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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Free Sialic Acid Storage Disorders" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2020/01/23" /><meta name="citation_author" content="David Adams" /><meta name="citation_author" content="Melissa Wasserstein" /><meta name="citation_pmid" content="20301643" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1470/" /><meta name="citation_keywords" content="Infantile Free Sialic Acid Storage Disease (ISSD)" /><meta name="citation_keywords" content="Salla Disease" /><meta name="citation_keywords" content="Sialin" /><meta name="citation_keywords" content="SLC17A5" /><meta name="citation_keywords" content="Free Sialic Acid Storage Disorders" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Free Sialic Acid Storage Disorders" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="David Adams" /><meta name="DC.Contributor" content="Melissa Wasserstein" /><meta name="DC.Date" content="2020/01/23" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1470/" /><meta name="description" content="Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. 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Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. 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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="#__NBK1470_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1470_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/fhs/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/friedreich/" 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="_NBK1470_"><span class="title" itemprop="name">Free Sialic Acid Storage Disorders</span></h1><p class="contrib-group"><span itemprop="author">David Adams</span>, MD, PhD and <span itemprop="author">Melissa Wasserstein</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK1470_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1470_ai__"><div class="contrib half_rhythm"><span itemprop="author">David Adams</span>, MD, PhD<div class="affiliation small">National Human Genome Research Institute<br />National Institutes of Health<br />Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.liam@1smadad" class="oemail">vog.hin.liam@1smadad</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Melissa Wasserstein</span>, MD<div class="affiliation small">Albert Einstein College of Medicine<br />Children’s Hospital at Montefiore<br />Bronx, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.eroifetnom@sressawm" class="oemail">gro.eroifetnom@sressawm</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">June 13, 2003</span>; Last Update: <span itemprop="dateModified">January 23, 2020</span>.</p><p><em>Estimated reading time: 24 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="issd.Summary" itemprop="description"><h2 id="_issd_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific <a class="def" href="/books/n/gene/glossary/def-item/founder-variant/">founder variant</a> is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of a FSASD 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>SLC17A5</i> on <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>: Management is symptomatic and supportive: standard treatment of seizures; feeding therapy and provision of adequate nutrition; rehabilitation to optimize mobility and communication; supplementation of calcium and vitamin D for low bone density; family and social support.</p><p><i>Surveillance</i>: Assessment of feeding, respiratory status, seizures, development, mobility, and nutrition with each visit. Regular evaluation by a rehabilitation specialist to identify potentially helpful interventions. Annual EKG and echocardiography for cardiomegaly.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>The FSASDs are 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. Molecular genetic <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> for at-risk relatives, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for pregnancies at increased risk, and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible if the pathogenic variants in the family are known.</p></div></div><div id="issd.GeneReview_Scope"><h2 id="_issd_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div id="issd.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Free Sialic Acid Storage Disorders: Included Phenotypes <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_issd.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Salla disease</div></li><li class="half_rhythm"><div>Infantile free sialic acid storage disease (ISSD)</div></li></ul>
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</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">For synonyms and outdated names see <a href="#issd.Nomenclature">Nomenclature</a>.</p></div></dd></dl></div></div></div></div><div id="issd.Diagnosis"><h2 id="_issd_Diagnosis_">Diagnosis</h2><p>There are no consensus clinical diagnostic criteria for free sialic acid storage disorders (FSASDs).</p><div id="issd.Suggestive_Findings"><h3>Suggestive Findings</h3><p>A FSASD <b>should be suspected/considered</b> in individuals with the following clinical, imaging, and laboratory findings.</p><div id="issd.Less_Severe_FSASD_Including_Salla_D"><h4>Less Severe FSASD Including Salla Disease</h4><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Truncal ataxia and hypotonia apparent at approximately one year of age</div></li><li class="half_rhythm"><div>Developmental delay</div></li><li class="half_rhythm"><div>Growth deficiency (short stature)</div></li><li class="half_rhythm"><div>Intellectual disability</div></li><li class="half_rhythm"><div>Spasticity</div></li><li class="half_rhythm"><div>Facial coarsening (variable and not always present)</div></li></ul><p>
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<b>Imaging findings on brain MRI examination</b>
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</p><ul><li class="half_rhythm"><div>Hypomyelination of the basal ganglia</div></li><li class="half_rhythm"><div>Hypoplasia of the corpus callosum</div></li></ul></div><div id="issd.Severe_FSASD_Including_Infantile_Fr"><h4>Severe FSASD Including Infantile Free Sialic Acid Storage Disease (ISSD)</h4><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Nonimmune hydrops fetalis (24%)</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li><li class="half_rhythm"><div>Failure to thrive</div></li><li class="half_rhythm"><div>Severe developmental delay</div></li><li class="half_rhythm"><div>Cardiomegaly</div></li><li class="half_rhythm"><div>Club feet</div></li><li class="half_rhythm"><div>Increasingly coarse facial features</div></li><li class="half_rhythm"><div>Neurologic deterioration</div></li><li class="half_rhythm"><div>Early death</div></li></ul><p><b>Imaging findings on skeletal survey (ISSD)</b> include skeletal dysostosis (e.g., irregular enlarged metaphyses, short femurs, diffuse hypomineralization with fractures, hip dysplasia, anterior beaking of the dorsal vertebrae, and hypoplasia of the distal phalanges).</p></div><div id="issd.FSASD_Including_Less_Severe_and_Sev"><h4>FSASD Including Less Severe and Severe Forms</h4><p>
