing aids</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/n/gene/deafness-overview/">Hereditary Hearing Loss and Deafness Overview</a>.</td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Apnea</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mechanical ventilation may be required.</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Inadequate nutrition /</b>
|
||
<br />
|
||
<b>Feeding difficulties</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nasogastric tube or gastrostomy tube is frequently required.</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastroesophageal</b>
|
||
<br />
|
||
<b>reflux (GERD)</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard pharmacologic treatment</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For severe GERD: consider Nissen fundoplication at the time of gastrostomy tube placement.</td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constipation</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Kyphosis/Scoliosis</b>
|
||
</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment as recommended by orthopedist</td><td headers="hd_h_as-def.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div><div id="as-def.Gross_Motor_Dysfunction"><h4>Gross Motor Dysfunction</h4><p>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</p><p>Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</p><p>For muscle tone abnormalities including hypertonia, consider involving appropriate specialists to aid in management of baclofen, Botox<sup>®</sup>, or orthopedic procedures.</p></div><div id="as-def.Developmental_Delay__Intellectual"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.</p><p>Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</p><p>In the US:</p><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div></div><div id="as-def.Prevention_of_Secondary_Complicat"><h3>Prevention of Secondary Complications</h3><p>Regular immunization to prevent life-threatening infections is indicated.</p></div><div id="as-def.Surveillance"><h3>Surveillance</h3><div id="as-def.T.recommended_surveillance_for_in" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Asparagine Synthetase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.T.recommended_surveillance_for_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.T.recommended_surveillance_for_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of developmental progress</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment for progression of spasticity & contractures</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">EEG</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If concerns for new seizure activity or progression of seizures</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If concern for hearing loss</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/</b>
|
||
<br />
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of growth parameters</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Eval of nutritional status <sup>1</sup></td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6 mos</td></tr><tr><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for scoliosis/kyphosis</td><td headers="hd_h_as-def.T.recommended_surveillance_for_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="as-def.TF.6.1"><p class="no_margin">Serum total protein, albumin, and prealbumin levels</p></div></dd></dl></div></div></div></div><div id="as-def.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#as-def.Related_Genetic_Counseling_Issues">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="as-def.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 access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="as-def.Genetic_Counseling"><h2 id="_as-def_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<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
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="as-def.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Asparagine synthetase deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="as-def.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<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>The parents of an affected child are obligate heterozygotes (i.e., carriers of one <i>ASNS</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> To date, individuals affected with asparagine synthetase deficiency are not known to reproduce.</p><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> of an <i>ASNS</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="as-def.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ASNS</i> pathogenic variants in the family.</p></div><div id="as-def.Related_Genetic_Counseling_Issues"><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 the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>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 the parents of an affected child.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#as-def.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="as-def.Prenatal_Testing_and_Preimplantat"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ASNS</i> pathogenic variants have been identified in an affected family member, prenatal 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 prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a>. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="as-def.Resources"><h2 id="_as-def_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>American Association on Intellectual and Developmental Disabilities (AAIDD)</b>
|
||
</div><div><b>Phone:</b> 202-387-1968</div><div>
|
||
<a href="https://www.aaidd.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aaidd.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>American Epilepsy Society</b>
|
||
</div><div>
|
||
<a href="https://www.aesnet.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aesnet.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Epilepsy Foundation</b>
|
||
</div><div><b>Phone:</b> 800-332-1000; 866-748-8008</div><div>
|
||
<a href="https://www.epilepsy.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.com</a>
|
||
</div></li></ul>
|
||