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<b>Laboratory findings</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Free sialic acid.</b> Sialic acids are a family of negatively charged sugars, one of which, N-acetylneuraminic acid, is elevated in lysosomes in free sialic acid storage disorders.</div><div class="half_rhythm">Urinary excretion of free sialic acid, measured by the fluorimetric thiobarbituric acid assay, thin-layer chromatography or mass spectrometry, is elevated about tenfold in individuals with Salla disease and about 100-fold in individuals with ISSD. HPLC/tandem mass spectrometry is also able to detect free sialic acid in urine [<a class="bk_pop" href="#issd.REF.valianpour.2004.403">Valianpour et al 2004</a>].</div><div class="half_rhythm">Note: (1) In the thiobarbituric acid assay, interfering substances may lower the measurement and chromophores may contribute to absorbance, creating a false measurement. (2) In thin-layer chromatography, an elevation of free sialic acid may be overlooked.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Cultured fibroblasts</b> from individuals with all forms of FSASD show increased concentration of free sialic acid [<a class="bk_pop" href="#issd.REF.renlund.1986.759">Renlund et al 1986</a>].</div></li></ul></div></div><div id="issd.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of a free sialic acid storage disorder <b>is established</b> 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 (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>SLC17A5</i> on <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1470/table/issd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobissdTmoleculargenetictestingusedin">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="#issd.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>SLC17A5</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>SLC17A5</i> pathogenic variant and one <i>SLC17A5</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Because the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of free sialic acid storage disorders is broad, individuals with the distinctive findings described in <a href="#issd.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#issd.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other inherited neurodegenerative disorders are more likely to be diagnosed using genomic testing (see <a href="#issd.Option_2">Option 2</a>).</p><div id="issd.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of free sialic acid storage disorders, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></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>SLC17A5</i> detects <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-gene deletions/duplications are not detected. Perform <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> first. If only one or no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect intragenic deletions or duplications.</div><div class="half_rhythm">Note: Targeted analysis for <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a> can be performed first in individuals of Finnish or Swedish ancestry [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>].</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>SLC17A5</i> and other genes of interest (see <a href="#issd.Differential_Diagnosis">Differential Diagnosis</a>) 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>. 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>. Of note, given the rarity of free sialic acid storage disorders some panels for developmental delay may not include this gene. (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. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK1470/table/issd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobissdTmoleculargenetictestingusedin">Table 1</a>).</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></ul></div><div id="issd.Option_2"><h4>Option 2</h4><p>When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other inherited disorders characterized by neurodegeneration, <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (which does not require the clinician to predetermine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>[s] are likely involved) is the best option. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>If <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> is not diagnostic, <b><a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a></b> (when clinically available) may be considered to detect (multi)<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</p><p>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>.</p><div id="issd.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Free Sialic Acid Storage Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.molecular_genetic_testing_used_in_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_issd.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_issd.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC17A5</i>
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</td><td headers="hd_h_issd.T.molecular_genetic_testing_used_in_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_issd.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%-95% <sup>4, 5</sup></td></tr><tr><td headers="hd_h_issd.T.molecular_genetic_testing_used_in_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>6</sup></td><td headers="hd_h_issd.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5%-10% <sup>4, 7</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="issd.TF.1.1"><p class="no_margin">See <a href="/books/NBK1470/#issd.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="issd.TF.1.2"><p class="no_margin">See <a href="#issd.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="issd.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="issd.TF.1.4"><p class="no_margin">The <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a> variant, known as the "FIN" variant, is common in the Finnish and other Nordic populations; therefore, a higher detection rate by sequencing is expected in those populations [<a class="bk_pop" href="#issd.REF.peltonen.1999.1913">Peltonen et al 1999</a>, <a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>].</p></div></dd><dt>5. </dt><dd><div id="issd.TF.1.5"><p class="no_margin"><a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al [2000]</a>, <a class="bk_pop" href="#issd.REF.froissart.2005.829">Froissart et al [2005]</a>, <a class="bk_pop" href="#issd.REF.zielonka.2019.347">Zielonka et al [2019]</a></p></div></dd><dt>6. </dt><dd><div id="issd.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> 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>7. </dt><dd><div id="issd.TF.1.7"><p class="no_margin"><a class="bk_pop" href="#issd.REF.tarailograovac.2017.28">Tarailo-Graovac et al [2017]</a>, <a class="bk_pop" href="#issd.REF._igman.2018.1155">Žigman et al [2018]</a></p></div></dd></dl></div></div></div></div></div></div><div id="issd.Clinical_Characteristics"><h2 id="_issd_Clinical_Characteristics_">Clinical Characteristics</h2><div id="issd.Clinical_Description"><h3>Clinical Description</h3><p>To date, approximately 80 individuals have been identified with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>SLC17A5</i> [<a class="bk_pop" href="#issd.REF.alajoki.2004.832">Alajoki et al 2004</a>, <a class="bk_pop" href="#issd.REF.zielonka.2019.347">Zielonka et al 2019</a>]. (~300 individuals with free sialic acid storage disorders [FSASDs] are reported in the literature, but many reports do not include molecular data.) The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="issd.T.select_features_of_free_sialic_ac" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of Free Sialic Acid Storage Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.select_features_of_free_sialic_ac/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.select_features_of_free_sialic_ac_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Feature <sup>1</sup></th><th id="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental delay / cognitive impairment</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">75%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Facial dysmorphism / coarse facies <sup>2</sup></td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%-68% <sup>2</sup></td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hepatosplenomegaly</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">54%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Truncal hypotonia</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">54%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Skeletal abnormalities</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Spasticity</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">48%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ataxia</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">44%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Failure to thrive</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">42%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Short stature</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hydrops fetalis</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">24%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Epilepsy</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Neurodegenerative course</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Neonatal ascites</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cardiomegaly</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hernias</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Microcephaly</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Recurrent airway infections</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nystagmus</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nephropathy</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Optic atrophy</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Athetosis</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ptosis</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hoarse voice</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Corneal clouding</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI findings</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain atrophy</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypomyelination</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22%</td></tr><tr><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypoplasia of the corpus callosum</td><td headers="hd_h_issd.T.select_features_of_free_sialic_ac_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16%</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Adapted from <a class="bk_pop" href="#issd.REF.zielonka.2019.347">Zielonka et al [2019]</a></p></div></dd><dt>1. </dt><dd><div id="issd.TF.2.1"><p class="no_margin">Includes features reported in entire spectrum of <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> (less severe to severe FSASD)</p></div></dd><dt>2. </dt><dd><div id="issd.TF.2.2"><p class="no_margin">Coarse facies are more frequent in severe FSASD.</p></div></dd></dl></div></div></div><p>The FSASDs comprise a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). Salla disease was named for a municipality in Finnish Lapland where a specific <a class="def" href="/books/n/gene/glossary/def-item/founder-variant/">founder variant</a> is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD in general. Less severe FSASD is characterized by normal appearance and neurologic findings at birth followed by slowly progressive neurologic deterioration resulting in mild to moderate psychomotor delay, spasticity, athetosis, and epileptic seizures. More severe FSASD, also known as ISSD, is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.</p><div id="issd.Less_Severe_FSASD_Salla_Disease"><h4>Less Severe FSASD (Salla Disease)</h4><p>Salla disease, which serves as a model for less severe FSASD, has the mildest <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> [<a class="bk_pop" href="#issd.REF.varho.2002.267">Varho et al 2002</a>]. It is characterized by a normal appearance and normal neurologic findings at birth followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delay [<a class="bk_pop" href="#issd.REF.renlund.1983.57">Renlund et al 1983</a>, <a class="bk_pop" href="#issd.REF.alajoki.2004.832">Alajoki et al 2004</a>]. Muscular hypotonia is often first recognized at approximately age six months. One third of affected children learn to walk. Expressive language development can be limited to single words but receptive speech is good. Slow developmental progress often continues until the third decade, after which regression can occur.</p><p>Some individuals with Salla disease present later in life with spasticity, athetosis, and epileptic seizures, becoming nonambulatory and nonverbal. Affected individuals are characterized as good-humored and sociable [<a class="bk_pop" href="#issd.REF.varho.2002.267">Varho et al 2002</a>].</p><p>T<sub>2</sub>-weighted bright cerebral white matter changes on brain MRI are typical but variable. Abnormal myelination of the basal ganglia and hypoplasia of the corpus callosum are constant and early findings [<a class="bk_pop" href="#issd.REF.sonninen.1999.433">Sonninen et al 1999</a>]. Cerebellar white matter changes are also present and can explain the ataxia [<a class="bk_pop" href="#issd.REF.linnankivi.2003.107">Linnankivi et al 2003</a>, <a class="bk_pop" href="#issd.REF.biancheri.2004.587">Biancheri et al 2004</a>]. In addition to the central dysmyelination, a peripheral dysmyelination with the clinical picture of a polyneuropathy occurs with variable neurologic presentations [<a class="bk_pop" href="#issd.REF.varho.2000.99">Varho et al 2000</a>, <a class="bk_pop" href="#issd.REF.varho.2002.267">Varho et al 2002</a>].