</div><div id="as-def.Molecular_Genetics"><h2 id="_as-def_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="as-def.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Asparagine Synthetase Deficiency: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK525916/table/as-def.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_as-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_as-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_as-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_as-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_as-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_as-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/440" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>ASNS</i>
|
||
</a>
|
||
</td><td headers="hd_b_as-def.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=440" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">7q21<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_b_as-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P08243" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Asparagine synthetase [glutamine-hydrolyzing]</a>
|
||
</td><td headers="hd_b_as-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ASNS" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ASNS</a>
|
||
</td><td headers="hd_b_as-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ASNS[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ASNS</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="as-def.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="as-def.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Asparagine Synthetase Deficiency (<a href="/omim/108370,615574" 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/NBK525916/table/as-def.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__as-def.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/108370" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">108370</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ASPARAGINE SYNTHETASE; ASNS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/615574" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">615574</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ASPARAGINE SYNTHETASE DEFICIENCY; ASNSD</td></tr></tbody></table></div></div><p><b>Gene structure.</b>
|
||
<i>ASNS</i> spans 35 kb and contains 13 exons. See <a href="/books/NBK525916/#as-def.molgen.TA">Table A</a>, <b>Gene</b> for a detailed summary of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> and protein information. <i>ASNS</i> is expressed in most mammalian cells. The gene was transcribed into an <a class="def" href="/books/n/gene/glossary/def-item/mrna/">mRNA</a> of 2 kb that was expressed in all human, hamster, and mouse cell lines tested. It encodes a protein of about 550 amino acids [<a class="bk_pop" href="#as-def.REF.greco.1987.1565">Greco et al 1987</a>].</p><p><b>Pathogenic variants.</b> Eighty-eight percent of reported pathogenic variants are <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>. Others include pathogenic <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> and frameshift variants [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>, <a class="bk_pop" href="#as-def.REF.bensalem.2015.687">Ben-Salem et al 2015</a>, <a class="bk_pop" href="#as-def.REF.palmer.2015.178">Palmer et al 2015</a>, <a class="bk_pop" href="#as-def.REF.gataullina.2016.399">Gataullina et al 2016</a>, <a class="bk_pop" href="#as-def.REF.seidahmed.2016.105">Seidahmed et al 2016</a>, <a class="bk_pop" href="#as-def.REF.gupta.2017.1889">Gupta et al 2017</a>, <a class="bk_pop" href="#as-def.REF.sun.2017.1">Sun et al 2017</a>, <a class="bk_pop" href="#as-def.REF.yamamoto.2017.236">Yamamoto et al 2017</a>].</p><p><b>Normal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b>
|
||
<i>ASNS</i> encodes asparagine synthetase, which catalyzes the synthesis of asparagine from glutamine and aspartate [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>].</p><p><b>Abnormal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b>
|
||
<i>ASNS</i> pathogenic variants result in loss of enzyme function, which in turn results in impaired synthesis of asparagine. Insufficient physiologic levels of arginine cause neurologic impairment [<a class="bk_pop" href="#as-def.REF.ruzzo.2013.429">Ruzzo et al 2013</a>, <a class="bk_pop" href="#as-def.REF.alfadhel.2015.11">Alfadhel et al 2015</a>].</p></div><div id="as-def.Chapter_Notes"><h2 id="_as-def_Chapter_Notes_">Chapter Notes</h2><div id="as-def.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>20 September 2018 (mpa) Review posted live</div></li><li class="half_rhythm"><div>8 January 2018 (ma) Original submission</div></li></ul></div></div><div id="as-def.References"><h2 id="_as-def_References_">References</h2><div id="as-def.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.alfadhel.2015.11">Alfadhel
|
||
M, Alrifai
|
||
MT, Trujillano
|
||
D, Alshaalan
|
||
H, Al Othaim
|
||
A, Al Rasheed
|
||
S, Assiri
|
||
H, Alqahtani
|
||
AA, Alaamery
|
||
M, Rolfs
|
||
A, Eyaid
|
||
W. Asparagine synthetase deficiency: new inborn errors of metabolism.
|
||
JIMD Rep.
|
||
2015;22:11-6.
|
||
[<a href="/pmc/articles/PMC4486270/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4486270</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25663424" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25663424</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.alrifai.2016.98">Alrifai
|
||
MT, Alfadhel
|
||
M. Worsening of seizures after asparagine supplementation in a child with asparagine synthetase deficiency.
|
||
Pediatr Neurol.
|
||
2016;58:98-100.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27268761" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27268761</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.bensalem.2015.687">Ben-Salem
|
||
S, Gleeson
|
||
JG, Al-Shamsi
|
||
AM, Islam
|
||
B, Hertecant
|
||
J, Ali
|
||
BR, Al-Gazali
|
||
L. Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay.
|
||
Metab Brain Dis.
|
||
2015;30:687-94
|
||
[<a href="/pmc/articles/PMC4915861/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4915861</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25227173" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25227173</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.gataullina.2016.399">Gataullina
|
||
S, Lauer-Zillhardt
|
||
J, Kaminska
|
||
A, Galmiche-Rolland
|
||
L, Bahi-Buisson
|
||
N, Pontoizeau
|
||
C, Ottolenghi
|
||
C, Dulac
|
||
O, Fallet-Bianco
|
||
C. Epileptic phenotype of two siblings with asparagine synthesis deficiency mimics neonatal pyridoxine-dependent epilepsy.