</p><p>Affected individuals do not have organomegaly, skeletal dysostosis, or abnormal eye findings. Growth hormone and gonadotropin deficiencies were observed in one individual [<a class="bk_pop" href="#issd.REF.grosso.2001.775">Grosso et al 2001</a>].</p><p>Life expectancy appears to be shortened, although affected individuals up to age 72 years have been observed.</p></div><div id="issd.Intermediate_Severe_FSASD"><h4>Intermediate Severe FSASD</h4><p>Since the advent of molecular studies, phenotypes with a severity between those of Salla disease and ISSD [<a class="bk_pop" href="#issd.REF.aula.2001">Aula & Gahl 2001</a>] have been attributed to compound heterozygosity for the Salla disease-causing common <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a> and another <i>SLC17A5</i> pathogenic variant [<a class="bk_pop" href="#issd.REF.kleta.2003.28">Kleta et al 2003</a>]. Thus, the term "intermediate severe Salla disease" was proposed [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>].</p></div><div id="issd.Severe_FSASD_Infantile_Free_Sialic"><h4>Severe FSASD (Infantile Free Sialic Acid Storage Disease; ISSD)</h4><p>ISSD, the most severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly. Additional reported features include early truncal hypotonia with later spasticity and ataxia, skeletal abnormalities, and seizures (see <a href="/books/NBK1470/table/issd.T.select_features_of_free_sialic_ac/?report=objectonly" target="object" rid-ob="figobissdTselectfeaturesoffreesialicac">Table 2</a>). No single feature occurs in all individuals.</p><p>ISSD can present prenatally and in the neonatal period with nonimmune hydrops fetalis (24% of individuals) [<a class="bk_pop" href="#issd.REF.lemyre.1999.385">Lemyre et al 1999</a>, <a class="bk_pop" href="#issd.REF.stone.1999.409">Stone & Sidransky 1999</a>, <a class="bk_pop" href="#issd.REF.froissart.2005.829">Froissart et al 2005</a>, <a class="bk_pop" href="#issd.REF.zielonka.2019.347">Zielonka et al 2019</a>]. Some affected infants are born prematurely. Other affected infants appear normal at birth but lose developmental milestones during infancy [<a class="bk_pop" href="#issd.REF.kleta.2003.28">Kleta et al 2003</a>, <a class="bk_pop" href="#issd.REF.kleta.2004.137">Kleta et al 2004</a>].</p><p>Skeletal abnormalities can include irregular metaphyses, diffuse hypomineralization, club feet, short femurs, enlarged metaphyses, fractures, hip dysplasia, anterior beaking of the dorsal vertebrae, and hypoplasia of the distal phalanges [<a class="bk_pop" href="#issd.REF.froissart.2005.829">Froissart et al 2005</a>].</p><p>Dysmorphic facial features are nonspecific and generally fall into the spectrum of "coarsened" features (e.g., epicanthal folds, ptosis, anteverted nose, gum hypertrophy).</p><p>Reported ocular findings include nystagmus, exotropia, optic atrophy, and albinoid fundi. Corneal clouding has been rarely reported.</p><p>Additional reported features include nephropathy and/or nephrotic syndrome and hernias [<a class="bk_pop" href="#issd.REF.lemyre.1999.385">Lemyre et al 1999</a>, <a class="bk_pop" href="#issd.REF.ishiwari.2004.656">Ishiwari et al 2004</a>].</p><p>Death usually occurs in early childhood, typically from recurrent respiratory infections.</p></div></div><div id="issd.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Correlations between the type of <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and the severity of the lysosomal free sialic acid storage disease have been identified [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>, <a class="bk_pop" href="#issd.REF.varho.2000.99">Varho et al 2000</a>, <a class="bk_pop" href="#issd.REF.kleta.2003.28">Kleta et al 2003</a>]:</p><ul><li class="half_rhythm"><div>Homozygosity for the pathogenic <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a>, a single Finnish <a class="def" href="/books/n/gene/glossary/def-item/founder-variant/">founder variant</a>, leads to Salla disease, with its slow clinical course of neurologic deterioration.</div></li><li class="half_rhythm"><div>Compound heterozygosity for the p.Arg39Cys <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and another <i>SLC17A5</i> pathogenic variant leads to intermediate severe FSASD, as does homozygosity for the <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Lys136Glu</a> pathogenic variant [<a class="bk_pop" href="#issd.REF.biancheri.2005.195">Biancheri et al 2005</a>].</div></li><li class="half_rhythm"><div>Compound heterozygosity for pathogenic variants other than <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a> leads to the severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of FSASD (ISSD), with early onset and multisystemic involvement.</div></li></ul><p>Variable expression has been observed among affected family members [<a class="bk_pop" href="#issd.REF.landau.2004.167">Landau et al 2004</a>].</p></div><div id="issd.Penetrance"><h3>Penetrance</h3><p>The FSASDs appear to be fully penetrant. However, <a class="bk_pop" href="#issd.REF.mochel.2009.753">Mochel et al [2009]</a> reported two individuals with <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Lys136Glu</a> pathogenic variants, no detectable urinary sialic acid abnormality, and elevated CSF free sialic acid, suggesting that <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> based on urinary studies alone may be incomplete.</p></div><div id="issd.Nomenclature"><h3>Nomenclature</h3><p>Free sialic acid storage disorders (FSASDs) have been and continue to be labeled with different terms, mainly because of the different names used to denote N-acetylneuraminic acid. The term free sialic acid storage disorder refers to the entire spectrum of disease. The form of less severe FSASD historically known as Salla disease is specific to the Finnish founder mutation, but continues to be used colloquially to refer to mild forms of FSASD. Severe, infantile onset ISSD remains in usage to refer to disease at the more severe end of the FSASD spectrum.</p></div><div id="issd.Prevalence"><h3>Prevalence</h3><p>Less severe FSASD (Salla disease), has been reported in approximately 150 individuals, mainly from Finland and Sweden [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>, <a class="bk_pop" href="#issd.REF.erikson.2002.1324">Erikson et al 2002</a>]. Individuals with molecularly proven less severe FSASD have been identified outside of Finland and Sweden [<a class="bk_pop" href="#issd.REF.martin.2003.23">Martin et al 2003</a>]. The prevalence of the <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object" rid-ob="figobissdTnotableslc17a5pathogenicvarian">p.Arg39Cys</a> is high in the founder region of northeastern Finland, where the <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequency is in the range of 1:100 [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>]. Ninety-five percent of individuals of Finnish descent with FSASD have the p.Arg39Cys pathogenic variant. The prevalence of other <i>SLC17A5</i> pathogenic variants appears to be independent of the geographic origin or ethnicity of affected individuals; their presence has been documented in more than 30 individuals from several countries throughout the world [<a class="bk_pop" href="#issd.REF.lemyre.1999.385">Lemyre et al 1999</a>, <a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>, <a class="bk_pop" href="#issd.REF.kleta.2003.28">Kleta et al 2003</a>, <a class="bk_pop" href="#issd.REF.martin.2003.23">Martin et al 2003</a>, <a class="bk_pop" href="#issd.REF.s_nderby_christensen.2003.1357">Sønderby Christensen et al 2003</a>, <a class="bk_pop" href="#issd.REF.kleta.2004.137">Kleta et al 2004</a>].</p></div></div><div id="issd.Genetically_Related_Allelic_Disorde"><h2 id="_issd_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>SLC17A5</i>.</p></div><div id="issd.Differential_Diagnosis"><h2 id="_issd_Differential_Diagnosis_">Differential Diagnosis</h2><div id="issd.Biochemical_Findings"><h3>Biochemical Findings</h3><p><b>Increased urinary and cellular free sialic acid.</b> The only disorders in which significantly elevated urinary and cellular free sialic acid are known to occur are sialuria (OMIM <a href="https://omim.org/entry/269921" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">269921</a>) and the free sialic acid storage disorders (Salla disease and ISSD). The clinical course of sialuria involves developmental delay and hepatomegaly but does not include severe neurologic involvement or early death. In sialuria, elevation of free sialic acid occurs in the cytoplasm rather than in the lysosome.</p><p>Based on clinical suspicion and the finding of elevated free sialic acid in urine, one of two steps is taken to distinguish these conditions:</p><ul><li class="half_rhythm"><div>The cellular (cytoplasmic versus lysosomal) localization of free sialic acid can be documented; a predominantly lysosomal localization indicates a FSASD.</div></li><li class="half_rhythm"><div>Molecular genetic testing of <i>SLC17A5</i> (for FSASD) or <i>GNE</i> (for sialuria) can be performed.</div></li></ul><p>Note: Other causes of mild elevation in urinary free sialic acid may exist.</p><p><b>Sialic acid bound to glycoproteins or glycolipids.</b> If sialic acid bound to glycoproteins or glycolipids is stored, disorders such as sialidosis caused by sialidase (neuraminidase) deficiency (OMIM <a href="https://omim.org/entry/256550" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">256550</a>) and galactosialidosis (OMIM <a href="https://omim.org/entry/256540" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">256540</a>) caused by combined sialidase and galactosidase deficiency should be considered (see <a href="/books/NBK1470/table/issd.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobissdTothergenesofinterestinthedi">Table 3</a>). These enzyme deficiencies involve lysosomal storage of sialic acid-containing glycoconjugates. These disorders both have features typical of lysosomal storage diseases, but they vary widely in their manifestations.</p></div><div id="issd.Clinical_Findings"><h3>Clinical Findings</h3><p>See <a href="/books/NBK1470/table/issd.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobissdTothergenesofinterestinthedi">Table 3</a> for other lysosomal storage disorders that are associated with the clinical manifestation of coarse facial features and developmental delays and other causes of nonimmune hydrops fetalis. Note: All disorders included in <a href="/books/NBK1470/table/issd.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobissdTothergenesofinterestinthedi">Table 3</a> are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p><div id="issd.T.other_genes_of_interest_in_the_di" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Other Genes of Interest in the Differential Diagnosis of Free Sialic Acid Storage Disorders (FSASDs)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.other_genes_of_interest_in_the_di_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Finding(s) Overlapping w/FSASDs</th><th id="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Associated Enzyme</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_1" rowspan="9" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Coarse facial features & developmental delays</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>AGA</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/agu/">Aspartylglucosaminuria</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ARSB</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS VI (OMIM <a href="https://omim.org/entry/253200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">253200</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arylsulfastase B</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FUCA1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fucosidosis (OMIM <a href="https://omim.org/entry/230000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">230000</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tissue alpha-L-fucosidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GLB1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GM1 gangliosidosis (See <a href="/books/n/gene/gm1-ganglio/"><i>GLB1</i>-Related Disorders</a>.)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beta-galactosidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GNPTAB</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mucolipidosis II (I-cell disease) (See <a href="/books/n/gene/ml2/"><i>GNPTAB</i>-Related Disorders</a>.)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-acetylglucosamine-1-phosphotransferase subunits alpha/beta</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>IDS</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/hunter/">MPS II</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Iduronate 2-sulfatase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>IDUA</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/mps1/">MPS I</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alpha-L-iduronidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MAN2B1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/a-mannosidosis/">Alpha-mannosidosis</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lysosomal alpha-mannosidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NEU1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sialidosis type II (OMIM <a href="https://omim.org/entry/256550" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">256550</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sialidase-1</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_1" rowspan="10" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Nonimmune hydrops fetalis</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CTSA</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Galactosialidosis (OMIM <a href="https://omim.org/entry/256540" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">256540</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lysosomal