|
||
Neuropediatrics.
|
||
2016;47:399-403.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27522229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27522229</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.greco.1987.1565">Greco
|
||
A, Ittmann
|
||
M, Basilico
|
||
C. Molecular cloning of a gene that is necessary for G1 progression in mammalian cells.
|
||
Proc Natl Acad Sci U S A.
|
||
1987;84:1565-9.
|
||
[<a href="/pmc/articles/PMC304476/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC304476</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/3470743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3470743</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.gupta.2017.1889">Gupta
|
||
N, Tewari
|
||
VV, Kumar
|
||
M, Langeh
|
||
N, Gupta
|
||
A, Mishra
|
||
P, Kaur
|
||
P, Ramprasad
|
||
V, Murugan
|
||
S, Kumar
|
||
R, Jana
|
||
M, Kabra
|
||
M. Asparagine synthetase deficiency-report of a novel mutation and review of literature.
|
||
Metab Brain Dis.
|
||
2017;32:1889-900
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28776279" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28776279</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.huang.2022.389">Huang
|
||
SJ, Amendola
|
||
LM, Sternen
|
||
DL. Variation among DNA banking consent forms: points for clinicians to bank on.
|
||
J Community Genet.
|
||
2022;13:389-97.
|
||
[<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.palmer.2015.178">Palmer
|
||
EE, Hayner
|
||
J, Sachdev
|
||
R, Cardamone
|
||
M, Kandula
|
||
T, Morris
|
||
P, Dias
|
||
KR, Tao
|
||
J, Miller
|
||
D, Zhu
|
||
Y, Macintosh
|
||
R, Dinger
|
||
ME, Cowley
|
||
MJ, Buckley
|
||
MF, Roscioli
|
||
T, Bye
|
||
A, Kilberg
|
||
MS, Kirk
|
||
EP. Asparagine synthetase deficiency causes reduced proliferation of cells under conditions of limited asparagine.
|
||
Mol Genet Metab.
|
||
2015;116:178-86.
|
||
[<a href="/pmc/articles/PMC10152381/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10152381</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26318253" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26318253</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.richards.2015.405">Richards
|
||
S, Aziz
|
||
N, Bale
|
||
S, Bick
|
||
D, Das
|
||
S, Gastier-Foster
|
||
J, Grody
|
||
WW, Hegde
|
||
M, Lyon
|
||
E, Spector
|
||
E, Voelkerding
|
||
K, Rehm
|
||
HL, et al.
|
||
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
||
Genet Med.
|
||
2015;17:405-24.
|
||
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.ruzzo.2013.429">Ruzzo
|
||
EK, Capo-Chichi
|
||
JM, Ben-Zeev
|
||
B, Chitayat
|
||
D, Mao
|
||
H, Pappas
|
||
AL, Hitomi
|
||
Y, Lu
|
||
YF, Yao
|
||
X, Hamdan
|
||
FF, Pelak
|
||
K, Reznik-Wolf
|
||
H, Bar-Joseph
|
||
I, Oz-Levi
|
||
D, Lev
|
||
D, Lerman-Sagie
|
||
T, Leshinsky-Silver
|
||
E, Anikster
|
||
Y, Ben-Asher
|
||
E, Olender
|
||
T, Colleaux
|
||
L, Décarie
|
||
JC, Blaser
|
||
S, Banwell
|
||
B, Joshi
|
||
RB, He
|
||
XP, Patry
|
||
L, Silver
|
||
RJ, Dobrzeniecka
|
||
S, Islam
|
||
MS, Hasnat
|
||
A, Samuels
|
||
ME, Aryal
|
||
DK, Rodriguiz
|
||
RM, Jiang
|
||
YH, Wetsel
|
||
WC, McNamara
|
||
JO, Rouleau
|
||
GA, Silver
|
||
DL, Lancet
|
||
D, Pras
|
||
E, Mitchell
|
||
GA, Michaud
|
||
JL, Goldstein
|
||
DB. Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.
|
||
Neuron.
|
||
2013;80:429-41.
|
||
[<a href="/pmc/articles/PMC3820368/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3820368</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24139043" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24139043</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.sacharow.2018.317">Sacharow
|
||
SJ, Dudenhausen
|
||
EE, Lomelino
|
||
CL, Rodan
|
||
L, El Achkar
|
||
CM, Olson
|
||
HE, Genetti
|
||
CA, Agrawal
|
||
PB, McKenna
|
||
R, Kilberg
|
||
MS. Characterization of a novel variant in siblings with asparagine synthetase deficiency.