protective protein</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GALC</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/krabbe/">Krabbe disease</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Galactocerebrosidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><i>GBA1</i> (<i>GBA</i>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/gaucher/">Gaucher disease</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lysosomal acid glucosylceramidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GBA2</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beta-glucosidase deficiency (OMIM <a href="https://omim.org/entry/614409" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614409</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Non-lysosomal glucosylceramidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GNPTAB</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">I-cell disease (<a href="/books/n/gene/ml2/">Mucolipidosis II</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-acetylglucosamine-1-phosphotransferase subunits alpha/beta</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GUSB</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/mps7/">MPS VII</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beta-glucuronidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>IDUA</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/mps1/">MPS I</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alpha-L-iduronidase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>LIPA</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/lal-def/">Lysosomal acid lipase deficiency</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lysosomal acid lipase/cholesteryl ester hydrolase</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NEU1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sialidase deficiency (OMIM <a href="https://omim.org/entry/256550" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">256550</a>)</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sialidase-1</td></tr><tr><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SMPD1</i>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/npab/">Acid sphingomyelinase deficiency</a>
|
||
</td><td headers="hd_h_issd.T.other_genes_of_interest_in_the_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sphingomyelin phosphodiesterase</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">From Saudubray & Charpentier, Chapter 86, Table 42, <a href="https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225079473" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><i>Online Metabolic and Molecular Bases of Inherited Disease</i></a>. Accessed 8-23-22 (Registration required).</p></div></dd><dt></dt><dd><div><p class="no_margin">MPS = mucopolysaccharidosis</p></div></dd></dl></div></div></div></div></div><div id="issd.Management"><h2 id="_issd_Management_">Management</h2><div id="issd.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a free sialic acid storage disorder, the evaluations summarized in <a href="/books/NBK1470/table/issd.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobissdTrecommendedevaluationsfollowing">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="issd.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Free Sialic Acid Storage Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl brain MRI</div></li><li class="half_rhythm"><div>Consider EEG if seizures are a concern.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech-language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.recommended_evaluations_following_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_issd.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
|
||
<ul><li class="half_rhythm"><div>Gross motor & fine motor skills;</div></li><li class="half_rhythm"><div>Mobility, activities of daily living, & need for adaptive devices;</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills).</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/</b>
|
||
<br />
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of aspiration risk & nutritional status</div></li><li class="half_rhythm"><div>Consider eval for gastrostomy tube placement in those w/dysphagia &/or aspiration risk.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Miscellaneous/</b>
|
||
<br />
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biochemical genetics or neurogenetics consultation</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a></td></tr><tr><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Family support & resources</td><td headers="hd_h_issd.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#issd.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></div></div></div></div><div id="issd.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>The medical and psychosocial management of individuals with free sialic acid storage disorders is symptomatic and supportive.</p><div id="issd.T.treatment_of_manifestations_in_in" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Free Sialic Acid Storage Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.treatment_of_manifestations_in_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.treatment_of_manifestations_in_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Epilepsy</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for FSASDs.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD/ID</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#issd.Developmental_Delay__Intellectual_D">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Poor weight gain /</b>
|
||
<br />
|
||
<b>Failure to thrive</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding therapy; gastrostomy tube placement may be required for persistent feeding issues.</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia</td></tr><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Spasticity</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT incl stretching to help avoid contractures & falls</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider need for positioning & mobility devices, disability parking placard.</td></tr><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Low bone density /</b>
|
||
<br />
|
||
<b>Fractures</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Supplementation as necessary to provide adequate calcium & vitamin D intake</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/</b>
|
||
<br />
|
||
<b>Community</b>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
|
||
</td><td headers="hd_h_issd.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or <a href="https://www.specialolympics.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Special Olympics</a>.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication; DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="issd.TF.5.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div><div id="issd.Developmental_Delay__Intellectual_D"><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 as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</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 for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child’s IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child’s access to academic material. Beyond that, private supportive therapies based on the affected individual’s needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US 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 id="issd.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li><li class="half_rhythm"><div>For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox<sup>®</sup>, anti-parkinsonian medications, or orthopedic procedures.</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction</b> should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically by an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.</p></div></div><div id="issd.Surveillance"><h3>Surveillance</h3><div id="issd.T.recommended_surveillance_for_indi" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Free Sialic Acid Storage Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.recommended_surveillance_for_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.recommended_surveillance_for_indi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_issd.T.recommended_surveillance_for_indi_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_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measurement of growth parameters</div></li><li class="half_rhythm"><div>Eval of nutritional status & safety of oral intake</div></li></ul>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Respiratory</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for evidence of aspiration, respiratory insufficiency.</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor those w/seizures as clinically indicated.</div></li><li class="half_rhythm"><div>Assess for new manifestations (e.g., seizures, changes in tone, mvmt disorders).</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical medicine &/or rehab medicine, OT/PT assessment of mobility, self-help skills</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Nutritional monitoring incl vitamin D intake</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiomegaly</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">EKG & echocardiography</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually for signs of cardiomegaly</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Nephrotic</b>
|
||
<br />
|
||
<b>syndrome</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urinalysis for protein</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td><td headers="hd_h_issd.T.recommended_surveillance_for_indi_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></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></div></div></div></div><div id="issd.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>No routine testing of apparently asymptomatic at-risk family members is recommended because adult presentations are unusual and no early interventions are available.</p><p>See <a href="#issd.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="issd.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="issd.Genetic_Counseling"><h2 id="_issd_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="issd.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>The free sialic acid storage disorders are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="issd.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., presumed to be carriers of one <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment. (<i>De</i>
|
||
<i>novo</i> variants are known to occur at a low but appreciable rate in <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> disorders [<a class="bk_pop" href="#issd.REF.j_nsson.2017.519">Jónsson et al 2017</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>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception 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. Variable expression has been observed among affected sibs [<a class="bk_pop" href="#issd.REF.landau.2004.167">Landau et al 2004</a>].</div></li><li class="half_rhythm"><div>Heterozygotes 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> Because of the severity of the disease, affected individuals are unlikely 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>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="issd.Carrier_Detection"><h3>Carrier Detection</h3><p><b>Molecular genetic testing.</b> Carrier testing for at-risk relatives requires prior identification of the <i>SLC17A5</i> pathogenic variants in the family.</p><p><b>Biochemically</b> based <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> is not feasible.</p></div><div id="issd.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 young adults who are carriers or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Because the prevalence of the <i>SLC17A5</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> p.Arg39Cys is high in the founder region of northeastern Finland (where the <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequency is in the range of 1:100; see <a href="/books/n/gene/founder_finnish/">Genetic Disorders Associated with Founder Variants Common in the Finnish Population</a>), pre-conception testing of the partner of a known carrier may be requested if the partner is of Finnish descent.</div></li></ul></div><div id="issd.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the 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 <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="issd.Resources"><h2 id="_issd_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>Salla Treatment and Research (STAR) Foundation</b>
|
||
</div><div>
|
||
<a href="https://www.star-foundation.io/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">star-foundation.io</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Metabolic Support UK</b>
|
||
</div><div>United Kingdom</div><div><b>Phone:</b> 0845 241 2173</div><div>
|
||
<a href="https://metabolicsupportuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">metabolicsupportuk.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Tay-Sachs and Allied Diseases Association (NTSAD)</b>
|
||
</div><div><b>Phone:</b> 617-277-4463</div><div><b>Email:</b> info@ntsad.org</div><div>
|
||
<a href="https://www.ntsad.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ntsad.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Myelin Disorders Bioregistry Project</b>
|
||
</div><div><b>Phone:</b> 215-590-1719</div><div><b>Email:</b> sherbinio@chop.edu</div><div>
|
||
<a href="https://www.chop.edu/research/myelin-disorders-biorepository-project" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Myelin Disorders Bioregistry Project</a>
|
||
</div></li></ul>
|
||