|
||
Mol Genet Metab.
|
||
2018;123:317-25.
|
||
[<a href="/pmc/articles/PMC5832599/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5832599</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29279279" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29279279</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.seidahmed.2016.105">Seidahmed
|
||
MZ, Salih
|
||
MA, Abdulbasit
|
||
OB, Samadi
|
||
A, Al Hussien
|
||
K, Miqdad
|
||
AM, Biary
|
||
MS, Alazami
|
||
AM, Alorainy
|
||
IA, Kabiraj
|
||
MM, Shaheen
|
||
R, Alkuraya
|
||
FS. Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report.
|
||
BMC Neurol.
|
||
2016;16:105.
|
||
[<a href="/pmc/articles/PMC4947274/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4947274</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27422383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27422383</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.sun.2017.1">Sun
|
||
J, McGillivray
|
||
AJ, Pinner
|
||
J, Yan
|
||
Z, Liu
|
||
F, Bratkovic
|
||
D, Thompson
|
||
E, Wei
|
||
X, Jiang
|
||
H, Asan, Chopra M. Diaphragmatic eventration in sisters with asparagine synthetase deficiency: a novel homozygous ASNS mutation and expanded phenotype.
|
||
JIMD Rep.
|
||
2017;34:1-9
|
||
[<a href="/pmc/articles/PMC5509547/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5509547</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27469131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27469131</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="as-def.REF.yamamoto.2017.236">Yamamoto
|
||
T, Endo
|
||
W, Ohnishi
|
||
H, Kubota
|
||
K, Kawamoto
|
||
N, Inui
|
||
T, Imamura
|
||
A, Takanashi
|
||
JI, Shiina
|
||
M, Saitsu
|
||
H, Ogata
|
||
K, Matsumoto
|
||
N, Haginoya
|
||
K, Fukao
|
||
T. The first report of Japanese patients with asparagine synthetase deficiency.
|
||
Brain Dev.
|
||
2017;39:236-42.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27743885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27743885</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4614458" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=4614458" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301631" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Citrullinemia Type I.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Citrullinemia Type I.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Quinonez SC, Lee KN. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301570" ref="ordinalpos=1&linkpos=2&log$=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> Alpha-Mannosidosis.</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> Alpha-Mannosidosis.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Ficicioglu C, Stepien KM. </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=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Biotinidase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Biotinidase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Wolf B. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/25032271" ref="ordinalpos=1&linkpos=4&log$=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> Dihydrolipoamide Dehydrogenase Deficiency.</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> Dihydrolipoamide Dehydrogenase Deficiency.<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, Thoene JG. </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/28749637" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> SLC6A3-Related Dopamine Transporter Deficiency Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> SLC6A3-Related Dopamine Transporter Deficiency Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Spaull RVV, Kurian MA. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=30234940" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=30234940" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d2fdefcde49f3df71bbfdc">Asparagine Synthetase Deficiency - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Asparagine Synthetase Deficiency - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d2fdeecde49f3df71bba63">Table B. [OMIM Entries for Asparagine Synthetase Deficiency (View All in OMIM)]....</a><div class="ralinkpop offscreen_noflow">Table B. [OMIM Entries for Asparagine Synthetase Deficiency (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d2fdd12f30673f7b3ac29f">RecName: Full=Asparagine synthetase [glutamine-hydrolyzing]; AltName: Full=Cell ...</a><div class="ralinkpop offscreen_noflow">RecName: Full=Asparagine synthetase [glutamine-hydrolyzing]; AltName: Full=Cell cycle control protein TS11; AltName: Full=Glutamine-dependent asparagine synthetase<div class="brieflinkpopdesc">gi|13432102|sp|P08243.4|ASNS_HUMAN</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d2fdc084f3725e598647c8">CCZ1P1 CCZ1 pseudogene 1 [Homo sapiens]</a><div class="ralinkpop offscreen_noflow">CCZ1P1 CCZ1 pseudogene 1 [Homo sapiens]<div class="brieflinkpopdesc">Gene ID:110440226</div></div><div class="tertiary">Gene</div></li><li class="ra_qry two_line"><a class="htb" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d2fdbfcde49f3df71a6573">related_functional_gene_440[group] AND (alive[prop]) <span class="number">(7)</span></a><div class="tertiary">Gene</div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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