</div><div id="issd.Molecular_Genetics"><h2 id="_issd_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="issd.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Free Sialic Acid Storage Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_issd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_issd.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_issd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_issd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_issd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_issd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/26503" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>SLC17A5</i>
|
||
</a>
|
||
</td><td headers="hd_b_issd.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=26503" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">6q13</a>
|
||
</td><td headers="hd_b_issd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q9NRA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Sialin</a>
|
||
</td><td headers="hd_b_issd.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=SLC17A5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SLC17A5</a>
|
||
</td><td headers="hd_b_issd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SLC17A5[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SLC17A5</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="issd.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="issd.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Free Sialic Acid Storage Disorders (<a href="/omim/269920,604322,604369" 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/NBK1470/table/issd.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/269920" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">269920</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INFANTILE SIALIC ACID STORAGE DISEASE; ISSD</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/604322" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604322</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SOLUTE CARRIER FAMILY 17 (ACIDIC SUGAR TRANSPORTER), MEMBER 5; SLC17A5</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/604369" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604369</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SALLA DISEASE; SD</td></tr></tbody></table></div></div><p>The <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a> of <i>SLC17A5</i>, sialin, is an integral lysosomal membrane transporter that exports free sialic acid from lysosomes [<a class="bk_pop" href="#issd.REF.mancini.1991.1329">Mancini et al 1991</a>]. Deficient or defective sialin results in excessive lysosomal storage of the free sialic acid produced by lysosomal degradation of glycoproteins and glycolipids. How elevated intralysosomal free sialic acid causes pathology is not understood. Expression of sialin in the brain may explain part of the neurologic sequelae of Salla disease/ISSD [<a class="bk_pop" href="#issd.REF.aula.2004.251">Aula et al 2004</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div id="issd.T.notable_slc17a5_pathogenic_varian" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>SLC17A5</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1470/table/issd.T.notable_slc17a5_pathogenic_varian/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__issd.T.notable_slc17a5_pathogenic_varian_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_012434.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_012434<wbr style="display:inline-block"></wbr>.4</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&id=6912666" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_036566<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.115C>T</td><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg39Cys</td><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Finnish & other Nordic populations [<a class="bk_pop" href="#issd.REF.aula.2000.832">Aula et al 2000</a>]</td></tr><tr><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.406A>G</td><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Lys136Glu</td><td headers="hd_h_issd.T.notable_slc17a5_pathogenic_varian_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Penetrance may be incomplete in some <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> individuals [<a class="bk_pop" href="#issd.REF.mochel.2009.753">Mochel et al 2009</a>].</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div><div id="issd.Chapter_Notes"><h2 id="_issd_Chapter_Notes_">Chapter Notes</h2><div id="issd.Author_Notes"><h3>Author Notes</h3><p>David Adams, MD, PhD is a pediatrician, medical geneticist, and biochemical geneticist who performs clinical and basic research into rare diseases at the National Institutes of Health.</p></div><div id="issd.Author_History"><h3>Author History</h3><p>David Adams, MD, PhD (2008-present)<br />William A Gahl, MD, PhD; National Human Genome Research Institute (2003-2020)<br />Robert Kleta, MD, PhD; National Human Genome Research Institute (2003-2008)<br />Melissa Wasserstein, MD (2020-present)</p></div><div id="issd.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>23 January 2020 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 June 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>3 July 2008 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 October 2005 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>13 June 2003 (ca) Review posted live</div></li><li class="half_rhythm"><div>28 February 2003 (wg) Original submission</div></li></ul></div></div><div id="issd.References"><h2 id="_issd_References_">References</h2><div id="issd.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="issd.REF.alajoki.2004.832">Alajoki
|
||
L, Varho
|
||
T, Posti
|
||
K, Aula
|
||
P, Korhonen
|
||
T.
|
||
Neurocognitive profiles in Salla disease.
|
||
Dev Med Child Neurol.
|
||
2004;46:832-7.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15581157" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15581157</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="issd.REF.aula.2004.251">Aula
|
||
N, Kopra
|
||
O, Jalanko
|
||
A, Peltonen
|
||
L. Sialin expression in the CNS implicates extralysosomal function in neurons.
|
||
Neurobiol Dis.
|
||
2004;15:251-61.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15006695" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15006695</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="issd.REF.aula.2000.832">Aula
|
||
N, Salomäki
|
||
P, Timonen
|
||
R, Verheijen
|
||
F, Mancini
|
||
G, Mansson
|
||
JE, Aula
|
||
P, Peltonen
|
||
L. The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation.
|
||
Am J Hum Genet
|
||
2000;67:832-40.
|
||
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1470/?report=reader">PubReader</a></li><li><a href="/books/NBK1470/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1470" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1470" style="display:none" title="Cite this Page"><div class="bk_tt">Adams D, Wasserstein M. Free Sialic Acid Storage Disorders. 2003 Jun 13 [Updated 2020 Jan 23]. 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